n-3 pufas deficiency: Topics by Science.gov

Sample records for n-3 pufas deficiency

Marginal Vitamin B-6 Deficiency Decreases Plasma (n-3) and (n-6) PUFA Concentrations in Healthy Men and Women123

PubMed Central

Zhao, Mei; Lamers, Yvonne; Ralat, Maria A.; Coats, Bonnie S.; Chi, Yueh-Yun; Muller, Keith E.; Bain, James R.; Shankar, Meena N.; Newgard, Christopher B.; Stacpoole, Peter W.; Gregory, Jesse F.

2012-01-01

Previous animal studies showed that severe vitamin B-6 deficiency altered fatty acid profiles of tissue lipids, often with an increase of linoleic acid and a decrease of arachidonic acid. However, little is known about the extent to which vitamin B-6 deficiency affects human fatty acid profiles. The aim of this study was to determine the effects of marginal vitamin B-6 deficiency on fatty acid profiles in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC) of healthy adults fed a 28-d, low-vitamin B-6 diet. Healthy participants (n = 23) received a 2-d, controlled, vitamin B-6–adequate diet followed by a 28-d, vitamin B-6–restricted diet to induce a marginal deficiency. Plasma HDL and LDL cholesterol concentrations, FFA concentrations, and erythrocyte and PBMC membrane fatty acid compositions did not significantly change from baseline after the 28-d restriction. Plasma total arachidonic acid, EPA, and DHA concentrations decreased from (mean ± SD) 548 ± 96 to 490 ± 94 μmol/L, 37 ± 13 to 32 ± 13 μmol/L, and 121 ± 28 to 109 ± 28 μmol/L [positive false discovery rate (pFDR) adjusted P < 0.05], respectively. The total (n-6):(n-3) PUFA ratio in plasma exhibited a minor increase from 15.4 ± 2.8 to 16.6 ± 3.1 (pFDR adjusted P < 0.05). These data indicate that short-term vitamin B-6 restriction decreases plasma (n-3) and (n-6) PUFA concentrations and tends to increase the plasma (n-6):(n-3) PUFA ratio. Such changes in blood lipids may be associated with the elevated risk of cardiovascular disease in vitamin B-6 insufficiency. PMID:22955512
Site-Specific Fat-1 Knock-In Enables Significant Decrease of n-6PUFAs/n-3PUFAs Ratio in Pigs

PubMed Central

Li, Mengjing; Ouyang, Hongsheng; Yuan, Hongming; Li, Jianing; Xie, Zicong; Wang, Kankan; Yu, Tingting; Liu, Minghao; Chen, Xue; Tang, Xiaochun; Jiao, Huping; Pang, Daxin

2018-01-01

The fat-1 gene from Caenorhabditis elegans encodes a fatty acid desaturase which was widely studied due to its beneficial function of converting n-6 polyunsaturated fatty acids (n-6PUFAs) to n-3 polyunsaturated fatty acids (n-3PUFAs). To date, many fat-1 transgenic animals have been generated to study disease pathogenesis or improve meat quality. However, all of them were generated using a random integration method with variable transgene expression levels and the introduction of selectable marker genes often raise biosafety concern. To this end, we aimed to generate marker-free fat-1 transgenic pigs in a site-specific manner. The Rosa26 locus, first found in mouse embryonic stem cells, has become one of the most common sites for inserting transgenes due to its safe and ubiquitous expression. In our study, the fat-1 gene was inserted into porcine Rosa 26 (pRosa26) locus via Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. The Southern blot analysis of our knock-in pigs indicated a single copy of the fat-1 gene at the pRosa26 locus. Furthermore, this single-copy fat-1 gene supported satisfactory expression in a variety of tissues in F1 generation pigs. Importantly, the gas chromatography analysis indicated that these fat-1 knock-in pigs exhibited a significant increase in the level of n-3PUFAs, leading to an obvious decrease in the n-6PUFAs/n-3PUFAs ratio from 9.36 to 2.12 (***P < 0.0001). Altogether, our fat-1 knock-in pigs hold great promise for improving the nutritional value of pork and serving as an animal model to investigate therapeutic effects of n-3PUFAs on various diseases. PMID:29563188
Site-Specific Fat-1 Knock-In Enables Significant Decrease of n-6PUFAs/n-3PUFAs Ratio in Pigs.

PubMed

Li, Mengjing; Ouyang, Hongsheng; Yuan, Hongming; Li, Jianing; Xie, Zicong; Wang, Kankan; Yu, Tingting; Liu, Minghao; Chen, Xue; Tang, Xiaochun; Jiao, Huping; Pang, Daxin

2018-05-04

The fat-1 gene from Caenorhabditis elegans encodes a fatty acid desaturase which was widely studied due to its beneficial function of converting n-6 polyunsaturated fatty acids (n-6PUFAs) to n-3 polyunsaturated fatty acids (n-3PUFAs). To date, many fat-1 transgenic animals have been generated to study disease pathogenesis or improve meat quality. However, all of them were generated using a random integration method with variable transgene expression levels and the introduction of selectable marker genes often raise biosafety concern. To this end, we aimed to generate marker-free fat-1 transgenic pigs in a site-specific manner. The Rosa26 locus, first found in mouse embryonic stem cells, has become one of the most common sites for inserting transgenes due to its safe and ubiquitous expression. In our study, the fat-1 gene was inserted into porcine Rosa 26 (pRosa26) locus via Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. The Southern blot analysis of our knock-in pigs indicated a single copy of the fat-1 gene at the pRosa26 locus. Furthermore, this single-copy fat-1 gene supported satisfactory expression in a variety of tissues in F1 generation pigs. Importantly, the gas chromatography analysis indicated that these fat-1 knock-in pigs exhibited a significant increase in the level of n-3PUFAs, leading to an obvious decrease in the n-6PUFAs/n-3PUFAs ratio from 9.36 to 2.12 (*** P < 0.0001). Altogether, our fat-1 knock-in pigs hold great promise for improving the nutritional value of pork and serving as an animal model to investigate therapeutic effects of n-3PUFAs on various diseases. Copyright © 2018 Li et al.
Neuropathological Responses to Chronic NMDA in Rats Are Worsened by Dietary n-3 PUFA Deprivation but Are Not Ameliorated by Fish Oil Supplementation

PubMed Central

Kim, Hyung-Wook; Taha, Ameer Y.; Cheon, Yewon; Igarashi, Miki; Rapoport, Stanley I.; Rao, Jagadeesh S.

2014-01-01

Background Dietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid [18:3 n-3] but not docosahexaenoic acid [DHA, 22:6n-3]), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline. Methods Male rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose of NMDA (25 mg/kg) for 3 additional weeks. Then, brain fatty acid concentrations and various markers of excitotoxicity and fatty acid metabolism were measured. Results Compared to the diet-adequate group, brain DHA concentration was reduced, while n-6 docosapentaenoic acid (DPA, 22:5n-6) concentration was increased in the n-3 deficient group; arachidonic acid (AA, 20:4n-6) concentration was unchanged. These concentrations were unaffected by fish oil supplementation. Chronic NMDA increased brain cPLA2 activity in each of the three groups, but n-3 PUFA deprivation or fish oil did not change cPLA2 activity or protein compared with the adequate group. sPLA2 expression was unchanged in the three conditions, whereas iPLA2 expression was reduced by deprivation but not changed by supplementation. BDNF protein was reduced by NMDA in N-3 PUFA deficient rats, but protein levels of IL-1β, NGF, and GFAP did not differ between groups. Conclusions N-3 PUFA deprivation significantly worsened several pathological NMDA-induced changes produced in diet adequate rats, whereas n-3 PUFA supplementation did not affect NMDA induced changes. Supplementation may not be critical for this measured neuropathology once the diet has an adequate n-3 PUFA content. PMID:24798187
A butter diet induces higher levels of n-3 PUFA and of n-3/n-6 PUFA ratio in rat serum and hearts than a safflower oil diet.

PubMed

Hirai, K; Ozeki, Y; Nakano, T; Takezoe, R; Nakanishi, M; Asano, Y; Higuchi, H

2001-01-01

The effects of a 47-week diet of butter or safflower oil as fat in combination with casein or soy protein as protein were observed for the serum concentrations of lipids and fatty acid compositions in rat serum and heart. Serum total cholesterol (Chol) did not differ among the four experimental diet groups. In the butter groups, significantly higher low-density lipoprotein (LDL)-Chol and lower high-density lipoprotein (HDL)-Chol were observed than in the safflower oil groups (p<0.005, respectively). Higher levels of α-tocopherol were found in the butter groups than in the safflower oil groups (p<0.05) and in the casein groups than in the soy protein groups (p<0.01). In comparison with the safflower oil groups, the butter groups showed higher n-3 polyunsaturated fatty acids (PUFA) contents and lower n-6 PUFA contents in serum and the hearts (p<0.005). The ratios of n-3/n-6 PUFA in the butter groups in serum, 0.26 and 0.18, and in the hearts, 0.37 and 0.36, (butter-casein diet and butter-soy protein diet, respectively) were higher than those of the safflower oil groups of under 0.01 in serum and 0.02 and 0.03 in the hearts (safflower oil-casein diet and safflower oil-soy protein diet, respectively) (p<0.005). In the soy protein groups, higher n-3 PUFA contents in the hearts were found than those of the casein groups (p<0.05). This study suggested that the butter diet induces higher levels of n-3 PUFA and a higher n-3/n-6 PUFA ratio than the safflower oil diet in rat serum and hearts over a long feeding period.
Why and How Meet n-3 PUFA Dietary Recommendations?

PubMed Central

Molendi-Coste, Olivier; Legry, Vanessa; Leclercq, Isabelle A.

2011-01-01

Obesity and the metabolic syndrome are systemic inflammatory diseases reaching epidemic proportions. Contemporary changes in human nutrition occurred characterized by increased consumption of fat and of vegetable oils rich in n-6 polyunsaturated fatty acids (PUFAs) together with decrease in n-3 PUFA-rich foods, resulting in an n-6/n-3 ratio of 10–20/1 in Western diet for a ratio around 1/1 in the diet of our ancestors. The literature provides compelling evidence for the health benefit of n-3 PUFA consumption on inflammation and metabolic syndrome prevention and treatment. Such evidence led to the establishment of comprehensive recommendations. However, we show here that, both in collective catering proposed to children and in hospital diet, it is not straightforward to meet such recommendations. Willingness of governments to institute changes, with accountable decisions on catering, nutritional education, and food processing, is required to face our neglected responsibility in promoting balanced diet and consumption of foods rich in essential nutrients in the general population. PMID:21197079
No consequences of dietary n-3 polyunsaturated fatty acid deficiency on the severity of scopolamine-induced dry eye.

PubMed

Viau, Sabrina; Pasquis, Bruno; Maire, Marie-Annick; Fourgeux, Cynthia; Grégoire, Stéphane; Acar, Niyazi; Bretillon, Lionel; Creuzot-Garcher, Catherine P; Joffre, Corinne

2011-04-01

Epidemiological studies suggest that dietary n-3 polyunsaturated fatty acids (PUFAs) may protect against dry eye. This study aimed to evaluate whether a dietary deficiency in n-3 PUFAs may increase the severity of the pathology in a scopolamine-induced model of dry eye in the rat. Lewis rats of three consecutive generations were bred under a balanced diet or a diet deprived of n-3 PUFAs. Dry eye was experimentally induced by continuous scopolamine delivery in female animals from the third generation of both groups. After 10 days of treatment, the clinical signs of ocular dryness were evaluated in vivo using fluorescein staining. MHC II and the rat mucin rMuc5AC were immunostained on ocular sphere cryosections. The transcript levels of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were quantified in the exorbital lacrimal glands (LG) and in the conjunctiva using reverse transcription followed by polymerase chain reaction. Lipids were extracted from the exorbital LG for fatty acid analysis of the phospholipids using gas chromatography. When compared to control animals, the scopolamine treatment induced an increase in the cornea fluorescein staining score (from 0.5 ± 0.0 to 2.5 ± 1.0 arbitrary units (AU) for the balanced diet and from 1.2 ± 0.8 to 2.6 ± 0.5 AU for the n-3 PUFA-deficient diet); a decrease in rMuc5AC immunostaining in the conjunctival epithelium (-34% for the balanced diet and -23% for the n-3 PUFA-deficient diet); an increase in the LG transcript levels of TNF-α for the balanced diet and of TNF-α and IFN-γ for the deficient diet; an increase in the conjunctival transcript levels of IL-1β and IL-6 for the deficient diet; an increase in arachidonic acid (AA) and in the ∆5-desaturase index (ratio of AA to dihomo-gamma-linolenic acid) in the exorbital LG for both diets. When compared to the balanced diet, the n-3 PUFA-deficient diet induced an increase in the LG transcript levels
Are n-3 PUFA dietary recommendations met in in-hospital and school catering?

PubMed

Molendi-Coste, O; Legry, V; Leclercq, I A

2011-06-01

Literature provides compelling evidence for the health benefits of n-3 polyunsaturated fatty acids (PUFA) consumption and low n-6/n-3 ratio, in particular, on inflammation and metabolic syndrome prevention and treatment. Consequently, recommendations were established for adequate n-3 PUFA supplies in the general population. The aim of our study was to evaluate the fatty acid (FA) profile in collective catering in relation to those recommendations. We obtained composition of lunches provided by the Township of Lille (France) to children and adults, and of "standard", "low-fat" and "for diabetic" menus from the catering service of St Luc university hospital (Brussels, Belgium). The average proportions of fish, meat, oils, and dairy were used to estimate total, saturated, monounsaturated and polyunsaturated (n-6 and n-3) FA contents. We used official tables of foodstuffs composition provided by the French Agency for Food Safety, the project "Nutritional Composition of Aquatic Products", the French Institute for Nutrition, and the USDA National Nutrient Database for Standard Reference. French guidelines were taken as reference for daily recommended intakes. n-3 PUFA content in lunches provided by municipal catering and in in-hospital menus were slightly below recommended intakes. In the latter, n-3 PUFA enriched margarine contributed for 50% to daily intakes. Despite, the n-6/n-3 ratio was too high, especially in municipal catering (around 20), related to excessive n-6 PUFA supply. Our results highlight that meeting n-3 PUFA nutritional recommendation remains challenging for collective catering. A detailed analysis of provided menus represents a powerful tool to increase awareness and foster improvement in practice.
ELOVL4 protein preferentially elongates 20:5n3 to very long chain PUFAs over 20:4n6 and 22:6n3[S

PubMed Central

Yu, Man; Benham, Aaron; Logan, Sreemathi; Brush, R. Steven; Mandal, Md Nawajes A.; Anderson, Robert E.; Agbaga, Martin-Paul

2012-01-01

We hypothesized that reduction/loss of very long chain PUFAs (VLC-PUFAs) due to mutations in the ELOngase of very long chain fatty acid-4 (ELOVL4) protein contributes to retinal degeneration in autosomal dominant Stargardt-like macular dystrophy (STGD3) and age-related macular degeneration; hence, increasing VLC-PUFA in the retina of these patients could provide some therapeutic benefits. Thus, we tested the efficiency of elongation of C20-C22 PUFA by the ELOVL4 protein to determine which substrates are the best precursors for biosynthesis of VLC-PUFA. The ELOVL4 protein was expressed in pheochromocytoma cells, while green fluorescent protein-expressing and nontransduced cells served as controls. The cells were treated with 20:5n3, 22:6n3, and 20:4n6, either individually or in equal combinations. Both transduced and control cells internalized and elongated the supplemented FAs to C22-C26 precursors. Only ELOVL4-expressing cells synthesized C28-C38 VLC-PUFA from these precursors. In general, 20:5n3 was more efficiently elongated to VLC-PUFA in the ELOVL4-expressing cells, regardless of whether it was in combination with 22:6n3 or with 20:4n6. In each FA treatment group, C34 and C36 VLC-PUFAs were the predominant VLC-PUFAs in the ELOVL4-expressing cells. In summary, 20:5n3, followed by 20:4n6, seems to be the best precursor for boosting the synthesis of VLC-PUFA by ELOVL4 protein. PMID:22158834
Impact of diesel exhaust exposure on the liver of mice fed on omega-3 polyunsaturated fatty acids-deficient diet.

PubMed

Umezawa, Masakazu; Nakamura, Masayuki; El-Ghoneimy, Ashraf A; Onoda, Atsuto; Shaheen, Hazem M; Hori, Hiroshi; Shinkai, Yusuke; El-Sayed, Yasser S; El-Far, Ali H; Takeda, Ken

2018-01-01

Exposure to diesel exhaust (DE) exacerbates non-alcoholic fatty liver disease, and may systemically affect lipid metabolism. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have anti-inflammatory activity and suppresses hepatic triacylglycerol accumulation, but many daily diets are deficient in this nutrient. Therefore, the effect of DE exposure in mice fed n-3 PUFA-deficient diet was investigated. Mice were fed control chow or n-3 PUFA-deficient diet for 4 weeks, then exposed to clean air or DE by inhalation for further 4 weeks. Liver histology, plasma parameters, and expression of fatty acid synthesis-related genes were evaluated. N-3 PUFA-deficient diet increased hepatic lipid droplets accumulation and expression of genes promoting fatty acid synthesis: Acaca, Acacb, and Scd1. DE further increased the plasma leptin and the expression of fatty acid synthesis-related genes: Acacb, Fasn, and Scd1. N-3 PUFA-deficient diet and DE exposure potentially enhanced hepatic fatty acid synthesis and subsequently accumulation of lipid droplets. The combination of low-dose DE exposure and intake of n-3 PUFA-deficient diet may be an additional risk factor for the incidence of non-alcoholic fatty liver disease. The present study suggests an important mechanism for preventing toxicity of DE on the liver through the incorporation of n-3 PUFAs in the diet. Copyright © 2017 Elsevier Ltd. All rights reserved.
Dietary n-3 PUFAs augment caspase 8 activation in Staphylococcal aureus enterotoxin B stimulated T-cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gill, R.

Epidemiological studies have linked consumption of n-3 PUFAs with a variety of beneficial health benefits, particularly with respect to putative anti-inflammatory effects. Unfortunately, many of these results remain somewhat controversial because in most instances there has not been a linkage to specific molecular mechanisms. For instance, dietary exposure to low levels of mercury has been shown to be damaging to neural development, but concomitant ingestion of n-3 PUFAs as occurs during consumption of fish, has been shown to counteract the detrimental effects. As the mechanisms mediating the neurotoxicity of environmental mercury are not fully delineated, it is difficult to conceptualizemore » a testable molecular mechanism explaining how n-3 PUFAs negate its neurotoxic effects. However, environmental exposure to mercury also has been linked to increased autoimmunity. By way of a molecular understanding of this immuno-toxic association, disruption of CD95 signaling is well established as a triggering factor for autoimmunity, and we have previously shown that environmentally relevant in vitro and dietary exposures to mercury interfere with CD95 signaling. In particular we have shown that activation of caspase 8, as well as downstream activation of caspase 3, in response to CD95 agonist stimulation is depressed by mercury. More recently we have shown in vitro that the n-3 PUFA docosahexaenoic acid counteracts the negative effect of mercury on CD95 signaling by restoring caspase activity. We hypothesized that concomitant ingestion of n-3 PUFAs with mercury might be protective from the immuno-toxic effects of mercury, as it is with mercury's neuro-toxic effects, and in the case of immuno-toxicity this would be related to restoration of CD95 signal strength. We now show that dietary ingestion of n-3 PUFAs generally promotes CD95 signaling by upregulating caspase 8 activation. Apart from accounting for the ability of n-3 PUFAs to specifically counteract autoimmune
Effects of n-3 PUFAs on Intestinal Mucosa Innate Immunity and Intestinal Microbiota in Mice after Hemorrhagic Shock Resuscitation.

PubMed

Tian, Feng; Gao, Xuejin; Zhang, Li; Wang, Xinying; Wan, Xiao; Jiang, Tingting; Wu, Chao; Bi, Jingcheng; Lei, Qiucheng

2016-09-29

n -3 polyunsaturated fatty acids (PUFAs) can improve the function of the intestinal barrier after damage from ischemia-reperfusion or hemorrhagic shock resuscitation (HSR). However, the effects of n -3 PUFAs on intestinal microbiota and the innate immunity of the intestinal mucosa after HSR remain unclear. In the present study, 40 C57BL/6J mice were randomly assigned to five groups: control, sham, HSR, HSR + n -3 PUFAs and HSR + n -6 PUFAs. Mice were sacrificed 12 h after HSR. Liver, spleen, mesenteric lymph nodes and terminal ileal tissues were collected. Intestinal mucosae were scraped aseptically. Compared with the HSR group, the number of goblet cells increased, expression of mucin 2 was restored and disturbed intestinal microbiota were partly stabilized in the PUFA-administered groups, indicating that both n -3 and n -6 PUFAs reduced overproliferation of Gammaproteobacteria while promoting the growth of Bacteroidetes. Notably, n -3 PUFAs had an advantage over n -6 PUFAs in improving ileal tissue levels of lysozyme after HSR. Thus, PUFAs, especially n -3 PUFAs, partly improved the innate immunity of intestinal mucosa in mice after HSR. These findings suggest a clinical rationale for providing n -3 PUFAs to patients recovering from ischemia-reperfusion.
Low n-6/n-3 PUFA Ratio Improves Lipid Metabolism, Inflammation, Oxidative Stress and Endothelial Function in Rats Using Plant Oils as n-3 Fatty Acid Source.

PubMed

Yang, Li Gang; Song, Zhi Xiu; Yin, Hong; Wang, Yan Yan; Shu, Guo Fang; Lu, Hui Xia; Wang, Shao Kang; Sun, Gui Ju

2016-01-01

Lipid metabolism, inflammation, oxidative stress and endothelial function play important roles in the pathogenesis of cardiovascular disease (CVD), which may be affected by an imbalance in the n-6/n-3 polyunsaturated fatty acid (PUFA) ratio. This study aimed to investigate the effects of the n-6/n-3 PUFA ratio on these cardiovascular risk factors in rats fed a high-fat diet using plant oils as the main n-3 PUFA source. The 1:1 and 5:1 ratio groups had significantly decreased serum levels of total cholesterol, low-density lipoprotein cholesterol, and proinflammatory cytokines compared with the 20:1 group (p < 0.05). Additionally, the 20:1 group had significantly increased serum levels of E-Selectin, von Willebrand factor (vWF), and numerous markers of oxidative stress compared with the other groups (p < 0.05). The 1:1 group had a significantly decreased lipid peroxide level compared with the other groups (p < 0.05). Serum levels of malondialdehyde, reactive oxygen species and vWF tended to increase with n-6/n-3 PUFA ratios increasing from 5:1 to 20:1. We demonstrated that low n-6/n-3 PUFA ratio (1:1 and 5:1) had a beneficial effect on cardiovascular risk factors by enhancing favorable lipid profiles, having anti-inflammatory and anti-oxidative stress effects, and improving endothelial function. A high n-6/n-3 PUFA ratio (20:1) had adverse effects. Our results indicated that low n-6/n-3 PUFA ratios exerted beneficial cardiovascular effects, suggesting that plant oils could be used as a source of n-3 fatty acids to prevent CVD. They also suggested that we should be aware of possible adverse effects from excessive n-3 PUFA.
A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans.

PubMed

Wood, K E; Lau, A; Mantzioris, E; Gibson, R A; Ramsden, C E; Muhlhausler, B S

2014-04-01

This study aimed to determine the effect of reducing the dietary linoleic acid (LA) intake from ~5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks. Nutrient intakes were estimated from diet diaries and blood samples were collected for assessment of fatty acid composition in plasma and erythrocyte phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA intervention (P<0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were significantly reduced after the low LA diet phase (P<0.001). The n-3 LCPUFA content of plasma phospholipids was significantly increased after the low LA diet compared to baseline (6.22% vs. 5.53%, P<0.001). These data demonstrate that reducing LA intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake. Copyright © 2014 Elsevier Ltd. All rights reserved.
Variation Quality and Kinetic Parameter of Commercial n-3 PUFA-Rich Oil during Oxidation via Rancimat

PubMed Central

Yang, Kai-Min; Chiang, Po-Yuan

2017-01-01

Different biological sources of n-3 polyunsaturated fatty acids (n-3 PUFA) in mainstream commercial products include algae and fish. Lipid oxidation in n-3 PUFA-rich oil is the most important cause of its deterioration. We investigated the kinetic parameters of n-3 PUFA-rich oil during oxidation via Rancimat (at a temperature range of 70~100 °C). This was done on the basis of the Arrhenius equation, which indicates that the activation energies (Ea) for oxidative stability are 82.84–96.98 KJ/mol. The chemical substrates of different oxidative levels resulting from oxidation via Rancimat at 80 °C were evaluated. At the initiation of oxidation, the tocopherols in the oil degraded very quickly, resulting in diminished protection against further oxidation. Then, the degradation of the fatty acids with n-3 PUFA-rich oil was evident because of decreased levels of PUFA along with increased levels of saturated fatty acids (SFA). The quality deterioration from n-3 PUFA-rich oil at the various oxidative levels was analyzed chemometrically. The anisidine value (p-AV, r: 0.92) and total oxidation value (TOTOX, r: 0.91) exhibited a good linear relationship in a principal component analysis (PCA), while oxidative change and a significant quality change to the induction period (IP) were detected through an agglomerative hierarchical cluster (AHC) analysis. PMID:28350348
Variation Quality and Kinetic Parameter of Commercial n-3 PUFA-Rich Oil during Oxidation via Rancimat.

PubMed

Yang, Kai-Min; Chiang, Po-Yuan

2017-03-28

Different biological sources of n -3 polyunsaturated fatty acids ( n -3 PUFA) in mainstream commercial products include algae and fish. Lipid oxidation in n -3 PUFA-rich oil is the most important cause of its deterioration. We investigated the kinetic parameters of n -3 PUFA-rich oil during oxidation via Rancimat (at a temperature range of 70~100 °C). This was done on the basis of the Arrhenius equation, which indicates that the activation energies ( E a) for oxidative stability are 82.84-96.98 KJ/mol. The chemical substrates of different oxidative levels resulting from oxidation via Rancimat at 80 °C were evaluated. At the initiation of oxidation, the tocopherols in the oil degraded very quickly, resulting in diminished protection against further oxidation. Then, the degradation of the fatty acids with n -3 PUFA-rich oil was evident because of decreased levels of PUFA along with increased levels of saturated fatty acids (SFA). The quality deterioration from n -3 PUFA-rich oil at the various oxidative levels was analyzed chemometrically. The anisidine value (p-AV, r: 0.92) and total oxidation value (TOTOX, r: 0.91) exhibited a good linear relationship in a principal component analysis (PCA), while oxidative change and a significant quality change to the induction period (IP) were detected through an agglomerative hierarchical cluster (AHC) analysis.
Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats

PubMed Central

Mehus, Aaron A.; Picklo, Sr, Matthew J.

2017-01-01

Metallothioneins (MTs) perform important regulatory and cytoprotective functions in tissues including the brain. While it is known that energy restriction (ER) and dietary n-3 polyunsaturated fatty acid (PUFA) deficiency impact postnatal brain growth and development, little data exist regarding the impact of undernutrition upon MT expression in growing animals. We tested the hypothesis that ER with and without dietary n-3 PUFA deficiency reduces MT expression in juvenile rats. ER rats were individually pair-fed at 75% of the ad libitum (AL) intake of control rats provided diets consisting of either soybean oil (SO) that is α-linolenic acid (ALA; 18:3n-3) sufficient or corn oil (CO; ALA-deficient). Fatty acids (FA) and metal concentrations of liver and brain regions were analyzed. Tissue expression of MTs (Mt1-3) and modulators of MT expression including glucocorticoid receptors (Nr3c1 and Nr3c2) and several mediators of thyroid hormone regulation (Dio1-3, Mct8, Oatp1c1, Thra, and Thrb) were measured. Plasma corticosterone and triiodothyronine levels were also evaluated. ER, but not metal deficiency, reduced Mt2 expression in the cerebellum (50%) and cerebral cortex (23%). In liver, a reduction in dietary n-3 PUFA reduced Mt1, Mt2, Nr3c1, Mct8, and Thrb. ER elevated Nr3c1, Dio1, and Thrb and reduced Thra in the liver. Given MT’s role in cellular protection, further studies are needed to evaluate whether ER or n-3 PUFA deficiency may leave the juvenile brain and/or liver more susceptible to endogenous or environmental stressors. PMID:29048374
Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats.

PubMed

Mehus, Aaron A; Picklo, Matthew J

2017-10-19

Metallothioneins (MTs) perform important regulatory and cytoprotective functions in tissues including the brain. While it is known that energy restriction (ER) and dietary n -3 polyunsaturated fatty acid (PUFA) deficiency impact postnatal brain growth and development, little data exist regarding the impact of undernutrition upon MT expression in growing animals. We tested the hypothesis that ER with and without dietary n -3 PUFA deficiency reduces MT expression in juvenile rats. ER rats were individually pair-fed at 75% of the ad libitum (AL) intake of control rats provided diets consisting of either soybean oil (SO) that is α-linolenic acid (ALA; 18:3 n -3) sufficient or corn oil (CO; ALA-deficient). Fatty acids (FA) and metal concentrations of liver and brain regions were analyzed. Tissue expression of MTs ( Mt1-3 ) and modulators of MT expression including glucocorticoid receptors ( Nr3c1 and Nr3c2 ) and several mediators of thyroid hormone regulation ( Dio1-3 , Mct8 , Oatp1c1 , Thra , and Thrb ) were measured. Plasma corticosterone and triiodothyronine levels were also evaluated. ER, but not metal deficiency, reduced Mt2 expression in the cerebellum (50%) and cerebral cortex (23%). In liver, a reduction in dietary n -3 PUFA reduced Mt1 , Mt2 , Nr3c1 , Mct8 , and Thrb . ER elevated Nr3c1 , Dio1 , and Thrb and reduced Thra in the liver. Given MT's role in cellular protection, further studies are needed to evaluate whether ER or n -3 PUFA deficiency may leave the juvenile brain and/or liver more susceptible to endogenous or environmental stressors.
Randomized placebo-controlled intervention with n-3 LC-PUFA-supplemented yoghurt: effects on circulating eicosanoids and cardiovascular risk factors.

PubMed

Dawczynski, Christine; Massey, Karen A; Ness, Christina; Kiehntopf, Michael; Stepanow, Stefanie; Platzer, Matthias; Grün, Michael; Nicolaou, Anna; Jahreis, Gerhard

2013-10-01

The study examined the value of n-3 LC-PUFA-enriched yogurt as means of improving cardiovascular health. Fifty three mildly hypertriacylglycerolemic subjects (TAG ≥ 1.7 mmol/L) participated in a randomized, placebo-controlled, double-blind, parallel designed study. The subjects consumed 1) control yoghurt; 2) yoghurt enriched with 0.8 g n-3 LC-PUFA/d; or 3) yoghurt enriched with 3 g n-3 LC-PUFA/d for a period of 10 wks. Blood samples were taken at the beginning and the end of the study period. Following daily intake of 3 g n-3 LC-PUFA for 10 weeks, n-3 LC-PUFA levels increased significantly in plasma and red blood cells (RBC) with concomitant increase in the EPA-derived mediators (PGE₃, 12-, 15-, 18-HEPE) in plasma whilst cardiovascular risk factors such as HDL, TAG, AA/EPA ratio, and n-3 index were improved (P < 0.05); the decrease of TAG and increase in HDL were associated with the CD36 genotype. The observed increase of n-3 LC-PUFA in RBC and plasma lipids due to intake of n-3 LC-PUFA enriched yoghurt resulted in a reduction of cardiovascular risk factors and inflammatory mediators showing that daily consumption of n-3 PUFA enriched yoghurt can be an effective way of supplementing the daily diet and improving cardiovascular health. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.
Three-way assessment of long-chain n-3 PUFA nutrition: by questionnaire and matched blood and skin samples.

PubMed

Wallingford, Sarah C; Pilkington, Suzanne M; Massey, Karen A; Al-Aasswad, Naser M I; Ibiebele, Torukiri I; Celia Hughes, Maria; Bennett, Susan; Nicolaou, Anna; Rhodes, Lesley E; Green, Adèle C

2013-02-28

The long-chain n-3 PUFA, EPA, is believed to be important for skin health, including roles in the modulation of inflammation and protection from photodamage. FFQ and blood levels are used as non-invasive proxies for assessing skin PUFA levels, but studies examining how well these proxies reflect target organ content are lacking. In seventy-eight healthy women (mean age 42·8, range 21-60 years) residing in Greater Manchester, we performed a quantitative analysis of long-chain n-3 PUFA nutrition estimated from a self-reported FFQ (n 75) and correlated this with n-3 PUFA concentrations in erythrocytes (n 72) and dermis (n 39). Linear associations between the three n-3 PUFA measurements were assessed by Spearman correlation coefficients and agreement between these measurements was estimated. Average total dietary content of the principal long-chain n-3 PUFA EPA and DHA was 171 (SD 168) and 236 (SD 248) mg/d, respectively. EPA showed significant correlations between FFQ assessments and both erythrocyte (r 0·57, P< 0·0001) and dermal (r 0·33, P= 0·05) levels, as well as between erythrocytes and dermis (r 0·45, P= 0·008). FFQ intake of DHA and the sum of n-3 PUFA also correlated well with erythrocyte concentrations (r 0·50, P< 0·0001; r 0·27, P= 0·03). Agreement between ranked thirds of dietary intake, blood and dermis approached 50% for EPA and DHA, though gross misclassification was lower for EPA. Thus, FFQ estimates and circulating levels of the dietary long-chain n-3 PUFA, EPA, may be utilised as well-correlated measures of its dermal bioavailability.

The association of serum long-chain n-3 PUFA and hair mercury with exercise cardiac power in men.

PubMed

Tajik, Behnam; Kurl, Sudhir; Tuomainen, Tomi-Pekka; Virtanen, Jyrki K

2016-08-01

Long-chain n-3 PUFA from fish and exercise capacity are associated with CVD risk. Fish, especially large and old predatory fish, may contain Hg, which may attenuate the inverse association of long-chain n-3 PUFA with CVD. However, the associations of long-chain n-3 PUFA or Hg exposure with exercise capacity are not well known. We aimed to evaluate the associations of serum long-chain n-3 PUFA EPA, docosapentaenoic acid (DPA) and DHA and hair Hg with exercise cardiac power (ECP, a ratio of VO2max:maximal systolic blood pressure (SBP) during an exercise test), a measure for exercise capacity. For this, data from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study were analysed cross-sectionally in order to determine the associations between serum long-chain n-3 PUFA, hair Hg and ECP in 1672 men without CVD, aged 42-60 years. After multivariate adjustments, serum total long-chain n-3 PUFA concentration was associated with higher ECP and VO2max (P trend across quartiles=0·04 and P trend=0·02, respectively), but not with maximal SBP (P trend=0·69). Associations were generally similar when EPA, DPA and DHA were evaluated individually. Hair Hg was not associated with ECP, VO2max or maximal SBP. However, the associations of total long-chain n-3 PUFA (P interaction=0·03) and EPA (P interaction=0·02) with higher VO2max were stronger among men with lower hair Hg. Higher serum long-chain n-3 PUFA concentration, mainly a marker for fish consumption in this study population, was associated with higher ECP and VO2max in middle-aged men from eastern Finland.
Sex-dependent association between erythrocyte n-3 PUFA and type 2 diabetes in older overweight people.

PubMed

Abbott, Kylie A; Veysey, Martin; Lucock, Mark; Niblett, Suzanne; King, Katrina; Burrows, Tracy; Garg, Manohar L

2016-04-01

The association between n-3 PUFA intake and type 2 diabetes (T2D) is unclear, and studies relating objective biomarkers of n-3 PUFA consumption to diabetic status remain limited. The aim of this study was to determine whether erythrocyte n-3 PUFA levels (n-3 index; n-3I) are associated with T2D in a cohort of older adults (n 608). To achieve this, the n-3I (erythrocyte %EPA+%DHA) was determined by GC and associated with fasting blood glucose; HbA1c; and plasma insulin. Insulin resistance (IR) was assessed using the homeostatic model assessment of insulin resistance (HOMA--IR). OR for T2D were calculated for each quartile of n-3I. In all, eighty-two type 2 diabetic (46·3 % female; 76·7 (sd 5·9) years) and 466 non-diabetic (57·9 % female; 77·8 (sd 7·1) years) individuals were included in the analysis. In overweight/obese (BMI≥27 kg/m2), the prevalence of T2D decreased across ascending n-3I quartiles: 1·0 (reference), 0·82 (95 % CI 0·31, 2·18), 0·56 (95 % CI 0·21, 1·52) and 0·22 (95 % CI 0·06, 0·82) (P trend=0·015). A similar but non-significant trend was seen in overweight men. After adjusting for BMI, no associations were found between n-3I and fasting blood glucose, HbA1c, insulin or HOMA-IR. In conclusion, higher erythrocyte n-3 PUFA status may be protective against the development of T2D in overweight women. Further research is warranted to determine whether dietary interventions that improve n-3 PUFA status can improve measures of IR, and to further elucidate sex-dependent differences.
Effects of supplementation with fish oil and n-3 PUFAs enriched egg yolk phospholipids on anhedonic-like response and body weight in the rat chronic mild stress model of depression.

PubMed

Rutkowska, M; Trocha, M; Szandruk, M; Słupski, W; Rymaszewska, J

2013-08-01

Polyunsaturated fatty acids play an important role in the human organism. They guarantee a normal function of nervous cells, influence neurotransmission, and build some elements of cellular membranes. Several reports indicate an association between a deficiency of polyunsaturated fatty acids and depression. The aim of this study was to examine the effects of diet supplemented with fish oil, which is rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) and n-3 PUFAs enriched phospholipids ("super lecithin") obtained from designed eggs on anhedonic-like response and body weight in the rat chronic mild stress (CMS) model of depression. The results showed that neither fish oil nor n-3 PUFAs enriched egg yolk phospholipids supplementation reversed disturbances caused by CMS, such as anhedonic-like state or reduction of body weight gain.
The n-3 long-chain PUFAs modulate the impact of the GCKR Pro446Leu polymorphism on triglycerides in adolescents.

PubMed

Rousseaux, Julien; Duhamel, Alain; Dumont, Julie; Dallongeville, Jean; Molnar, Denes; Widhalm, Kurt; Manios, Yannis; Sjöström, Michael; Kafatos, Anthony; Breidenassel, Christina; Gonzales-Gross, Marcela; Cuenca-Garcia, Magdalena; Censi, Laura; Ascensión, Marcos; De Henauw, Stefaan; Moreno, Luis A; Meirhaeghe, Aline; Gottrand, Frédéric

2015-09-01

Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.
Influence of dietary n-3 LC-PUFA on growth, nutritional composition and immune function in marine fish Sebastiscus marmoratus

NASA Astrophysics Data System (ADS)

Peng, Shiming; Yue, Yanfeng; Gao, Quanxin; Shi, Zhaohong; Yin, Fei; Wang, Jiangang

2014-09-01

A 60-day feeding experiment was conducted to investigate the influence of dietary omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) on growth, nutritional composition and immune function of marine fish Sebastiscus marmoratus. Five diets containing 3.6, 10.2, 18.2, 26.5, or 37.0 g/kg n-3 LC-PUFA were prepared. The results reveal significant influences of dietary n-3 LC-PUFA on the final weight, weight gain, specific growth rate, feed conversion ratio, and condition factor. As dietary n-3 LCPUFA increased, weight gain and specific growth rate increased and were significantly higher in groups fed 18.2, 26.5 and 37.0 g/kg than in groups fed 3.6 and 10.2 g/kg ( P<0.05); there was no significant difference between groups fed 18.2, 26.5, or 37.0 g/kg ( P>0.05). With increasing dietary n-3 LC-PUFA, eicosapentaenoic acid and docosahexenoic acid content in muscle and liver increased significantly, immunoglobulin class M content gradually increased from 9.1 to 14.8 μg/L, and lysozyme activity content increased from 1 355 to 2 268 U/mL. Broken line model analysis according to weight gain indicated that a dietary n-3 LC-PUFA level of 18.2 g/kg is essential for normal growth at a fat level of 125 g/kg. Therefore, appropriate dietary n-3 LC-PUFA not only promote growth and improve the n-3 LC-PUFA content, but also enhance immune function in S. marmoratus.
Effects of Dietary n-6:n-3 PUFA Ratios on Lipid Levels and Fatty Acid Profile of Cherry Valley Ducks at 15-42 Days of Age.

PubMed

Li, Mengmeng; Zhai, Shuangshuang; Xie, Qiang; Tian, Lu; Li, Xiaocun; Zhang, Jiaming; Ye, Hui; Zhu, Yongwen; Yang, Lin; Wang, Wence

2017-11-22

The objective of this study was to investigate the effects of dietary n-6:n-3 PUFA ratio on growth performance, serum and tissue lipid levels, fatty acid profile, and hepatic expression of fatty acid synthesis genes in ducks. A total of 3168 15-day old ducks were fed different n-6:n-3 PUFA ratios: 13:1 (control), 10:1, 8:1, 6:1, 4:1, and 2:1. The feeding trial lasted 4 weeks. Our results revealed that dietary n-6:n-3 PUFA ratios had no effects on growth performance. The 2:1 group had the highest serum triglyceride levels. Serum total cholesterol and HDL levels were higher in the 13:1 and 8:1 groups than in the 6:1 and 2:1 groups. The concentration of C18:3n-3 in serum and tissues (liver and muscle) increased with decreasing dietary n-6:n-3 PUFA ratios. The hepatic expression of FADS2, ELOVL5, FADS1, and ELOVL2 increased on a quadratic function with decreasing dietary n-6:n-3 PUFA ratios. These results demonstrate that lower dietary n-6:n-3 PUFA ratios had strong effects on the fatty acid profile of edible parts and the deposition of n-3 PUFAs in adipose tissue of ducks.
The n-3 long-chain PUFAs modulate the impact of the GCKR Pro446Leu polymorphism on triglycerides in adolescents[S

PubMed Central

Rousseaux, Julien; Duhamel, Alain; Dumont, Julie; Dallongeville, Jean; Molnar, Denes; Widhalm, Kurt; Manios, Yannis; Sjöström, Michael; Kafatos, Anthony; Breidenassel, Christina; Gonzales-Gross, Marcela; Cuenca-Garcia, Magdalena; Censi, Laura; Ascensión, Marcos; De Henauw, Stefaan; Moreno, Luis A.; Meirhaeghe, Aline; Gottrand, Frédéric

2015-01-01

Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings. PMID:26136510
Membrane raft organization is more sensitive to disruption by (n-3) PUFA than nonraft organization in EL4 and B cells.

PubMed

Rockett, Benjamin Drew; Franklin, Andrew; Harris, Mitchel; Teague, Heather; Rockett, Alexis; Shaikh, Saame Raza

2011-06-01

Model membrane and cellular detergent extraction studies show (n-3) PUFA predominately incorporate into nonrafts; thus, we hypothesized (n-3) PUFA could disrupt nonraft organization. The first objective of this study was to determine whether (n-3) PUFA disrupted nonrafts of EL4 cells, an extension of our previous work in which we discovered an (n-3) PUFA diminished raft clustering. EPA or DHA treatment of EL4 cells increased plasma membrane accumulation of the nonraft probe 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate by ~50-70% relative to a BSA control. Förster resonance energy transfer imaging showed EPA and DHA also disrupted EL4 nanometer scale nonraft organization by increasing the distance between nonraft molecules by ~25% compared with BSA. However, changes in nonrafts were due to an increase in cell size; under conditions where EPA or DHA did not increase cell size, nonraft organization was unaffected. We next translated findings on EL4 cells by testing if (n-3) PUFA administered to mice disrupted nonrafts and rafts. Imaging of B cells isolated from mice fed low- or high-fat (HF) (n-3) PUFA diets showed no change in nonraft organization compared with a control diet (CD). However, confocal microscopy revealed the HF (n-3) PUFA diet disrupted lipid raft clustering and size by ~40% relative to CD. Taken together, our data from 2 different model systems suggest (n-3) PUFA have limited effects on nonrafts. The ex vivo data, which confirm previous studies with EL4 cells, provide evidence that (n-3) PUFA consumed through the diet disrupt B cell lipid raft clustering.
Characterization of Volatile Compounds with HS-SPME from Oxidized n-3 PUFA Rich Oils via Rancimat Tests.

PubMed

Yang, Kai-Min; Cheng, Ming-Ching; Chen, Chih-Wei; Tseng, Chin-Yin; Lin, Li-Yun; Chiang, Po-Yuan

2017-02-01

Algae oil and fish oil are n-3 PUFA mainstream commercial products. The various sources for the stability of n-3 PUFA oxidation are influenced by the fatty acid composition, extraction and refined processing. In this study, the oil stability index (OSI) occurs within 2.3 to 7.6 hours with three different n-3 PUFA rich oil. To set the OSI in the Rancimat test as the oil stability limit and observed various degrees of oxidation (0, 25, 50, 75, 100 and 125%). The volatile oxidation compounds were analyzed via headspace-solid phase microextraction (HS-SPME) and GC/MS. We detected 51 volatile compound variations during the oxidation, which were composed of aldehydes, hydrocarbons, cyclic compounds, alcohols, benzene compounds, ketones, furans, ester and pyrrolidine. The off-flavor characteristics can be strongly influenced by the synergy effects of volatile oxidation compounds. Chemometric analysis (PCA and AHC) was applied to identify the sensitive oxidation marker compounds, which included a (E,E)-2,4-heptadienal appropriate marker, via lipid oxidation in the n-3 PUFA rich oil.
n-3 PUFA esterified to glycerol or as ethyl esters reduce non-fasting plasma triacylglycerol in subjects with hypertriglyceridemia: a randomized trial.

PubMed

Hedengran, Anne; Szecsi, Pal B; Dyerberg, Jørn; Harris, William S; Stender, Steen

2015-02-01

To date, treatment of hypertriglyceridemia with long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non-fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective of this study was to investigate the effect of long-chain n-3 PUFA on non-fasting triacylglycerol levels and to compare the effects of n-3 PUFA formulated as acylglycerol (AG-PUFA) or ethyl esters (EE-PUFA). The study was a double-blinded randomized placebo-controlled interventional trial, and included 120 subjects with non-fasting plasma triacylglycerol levels of 1.7-5.65 mmol/L (150-500 mg/dL). The participants received approximately 3 g/day of AG-PUFA, EE-PUFA, or placebo for a period of eight weeks. The levels of non-fasting plasma triacylglycerols decreased 28% in the AG-PUFA group and 22% in the EE-PUFA group (P < 0.001 vs. placebo), with no significant difference between the two groups. The triacylglycerol lowering effect was evident after four weeks, and was inversely correlated with the omega-3 index (EPA + DHA content in erythrocyte membranes). The omega-3 index increased 63.2% in the AG-PUFA group and 58.5% in the EE-PUFA group (P < 0.001). Overall, the heart rate in the AG-PUFA group decreased by three beats per minute (P = 0.045). High-density lipoprotein (HDL) cholesterol increased in the AG-PUFA group (P < 0.001). Neither total nor non-HDL cholesterol changed in any group. Lipoprotein-associated phospholipase A2 (LpPLA2) decreased in the EE-PUFA group (P = 0.001). No serious adverse events were observed. Supplementation with long-chain n-3 PUFA lowered non-fasting triacylglycerol levels, suggestive of a reduction in cardiovascular risk. Regardless of the different effects on heart rate, HDL, and LpPLA2 that were observed, compared to placebo, AG-PUFA, and EE-PUFA are equally effective in reducing non-fasting triacylglycerol levels.
Fish, a Mediterranean source of n-3 PUFA: benefits do not justify limiting consumption.

PubMed

Gil, Angel; Gil, Fernando

2015-04-01

Fish is an important source of energy, high-quality proteins, fat, vitamins and minerals. Within lipids, n-3 long-chain PUFA (n-3 LC PUFA), mainly EPA and DHA, play an important role in health promotion and disease prevention. In contrast to the potential health benefits of dietary fish intake, certain chemical pollutants, namely heavy metals and some organic compounds, contained in seafood have emerged as an issue of concern, particularly for frequent fish consumers and sensitive groups of populations. The present review summarises the health benefits and risks of fish consumption. n-3 LC-PUFA are key compounds of cell membranes and play an important role in human health from conception through every stage of human development, maturation and ageing. DHA has a major role in the development of brain and retina during fetal development and the first 2 years of life and positively influences neurodevelopment, mainly visual acuity and cognitive functions. n-3 LC-PUFA are also effective in preventing cardiovascular events (mainly stroke and acute myocardial infarction) especially in persons with high cardiovascular risk. By contrast, there is convincing evidence of adverse neurological/neurodevelopmental outcomes in infants and young children associated with methylmercury exposure during fetal development due to maternal fish consumption during pregnancy. Dioxins and polychlorinated biphenyls present in contaminated fish may also develop a risk for both infants and adults. However, for major health outcomes among adults, the vast majority of epidemiological studies have proven that the benefits of fish intake exceed the potential risks with the exception of a few selected species in sensitive populations.
Membrane Raft Organization Is More Sensitive to Disruption by (n-3) PUFA Than Nonraft Organization in EL4 and B Cells123

PubMed Central

Rockett, Benjamin Drew; Franklin, Andrew; Harris, Mitchel; Teague, Heather; Rockett, Alexis; Shaikh, Saame Raza

2011-01-01

Model membrane and cellular detergent extraction studies show (n-3) PUFA predominately incorporate into nonrafts; thus, we hypothesized (n-3) PUFA could disrupt nonraft organization. The first objective of this study was to determine whether (n-3) PUFA disrupted nonrafts of EL4 cells, an extension of our previous work in which we discovered an (n-3) PUFA diminished raft clustering. EPA or DHA treatment of EL4 cells increased plasma membrane accumulation of the nonraft probe 1,1′-dilinoleyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate by ~50–70% relative to a BSA control. Förster resonance energy transfer imaging showed EPA and DHA also disrupted EL4 nanometer scale nonraft organization by increasing the distance between nonraft molecules by ~25% compared with BSA. However, changes in nonrafts were due to an increase in cell size; under conditions where EPA or DHA did not increase cell size, nonraft organization was unaffected. We next translated findings on EL4 cells by testing if (n-3) PUFA administered to mice disrupted nonrafts and rafts. Imaging of B cells isolated from mice fed low- or high-fat (HF) (n-3) PUFA diets showed no change in nonraft organization compared with a control diet (CD). However, confocal microscopy revealed the HF (n-3) PUFA diet disrupted lipid raft clustering and size by ~40% relative to CD. Taken together, our data from 2 different model systems suggest (n-3) PUFA have limited effects on nonrafts. The ex vivo data, which confirm previous studies with EL4 cells, provide evidence that (n-3) PUFA consumed through the diet disrupt B cell lipid raft clustering. PMID:21525263
Enriching Diet with n-3 PUFAs to Help Prevent Cardiovascular Diseases in Healthy Adults: Results from Clinical Trials.

PubMed

Manuelli, Matteo; Della Guardia, Lucio; Cena, Hellas

2017-07-18

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are believed to be important for cardiovascular health. Many investigations have been carried out in an attempt to examine the effect of n-3 PUFAs intake, in the form of supplementation or fortified foods, for the management of cardiovascular disease (CVD) and risk factors for CVD, whereas less is known about the effect on healthy individuals. The present study reviews the available literature in order to examine the relationship between n-3 PUFAs intake, either via supplementation or enriched food, and the prevention of CVD among healthy adults. Interventional clinical trials on subjects aged >18 years old with none of the established risk factors for CVD have been considered for review. n-3 PUFAs supplementation or enriched food may positively regulate triglycerides and some lipoprotein subsets, as well as several vascular and coagulation parameters, even in healthy patients, presenting no risk factors for CVD, suggesting a protective effect. Diet enrichment with omega-3 is likely to be useful in helping to lower the risk of developing CVD in healthy individuals, but still offers no strong evidence of a tangible benefit on a population level. Additional studies are needed to determine the optimal daily intake, especially to prevent the unfavorable effects of PUFAs over-consumption.
Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats.

PubMed

Sharma, Dyuti; Nkembi, Armande Subayi; Aubry, Estelle; Houeijeh, Ali; Butruille, Laura; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

2015-09-14

Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O₂, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O₂ (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O₂ (n = 30), PUFA ω-3/air (n = 30), control/O₂ (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O₂ (n = 30) or to the control/O₂ (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth.
Inadequate daily intakes of n-3 polyunsaturated fatty acids (PUFA) in the general French population of children (3-10 years) and adolescents (11-17 years): the INCA2 survey.

PubMed

Guesnet, Philippe; Tressou, Jessica; Buaud, Benjamin; Simon, Noëmie; Pasteau, Stéphane

2018-04-23

This paper deals with the dietary daily intakes of main polyunsaturated fatty acids (PUFA) in French children and adolescents. Dietary intakes of main PUFA were determined from a general French population of 1500 children (3-10 years) and adolescents (11-17 years) by using the most recent set of national robust data on food (National Survey INCA 2 performed in 2006 and 2007). Main results showed that mean daily intakes of total fat and n-6 PUFA linoleic acid (LA, 18:2n-6) were close to current recommended values for children and adolescent populations. However, 80% (children) to 90% (adolescents) of our French populations not only ingested low quantities of n-3 long-chain PUFA (docosahexaenoic (22:6n-3) and eicosapentaenoic (20:5n-3) acids) but also very low quantities of alpha-linolenic acid (ALA, 18:3n-3) at the origin of a non-balanced n-6/n-3 ratio. Inadequate consumption of EPA + DHA was also observed in subgroups of infants and adolescent who consumed more than two servings/week of fish. Such disequilibrium in PUFA dietary intakes in favor of n-6 PUFA could have adverse impact on cell membrane incorporation of long-chain n-3 PUFA and deleterious impacts on the health of children and adolescents. Promoting the consumption of both vegetable oils and margarines rich in ALA, and oily fish rich in long-chain n-3 PUFA might improve such PUFA disequilibrium.
A n-3 PUFA depletion applied to rainbow trout fry (Oncorhynchus mykiss) does not modulate its subsequent lipid bioconversion capacity.

PubMed

Mellery, Julie; Brel, Jonathan; Dort, Junio; Geay, Florian; Kestemont, Patrick; Francis, David S; Larondelle, Yvan; Rollin, Xavier

2017-01-01

Nutritional strategies are currently developed to produce farmed fish rich in n-3 long-chain PUFA (LC-PUFA) whilst replacing fish oil by plant-derived oils in aquafeeds. The optimisation of such strategies requires a thorough understanding of fish lipid metabolism and its nutritional modulation. The present study evaluated the fatty acid bioconversion capacity of rainbow trout (Oncorhynchus mykiss) fry previously depleted in n-3 PUFA through a 60-d pre-experimental feeding period with a sunflower oil-based diet (SO) followed by a 36-d experimental period during which fish were fed either a linseed oil-based diet (LO) (this treatment being called SO/LO) or a fish oil-based diet (FO) (this treatment being called SO/FO). These treatments were compared with fish continuously fed on SO, LO or FO for 96 d. At the end of the 36-d experimental period, SO/LO and SO/FO fish recovered >80 % of the n-3 LC-PUFA reported for LO and FO fish, respectively. Fish fed on LO showed high apparent in vivo elongation and desaturation activities along the n-3 biosynthesis pathway. However, at the end of the experimental period, no impact of the fish n-3 PUFA depletion was observed on apparent in vivo elongation and desaturation activities of SO/LO fish as compared with LO fish. In contrast, the fish n-3 PUFA depletion negatively modulated the n-6 PUFA bioconversion capacity of fish in terms of reduced apparent in vivo elongation and desaturation activities. The effects were similar after 10 or 36 d of the experimental period, indicating the absence of short-term effects.
Long-chain n-3 PUFA: plant v. marine sources.

PubMed

Williams, Christine M; Burdge, Graham

2006-02-01

Increasing recognition of the importance of the long-chain n-3 PUFA, EPA and DHA, to cardiovascular health, and in the case of DHA to normal neurological development in the fetus and the newborn, has focused greater attention on the dietary supply of these fatty acids. The reason for low intakes of EPA and DHA in most developed countries (0.1-0.5 g/d) is the low consumption of oily fish, the richest dietary source of these fatty acids. An important question is whether dietary intake of the precursor n-3 fatty acid, alpha-linolenic acid (alphaLNA), can provide sufficient amounts of tissue EPA and DHA by conversion through the n-3 PUFA elongation-desaturation pathway. alphaLNA is present in marked amounts in plant sources, including green leafy vegetables and commonly-consumed oils such as rape-seed and soyabean oils, so that increased intake of this fatty acid would be easier to achieve than via increased fish consumption. However, alphaLNA-feeding studies and stable-isotope studies using alphaLNA, which have addressed the question of bioconversion of alphaLNA to EPA and DHA, have concluded that in adult men conversion to EPA is limited (approximately 8%) and conversion to DHA is extremely low (<0.1%). In women fractional conversion to DHA appears to be greater (9%), which may partly be a result of a lower rate of utilisation of alphaLNA for beta-oxidation in women. However, up-regulation of the conversion of EPA to DHA has also been suggested, as a result of the actions of oestrogen on Delta6-desaturase, and may be of particular importance in maintaining adequate provision of DHA in pregnancy. The effect of oestrogen on DHA concentration in pregnant and lactating women awaits confirmation.
Protective role of n6/n3 PUFA supplementation with varying DHA/EPA ratios against atherosclerosis in mice.

PubMed

Liu, Liang; Hu, Qinling; Wu, Huihui; Xue, Yihong; Cai, Liang; Fang, Min; Liu, Zhiguo; Yao, Ping; Wu, Yongning; Gong, Zhiyong

2016-06-01

The effects of n3 polyunsaturated fatty acids (PUFA) on cardiovascular disease are controversial. We currently explored the effects of various ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on high-fat-induced atherosclerosis. In model apoE(-/-) mice, high-fat diets (HFD) were partially replaced with fish and algal oils (DHA/EPA 2:1, 1:1 and 1:2) and/or plant oils enriched in linoleic and alpha-linolenic acids with an n6/n3 ratio of 4:1. PUFA supplementation significantly reduced the atherosclerotic plaque area, serum lipid profile, inflammatory response, aortic ROS production, proinflammatory factors and scavenger receptor expression as compared to those in the HFD group. However, plant oils did not have a significant effect on the following: serum HDL-C level; aortic ABCA1, ABCG1 and LAL mRNA expression; and CD36 and LOX-1 protein expression. Compared to the plant-oil-treated group, the DHA/EPA 1:1 group had a smaller atherosclerotic plaque area, higher serum HDL-C levels and lesser CD36 and MSR-1 mRNA expression; the DHA/EPA 2:1 group had lower serum TC, LDL-C and TNF-α levels and lower aortic ROS levels. Our study suggested that n3 PUFA from animals had more potent atheroprotective effects than that from plants. Supplementation involving higher DHA/EPA ratios and an n6/n3 ratio of 4:1 was beneficial for reducing serum "bad cholesterol" and a 1:1 DHA/EPA ratio with an n6/n3 ratio of 4:1 was beneficial for improving serum "good cholesterol" and inhibiting ox-LDL uptake. Our results suggest that achieving an n6/n3 ratio of 4:1 in the diet is also important in addition to having an optimal DHA/EPA ratio. Copyright © 2016 Elsevier Inc. All rights reserved.
Effect of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation to lactating sows on growth and indicators of stress in post-weaned pig

USDA-ARS?s Scientific Manuscript database

Dietary n-3 PUFA are precursors for lipid metabolites that reduce inflammation. Two experiments were conducted to test the hypothesis that enriching the sow diet in n-3 PUFA during late gestation and throughout lactation reduces stress and inflammation, and promotes growth in weaned pigs. A protecte...
Brain histological changes in young mice submitted to diets with different ratios of n-6/n-3 polyunsaturated fatty acids during maternal pregnancy and lactation.

PubMed

Tian, Chunyu; Fan, Chaonan; Liu, Xinli; Xu, Feng; Qi, Kemin

2011-10-01

N-3 polyunsaturated fatty acids (n-3 PUFAs) are essential for brain development and function, but the appropriate quantity of dietary n-3 PUFAs and ratio of n-6/n-3 PUFAs have not been clearly determined. In this study, we investigated the effects of different dietary ratios of n-6/n-3 PUFAs on the brain structural development in mice and the expression of associated transcription factors. C57 BL/6J mice were fed with one of two categories of n-3 PUFA-containing diets (a flaxseed oil diet and a flaxseed/fish oil mixed diet) or an n-3 PUFA-deficient diet. For each of the n-3 PUFA diets, flaxseed oil or flaxseed/fish oil was combined with other oils to yield three different n-6/n-3 ratios, which ranged from 15.7:1 to 1.6:1. The feeding regimens began two months before mouse conception and continued throughout lactation for new pups. As compared with the n-3 PUFA-deficient diet, both the flaxseed oil n-3 PUFA diets and the flaxseed/fish oil n-3 PUFA diets significantly increased the expression levels of brain neuron-specific enolase, glial fibrillary acidic protein and myelin basic protein, somewhat dose-dependently, in new pup mice at 21 d and 42 d of age. The expression of PPAR-γ in the brains of pup mice was increased only at 7 d of age with the n-3 PUFA diet, and no changes in the expression of PPAR-α and PPAR-β were found among all the diet groups. These results suggest that the higher intake amount of n-3 PUFAs with a low ratio of n-6/n-3 PUFAs at about 1-2:1, supplied during both maternal pregnancy and lactation, may be more beneficial for early brain development, and PPAR-γ may act in one of the pathways by which n-3 PUFAs promote early brain development. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Cerebral asymmetry and behavioral lateralization in rats chronically lacking n-3 polyunsaturated fatty acids.

PubMed

Vancassel, Sylvie; Aïd, Sabah; Pifferi, Fabien; Morice, Elise; Nosten-Bertrand, Marika; Chalon, Sylvie; Lavialle, Monique

2005-11-15

Anatomic and functional brain lateralization underlies hemisphere specialization for cognitive and motor control, and deviations from the normal patterns of asymmetry appear to be related to behavioral deficits. Studies on n-3 polyunsaturated fatty acid (PUFA) deficiency and behavioral impairments led us to postulate that a chronic lack of n-3 PUFA can lead to changes in lateralized behavior by affecting structural or neurochemical patterns of asymmetry in motor-related brain structures. We compared the effects of a chronic n-3 PUFA deficient diet with a balanced diet on membrane phospholipid fatty acids composition and immunolabeling of choline acetyltransferase (ChAt), as a marker of cholinergic neurons, in left and right striatum of rats. Lateral motor behavior was assessed by rotation and paw preference. Control rats had an asymmetric PUFA distribution with a right behavioral preference, whereas ChAt density was symmetrical. In deficient rats, the cholinergic neuron density was 30% lower on the right side, associated with a loss of PUFA asymmetry and behavior laterality. They present higher rotation behavior, and significantly more of them failed the handedness test. These results indicate that a lack of n-3 PUFA is linked with a lateral behavior deficit, possibly leading to cognitive disturbances.
Lipoic acid prevents suppression of connective tissue proliferation in the rat liver induced by n-3 PUFAs. A pilot study.

PubMed

Arend, A; Zilmer, M; Vihalemm, T; Selstam, G; Sepp, E

2000-01-01

As previously shown, dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) suppress connective tissue proliferation in the rat liver wound concurrent with an elevated level of lipid peroxidation. The present study was undertaken to investigate the influence of alpha-lipoic acid (LA), a natural anti-oxidant, on these effects of n-3 PUFAs. Rats were fed with a commercial pellet diet (control group) or with diets enriched with 10% of sunflower oil (n-6 group) or 10% of fish oil (n-3 group) for 8 weeks followed by addition of LA to the same diets for 10 days. Then a liver thermic wound was induced and the administration of LA was continued for 6 days. The proliferation of the connective tissue, the level of lipid peroxidation and their peroxidizability and the content of prostaglandins E2 and F2alpha were measured in the liver wounds. LA prevented the suppression of connective tissue proliferation in the healing wound induced by n-3 PUFAs, avoided the increase in peroxidation of lipids, reduced peroxidizability of lipids and modulated the decrease in PGE2 and PGF2alpha. The results indicate that dietary LA may prevent the suppression of liver wound healing induced by n-3 PUFAs.
Improvement of the omega 3 index of healthy subjects does not alter the effects of dietary saturated fats or n-6PUFA on LDL profiles.

PubMed

Dias, Cintia B; Amigó, Núria; Wood, Lisa G; Mallol, Roger; Correig, Xavier; Garg, Manohar L

2017-03-01

Dietary fat composition is known to modulate circulating lipid and lipoprotein levels. Although supplementation with long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to reduce plasma triglyceride levels, the effect of the interactions between LCn-3PUFA and the major dietary fats consumed has not been previously investigated. In a randomized controlled parallel design clinical intervention, we examined the effect of diets rich in either saturated fatty acids (SFA) or omega-6 polyunsaturated fatty acids (n-6PUFA) on plasma lipid levels and lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) in subjects with an adequate omega 3 index. Twenty six healthy subjects went through a four-week pre-supplementation period with LCn-3PUFA and were then randomized to diets rich in either n-6PUFA or SFA both supplemented with LCn-3PUFA. The diet rich in n-6PUFA decreased low density lipoprotein (LDL) particle concentration (-8%, p=0.013) and LDL cholesterol (LDL-C) level (-8%, p=0.021), while the saturated fat rich diet did not affect LDL particle concentration or LDL-C levels significantly. Nevertheless, dietary saturated fatty acids increased LCn-3PUFA in plasma and tissue lipids compared with n-6PUFA, potentially reducing other cardiovascular risk factors such as inflammation and clotting tendency. Improvement on the omega 3 index of healthy subjects did not alter the known effects of dietary saturated fats and n-6PUFA on LDL profiles. Copyright © 2016 Elsevier Inc. All rights reserved.
The anxiolytic activity of n-3 PUFAs enriched egg yolk phospholipids in rat behavioral studies.

PubMed

Rutkowska, M; Słupski, W; Trocha, M; Szandruk, M; Rymaszewska, J

2016-11-02

Phospholipids play an important role in the biochemical and physiological processes of cells. An association between disturbed phospholipids metabolism in neuronal tissue and anxiety it was shown. The aim of this study was to examine the anxiolytic properties of phospholipids obtained from a new generation of eggs enriched in n-3 PUFA and its effect on locomotor activity in rat behavioral studies N-3 PUFA-enriched egg yolk phospholipids ("super lecithin") were added to the standard feed. Rats were fed by chow without (control group) or with (experimental group) addition of phospholipids. After six weeks of supplementation, the effect of phospholipids on locomotor activity in the open field test and anxiolytic properties in elevated plus maze and Vogel conflict test were examined. In the open field test the total distance traveled in the experimental group was similar to the control group. In the elevated plus maze test a six weeks phospholipids' administration significantly prolonged the time spent on the open arms by rats from experimental group compared to control group. The number of entries into the open arms was also increased but the difference was not statistically significant. The number of punished drinking water in the Vogel conflict test increased significantly in experimental versus control group. The obtained results suggest that the phospholipids isolated from n-3 PUFA enriched egg yolk have a specific anxiolytic effect, without general sedative influence.
Ratio of n-3/n-6 PUFAs and risk of breast cancer: a meta-analysis of 274135 adult females from 11 independent prospective studies

PubMed Central

2014-01-01

Background Increased ratio of n-3/n-6 polyunsaturated fatty acids (PUFAs) in diet or serum may have a protective effect on the risk of breast cancer (BC); however, the conclusions from prospective studies are still controversial. The purpose of this study is to ascertain the relationship between intake ratio of n-3/n-6 PUFAs and the risk of BC, and estimate the potential summarized dose–response trend. Methods Relevant English-language studies were identified through Cochrane Library, PubMed and EMBASE database till April 2013. Eligible prospective studies reporting the multivariate adjusted risk ratios (RRs) for association of n-3/n-6 PUFAs ratio in diet or serum with BC risk. Data extraction was conducted independently by 2 investigators; disagreements were reconciled by consensus. Study quality was assessed using the Newcastle-Ottawa scale. Study-specific RRs were combined via a random-effects model. Results Six prospective nested case–control and 5 cohort studies, involving 8,331 BC events from 274,135 adult females across different countries, were included in present study. Subjects with higher dietary intake ratio of n-3/n-6 PUFAs have a significantly lower risk of BC among study populations (pooled RR = 0.90; 95% CI: 0.82, 0.99), and per 1/10 increment of ratio in diet was associated with a 6% reduction of BC risk (pooled RR = 0.94; 95% CI: 0.90, 0.99; P for linear trend = 0.012). USA subjects with higher ratio of n-3/n-6 in serum phospholipids (PL) have a significantly lower risk of BC (pooled RR = 0.62; 95% CI: 0.39, 0.97; I2 = 0.00%; P for metaregression = 0.103; P for a permutation test = 0.100), and per 1/10 increment of ratio in serum PL was associated with 27% reduction of BC risk (pooled RR = 0.73; 95% CI: 0.59, 0.91; P for linear trend = 0.004; P for metaregression = 0.082; P for a permutation test = 0.116). Conclusions Higher intake ratio of n-3/n-6 PUFAs is associated with lower risk of BC among females, which implies an important evidence for
Association between polymorphisms in phospholipase A2 genes and the plasma triglyceride response to an n-3 PUFA supplementation: a clinical trial.

PubMed

Tremblay, Bénédicte L; Cormier, Hubert; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2015-02-21

Fish oil-derived long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma triglyceride (TG) levels. Genetic factors such as single-nucleotide polymorphisms (SNPs) found in genes involved in metabolic pathways of n-3 PUFA could be responsible for well-recognized heterogeneity in plasma TG response to n-3 PUFA supplementation. Previous studies have shown that genes in the glycerophospholipid metabolism such as phospholipase A2 (PLA2) group II, IV, and VI, demonstrate changes in their expression levels in peripheral blood mononuclear cells (PBMCs) after n-3 PUFA supplementation. A total of 208 subjects consumed 3 g/day of n-3 PUFA for 6 weeks. Plasma lipids were measured before and after the supplementation period. Five SNPs in PLA2G2A, six in PLA2G2C, eight in PLA2G2D, six in PLA2G2F, 22 in PLA2G4A, five in PLA2G6, and nine in PLA2G7 were genotyped. The MIXED Procedure for repeated measures adjusted for age, sex, BMI, and energy intake was used in order to test whether the genotype, supplementation or interaction (genotype by supplementation) were associated with plasma TG levels. The n-3 PUFA supplementation had an independent effect on plasma TG levels. Genotype effects on plasma TG levels were observed for rs2301475 in PLA2G2C, rs818571 in PLA2G2F, and rs1569480 in PLA2G4A. Genotype x supplementation interaction effects on plasma TG levels were observed for rs1805018 in PLA2G7 as well as for rs10752979, rs10737277, rs7540602, and rs3820185 in PLA2G4A. These results suggest that, SNPs in PLA2 genes may influence plasma TG levels during a supplementation with n-3 PUFA. This trial was registered at clinicaltrials.gov as NCT01343342.
Dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference.

PubMed

Jakobsen, Marianne U; Madsen, Lise; Skjøth, Flemming; Berentzen, Tina L; Halkjær, Jytte; Tjønneland, Anne; Schmidt, Erik B; Sørensen, Thorkild Ia; Kristiansen, Karsten; Overvad, Kim

2017-05-01

Background: Adding long-chain n-3 (ω-3) polyunsaturated fatty acids (PUFAs) to a rodent diet reduces fat mass and prevents the development of obesity, but evidence of a similar effect in humans is rather limited. Objectives: We investigated the associations between dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference in humans. Effect modification by the carbohydrate:protein ratio and glycemic index was also investigated. Design: A total of 29,152 participants included in the Diet, Cancer, and Health cohort were followed. Dietary intake was assessed with the use of a validated 192-item semiquantitative food-frequency questionnaire. Adipose tissue content of fatty acids was determined by gas chromatography in a random sample of the cohort ( n = 1660). Anthropometric measurements were taken at baseline and 5 y later. Associations were investigated with the use of a linear regression model. Results: For high (1.22 g/d) compared with low (0.28 g/d) total n-3 PUFA intake, the difference in 5-y weight change was 147.6 g (95% CI: -42.3, 337.5 g); P -trend = 0.088. No associations between the individual n-3 PUFAs eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were observed. Intake of n-3 PUFAs was not associated with a 5-y change in waist circumference. For high (0.16%) compared with low (0.06%) adipose tissue content of EPA, the difference in 5-y weight change was -649.6 g (95% CI: -1254.2, -44.9 g); P -trend = 0.027. No associations between total n-3 PUFA, docosapentaenoic acid, and docosahexaenoic acid and 5-y weight change were observed. Adipose tissue content of n-3 PUFAs was not associated with 5-y change in waist circumference. No effect modification by carbohydrate:protein ratio or glycemic index was found. Conclusion: Dietary intake and adipose tissue content of long-chain n-3 PUFAs were neither consistently nor appreciably associated with change in body weight
Preservation of Metabolic Flexibility in Skeletal Muscle by a Combined Use of n-3 PUFA and Rosiglitazone in Dietary Obese Mice

PubMed Central

van Schothorst, Evert M.; Bunschoten, Annelies; Flachs, Pavel; Kus, Vladimir; Kuda, Ondrej; Bardova, Kristina; Janovska, Petra; Hensler, Michal; Rossmeisl, Martin; Wang-Sattler, Rui; Prehn, Cornelia; Adamski, Jerzy; Illig, Thomas; Keijer, Jaap; Kopecky, Jan

2012-01-01

Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. This, in turn, contributes to a further damage of insulin signaling. Effectiveness of T2D treatment depends in large part on the improvement of insulin sensitivity and metabolic adaptability of the muscle, the main site of whole-body glucose utilization. We have shown previously in mice fed an obesogenic high-fat diet that a combined use of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinediones (TZDs), anti-diabetic drugs, preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether n-3 LC-PUFA could elicit additive beneficial effects on metabolic flexibility when combined with a TZD drug rosiglitazone. Adult male C57BL/6N mice were fed an obesogenic corn oil–based high-fat diet (cHF) for 8 weeks, or randomly assigned to various interventions: cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids (cHF+F), cHF with 10 mg rosiglitazone/kg diet (cHF+ROSI), cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combined intervention. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the interventions, with n-3 LC-PUFA supporting complete oxidation of fatty acids in mitochondria and the combination with n-3 LC-PUFA and rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combined use of n-3 LC-PUFA and TZDs could improve the efficacy of the therapy of obese and diabetic patients. PMID:22952760
Mitochondrial basis of the anti-arrhythmic action of lidocaine and modulation by the n-6 to n-3 PUFA ratio of cardiac phospholipids.

PubMed

Demaison, Luc; Moreau, Daniel; Clauw, Fabienne; Vergely, Catherine; Rochette, Luc

2013-08-01

The aim of this study was to evaluate the involvement of mitochondria in the mechanism of the anti-arrhythmic lidocaine. Rats were fed with a diet containing either n-6 polyunsaturated fatty acids (PUFAs, SSO group) or an equimolecular mixture of n-3 and n-6 PUFAs (FO group) for 8 weeks. The hearts were perfused according to the working mode using a medium with or without lidocaine 5 μm. They were then subjected to local ischemia (20 min) and reperfusion (30 min). Dietary n-3 PUFAs triggered the expected decrease in the n-6/n-3 PUFA ratio of cardiac phospholipids. Reperfusing the ischemic area favored the incidence of severe arrhythmias. Lidocaine treatment abolished almost completely reperfusion arrhythmias in the FO group, but did not display anti-arrhythmic properties in the SSO group. As it was indicated by measurements of the mitochondrial function, lidocaine seemed to favor mitochondrial calcium retention in the FO group, which might prevent cytosolic calcium spikes and reperfusion arrhythmias. In the SSO group, the resistance to lidocaine was associated with an aggravation of cellular damages. The mitochondrial calcium retention capacities were saturated, and lidocaine was unable to increase them, making the drug inefficient in preventing reperfusion arrhythmias. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.
All n-3 PUFA are not the same: MD simulations reveal differences in membrane organization for EPA, DHA and DPA.

PubMed

Leng, Xiaoling; Kinnun, Jacob J; Cavazos, Andres T; Canner, Samuel W; Shaikh, Saame Raza; Feller, Scott E; Wassall, Stephen R

2018-05-01

Eicosapentaenoic (EPA, 20:5), docosahexaenoic (DHA, 22:6) and docosapentaenoic (DPA, 22:5) acids are omega-3 polyunsaturated fatty acids (n-3 PUFA) obtained from dietary consumption of fish oils that potentially alleviate the symptoms of a range of chronic diseases. We focus here on the plasma membrane as a site of action and investigate how they affect molecular organization when taken up into a phospholipid. All atom MD simulations were performed to compare 1-stearoyl-2-eicosapentaenoylphosphatylcholine (EPA-PC, 18:0-20:5PC), 1-stearoyl-2-docosahexaenoylphosphatylcholine (DHA-PC, 18:0-22:6PC), 1-stearoyl-2-docosapentaenoylphosphatylcholine (DPA-PC, 18:0-22:5PC) and, as a monounsaturated control, 1-stearoyl-2-oleoylphosphatidylcholine (OA-PC, 18:0-18:1PC) bilayers. They were run in the absence and presence of 20mol% cholesterol. Multiple double bonds confer high disorder on all three n-3 PUFA. The different number of double bonds and chain length for each n-3 PUFA moderates the reduction in membrane order exerted (compared to OA-PC, S¯ CD =0.152). EPA-PC (S¯ CD =0.131) is most disordered, while DPA-PC (S¯ CD =0.140) is least disordered. DHA-PC (S¯ CD =0.139) is, within uncertainty, the same as DPA-PC. Following the addition of cholesterol, order in EPA-PC (S¯ CD =0.169), DHA-PC (S¯ CD =0.178) and DPA-PC (S¯ CD =0.182) is increased less than in OA-PC (S¯ CD =0.214). The high disorder of n-3 PUFA is responsible, preventing the n-3 PUFA-containing phospholipids from packing as close to the rigid sterol as the monounsaturated control. Our findings establish that EPA, DHA and DPA are not equivalent in their interactions within membranes, which possibly contributes to differences in clinical efficacy. Copyright © 2018 Elsevier B.V. All rights reserved.
Association between polymorphisms in the fatty acid desaturase gene cluster and the plasma triacylglycerol response to an n-3 PUFA supplementation.

PubMed

Cormier, Hubert; Rudkowska, Iwona; Paradis, Ann-Marie; Thifault, Elisabeth; Garneau, Véronique; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2012-08-01

Eicosapentaenoic and docosahexaenoic acids have been reported to have a variety of beneficial effects on cardiovascular disease risk factors. However, a large inter-individual variability in the plasma lipid response to an omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation is observed in different studies. Genetic variations may influence plasma lipid responsiveness. The aim of the present study was to examine the effects of a supplementation with n-3 PUFA on the plasma lipid profile in relation to the presence of single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster. A total of 208 subjects from Quebec City area were supplemented with 3 g/day of n-3 PUFA, during six weeks. In a statistical model including the effect of the genotype, the supplementation and the genotype by supplementation interaction, SNP rs174546 was significantly associated (p = 0.02) with plasma triglyceride (TG) levels, pre- and post-supplementation. The n-3 supplementation had an independent effect on plasma TG levels and no significant genotype by supplementation interaction effects were observed. In summary, our data support the notion that the FADS gene cluster is a major determinant of plasma TG levels. SNP rs174546 may be an important SNP associated with plasma TG levels and FADS1 gene expression independently of a nutritional intervention with n-3 PUFA.
Association between Polymorphisms in the Fatty Acid Desaturase Gene Cluster and the Plasma Triacylglycerol Response to an n-3 PUFA Supplementation

PubMed Central

Cormier, Hubert; Rudkowska, Iwona; Paradis, Ann-Marie; Thifault, Elisabeth; Garneau, Véronique; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2012-01-01

Eicosapentaenoic and docosahexaenoic acids have been reported to have a variety of beneficial effects on cardiovascular disease risk factors. However, a large inter-individual variability in the plasma lipid response to an omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation is observed in different studies. Genetic variations may influence plasma lipid responsiveness. The aim of the present study was to examine the effects of a supplementation with n-3 PUFA on the plasma lipid profile in relation to the presence of single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster. A total of 208 subjects from Quebec City area were supplemented with 3 g/day of n-3 PUFA, during six weeks. In a statistical model including the effect of the genotype, the supplementation and the genotype by supplementation interaction, SNP rs174546 was significantly associated (p = 0.02) with plasma triglyceride (TG) levels, pre- and post-supplementation. The n-3 supplementation had an independent effect on plasma TG levels and no significant genotype by supplementation interaction effects were observed. In summary, our data support the notion that the FADS gene cluster is a major determinant of plasma TG levels. SNP rs174546 may be an important SNP associated with plasma TG levels and FADS1 gene expression independently of a nutritional intervention with n-3 PUFA. PMID:23016130
Combination of n-3 polyunsaturated fatty acids reduces atherogenesis in apolipoprotein E-deficient mice by inhibiting macrophage activation.

PubMed

Takashima, Akira; Fukuda, Daiju; Tanaka, Kimie; Higashikuni, Yasutomi; Hirata, Yoichiro; Nishimoto, Sachiko; Yagi, Shusuke; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Taketani, Yutaka; Shimabukuro, Michio; Sata, Masataka

2016-11-01

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are major components of n-3 polyunsaturated fatty acids (n-3 PUFAs) which inhibit atherogenesis, although few studies have examined the effects of the combination of EPA and DHA on atherogenesis. The aim of this study was to investigate whether DHA has additional anti-atherosclerotic effects when combined with EPA. Male 8-week-old apolipoprotein E-deficient (Apoe -/- ) mice were fed a western-type diet supplemented with different amounts of EPA and DHA; EPA (2.5%, w/w), low-dose EPA + DHA (2.5%, w/w), or high-dose EPA + DHA (5%, w/w) for 20 weeks. The control group was fed a western-type diet containing no n-3 PUFA. Histological and gene expression analysis were performed in atherosclerotic lesions in the aorta. To address the mechanisms, RAW264.7 cells were used. All n-3 PUFA treatments significantly attenuated the development and destabilization of atherosclerotic plaques compared with the control. The anti-atherosclerotic effects were enhanced in the high-dose EPA + DHA group (p < 0.001), whereas the pure EPA group and low-dose EPA + DHA group showed similar results. EPA and DHA additively attenuated the expression of inflammatory molecules in RAW264.7 cells stimulated with LPS. DHA or EPA + DHA suppressed LPS-induced toll-like receptor 4 (TLR4) expression in lipid rafts on RAW264.7 cells (p < 0.05). Lipid raft disruption by methyl-β-cyclodextrin suppressed mRNA expression of inflammatory molecules in LPS-stimulated macrophages. n-3 PUFAs suppressed atherogenesis. DHA combined with EPA had additional anti-inflammatory effects and inhibited atherogenesis in Apoe -/- mice. The reduction of TLR4 expression in lipid rafts in macrophages by DHA might be involved in this mechanism, at least partially. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Higher Plasma Phospholipid n–3 PUFAs, but Lower n–6 PUFAs, Are Associated with Lower Pulse Wave Velocity among Older Adults123

PubMed Central

Reinders, Ilse; Murphy, Rachel A; Song, Xiaoling; Mitchell, Gary F; Visser, Marjolein; Cotch, Mary Frances; Garcia, Melissa E; Launer, Lenore J; Eiriksdottir, Gudny; Gudnason, Vilmundur; Harris, Tamara B; Brouwer, Ingeborg A

2015-01-01

Background: Higher intake of polyunsaturated fatty acids (PUFAs) and higher circulating PUFAs are associated with lower cardiovascular disease (CVD) risk. The positive influence of PUFAs might be via lowering arterial stiffness, resulting in a better CVD risk profile; however, studies investigating circulating PUFAs in relation to arterial stiffness in a general population are limited. Objective: We investigated the associations of plasma phospholipid n–3 (ω-3) and n–6 PUFAs and fish oil intake with arterial stiffness. Methods: We used data from a subgroup of the Age, Gene/Environment Susceptibility–Reykjavik (AGES-Reykjavik) Study (n = 501, 75.0 ± 4.96 y, 46% men), a population-based study of community-dwelling older adults. Plasma phospholipid PUFAs were measured by GC at baseline, and fish oil intake was assessed at 3 time points: early life (ages 14–19 y), midlife (ages 40–50 y), and late life (ages 66–96 y, AGES-Reykjavik baseline) with the use of a validated food-frequency questionnaire. Arterial stiffness was determined as carotid–femoral pulse wave velocity (cf-PWV) with the use of an electrocardiogram after a mean follow-up of 5.2 ± 0.3 y. Regression coefficients (95% CIs), adjusted for demographics, follow-up time, risk factors, cholesterol, triglycerides, and serum vitamin D, were calculated by linear regression per SD increment in PUFAs. Results: Plasma total n–3 PUFAs, eicosapentaenoic acid, and docosahexaenoic acid were associated with lower cf-PWV [β (95% CI): −0.036 (−0.064, −0.008); −0.031 (−0.059, −0.003); −0.036 (−0.064, −0.009), respectively]. In contrast, plasma total n–6 PUFAs and linoleic acid were associated with higher cf-PWV [0.035 (0.009, 0.061) and 0.034 (0.008, 0.059)]. Regular fish oil consumption at early-, mid-, and late-life was not associated with cf-PWV. Conclusions: Our results show a positive association between plasma n–6 PUFAs and arterial stiffness, and suggest that higher
Clinical Benefits of n-3 PUFA and ɤ-Linolenic Acid in Patients with Rheumatoid Arthritis.

PubMed

Veselinovic, Mirjana; Vasiljevic, Dragan; Vucic, Vesna; Arsic, Aleksandra; Petrovic, Snjezana; Tomic-Lucic, Aleksandra; Savic, Maja; Zivanovic, Sandra; Stojic, Vladislava; Jakovljevic, Vladimir

2017-03-25

(1) Background: Marine n -3 polyunsaturated fatty acids (PUFA) and ɤ-linolenic acid (GLA) are well-known anti-inflammatory agents that may help in the treatment of inflammatory disorders. Their effects were examined in patients with rheumatoid arthritis; (2) Methods: Sixty patients with active rheumatoid arthritis were involved in a prospective, randomized trial of a 12 week supplementation with fish oil (group I), fish oil with primrose evening oil (group II), or with no supplementation (group III). Clinical and laboratory evaluations were done at the beginning and at the end of the study; (3) Results: The Disease Activity Score 28 (DAS 28 score), number of tender joints and visual analogue scale (VAS) score decreased notably after supplementation in groups I and II ( p < 0.001). In plasma phospholipids the n -6/ n -3 fatty acids ratio declined from 15.47 ± 5.51 to 10.62 ± 5.07 ( p = 0.005), and from 18.15 ± 5.04 to 13.50 ± 4.81 ( p = 0.005) in groups I and II respectively. The combination of n -3 PUFA and GLA (group II) increased ɤ-linolenic acid (0.00 ± 0.00 to 0.13 ± 0.11, p < 0.001), which was undetectable in all groups before the treatments; (4) Conclusion: Daily supplementation with n -3 fatty acids alone or in combination with GLA exerted significant clinical benefits and certain changes in disease activity.
Impact of maternal n-3 polyunsaturated fatty acid deficiency on dendritic arbor morphology and connectivity of developing Xenopus laevis central neurons in vivo.

PubMed

Igarashi, Miki; Santos, Rommel A; Cohen-Cory, Susana

2015-04-15

Docosahexaenoic acid (DHA, 22:6n-3) is an essential component of the nervous system, and maternal n-3 polyunsaturated fatty acids (PUFAs) are an important source for brain development. Here, the impact of DHA on developing central neurons was examined using an accessible in vivo model. Xenopus laevis embryos from adult female frogs fed n-3 PUFA-adequate or deficient diets were analyzed every 10 weeks for up to 60 weeks, when frogs were then switched to a fish oil-supplemented diet. Lipid analysis showed that DHA was significantly reduced both in oocytes and tadpoles 40 weeks after deprivation, and brain DHA was reduced by 57% at 60 weeks. In vivo imaging of single optic tectal neurons coexpressing tdTomato and PSD-95-GFP revealed that neurons were morphologically simpler in tadpoles from frogs fed the deficient diet compared with the adequate diet. Tectal neurons had significantly fewer dendrite branches and shorter dendritic arbor over a 48 h imaging period. Postsynaptic cluster number and density were lower in neurons deprived of n-3 PUFA. Moreover, changes in neuronal morphology correlated with a 40% decrease in the levels of BDNF mRNA and mature protein in the brain, but not in TrkB. Importantly, switching to a fish oil-supplemented diet induced a recovery in DHA content in the frog embryos within 20 weeks and diminished the deprivation effects observed on tectal neurons of Stage 45 tadpoles. Consequently, our results indicate that DHA impacts dendrite maturation and synaptic connectivity in the developing brain, and it may be involved in neurotrophic support by BDNF. Copyright © 2015 the authors 0270-6474/15/356079-14$15.00/0.
Application of Silver Ion High-Performance Liquid Chromatography for Quantitative Analysis of Selected n-3 and n-6 PUFA in Oil Supplements.

PubMed

Czajkowska-Mysłek, Anna; Siekierko, Urszula; Gajewska, Magdalena

2016-04-01

The aim of this study was to develop a simple method for simultaneous determination of selected cis/cis PUFA-LNA (18:2), ALA (18:3), GLA (18:3), EPA (20:5), and DHA (22:6) by silver ion high-performance liquid chromatography coupled to a diode array detector (Ag-HPLC-DAD). The separation was performed on three Luna SCX Silver Loaded columns connected in series maintained at 10 °C with isocratic elution by 1% acetonitrile in n-hexane. The applied chromatographic system allowed a baseline separation of standard mixture of n-3 and n-6 fatty acid methyl esters containing LNA, DHA, and EPA and partial separation of ALA and GLA positional isomers. The method was validated by means of linearity, precision, stability, and recovery. Limits of detection (LOD) for considered PUFA standard solutions ranged from 0.27 to 0.43 mg L(-1). The developed method was used to evaluate of n-3 and n-6 fatty acids contents in plant and fish softgel oil capsules, results were compared with reference GC-FID based method.
Dietary n-3 PUFA affect TcR-mediated activation of purified murine T cells and accessory cell function in co-cultures

PubMed Central

CHAPKIN, R S; ARRINGTON, J L; APANASOVICH, T V; CARROLL, R J; MCMURRAY, D N

2002-01-01

Diets enriched in n-3 polyunsaturated fatty acids (PUFA) suppress several functions of murine splenic T cells by acting directly on the T cells and/or indirectly on accessory cells. In this study, the relative contribution of highly purified populations of the two cell types to the dietary suppression of T cell function was examined. Mice were fed diets containing different levels of n-3 PUFA; safflower oil (SAF; control containing no n-3 PUFA), fish oil (FO) at 2% and 4%, or 1% purified docosahexaenoic acid (DHA) for 2 weeks. Purified (>90%) T cells were obtained from the spleen, and accessory cells (>95% adherent, esterase-positive) were obtained by peritoneal lavage. Purified T cells or accessory cells from each diet group were co-cultured with the alternative cell type from every other diet group, yielding a total of 16 different co-culture combinations. The T cells were stimulated with either concanavalin A (ConA) or antibodies to the T cell receptor (TcR)/CD3 complex and the costimulatory molecule CD28 (αCD3/αCD28), and proliferation was measured after four days. Suppression of T cell proliferation in the co-cultures was dependent upon the dose of dietary n-3 PUFA fed to mice from which the T cells were derived, irrespective of the dietary treatment of accessory cell donors. The greatest dietary effect was seen in mice consuming the DHA diet (P = 0·034 in the anova; P = 0·0053 in the Trend Test), and was observed with direct stimulation of the T cell receptor and CD28 costimulatory ligand, but not with ConA. A significant dietary effect was also contributed accessory cells (P = 0·033 in the Trend Test). We conclude that dietary n-3 PUFA affect TcR-mediated by T cell activation by both direct and indirect (accessory cell) mechanisms. PMID:12296847
PUFA and LC-PUFA intake during the first year of life: can dietary practice achieve a guideline diet?

PubMed

Schwartz, J; Dube, K; Alexy, U; Kalhoff, H; Kersting, M

2010-02-01

An appropriate supply of n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) during early childhood may enhance cognitive development. Little attention is paid to the fatty acid (FA) supply during the complementary feeding period. We examined the polyunsaturated fatty acids (PUFAs) and LC-PUFAs pattern in dietary practice of two study groups and evaluated the results against the present Dietary Guidelines in Germany. The food consumption and FA pattern of dietary practice in subjects from two prospective studies (n=102 and n=184, respectively) at the age of 3, 6 and 9 months was assessed by weighed diet records, and changes during the first year of life were compared with the food-based dietary guidelines for the first year of life. Dietary practice in the complementary feeding period was clearly dominated by commercial food products. The FA composition in dietary practice was different from the Guideline Diet and the ratio of n-6/n-3 PUFAs was less favorable. Consumption of breast milk or formula was still of major importance for the intake of LC-PUFAs in the complementary feeding period. LC-PUFAs are predominantly provided by breast milk and formula during the first year of life and consequently decrease when milk consumption decreases. For compensation, commercial complementary food might come closer to the Guideline Diet by lowering the n-6/n-3 PUFA ratio through appropriate vegetable oil along with an increase in total fat content up to the legal limit.
Increased blood pressure later in life may be associated with perinatal n-3 fatty acid deficiency.

PubMed

Armitage, James A; Pearce, Adrian D; Sinclair, Andrew J; Vingrys, Algis J; Weisinger, Richard S; Weisinger, Harrison S

2003-04-01

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Previous work in both animals and humans with high blood pressure has demonstrated the antihypertensive effects of n-3 polyunsaturated fatty acids (PUFA), although it is not known whether these nutrients are effective in preventing hypertension. The predominant n-3 PUFA in the mammalian nervous system, docosahexaenoic acid (DHA), is deposited into synaptic membranes at a high rate during the perinatal period, and recent observations indicate that the perinatal environment is important for the normal development of blood pressure control. This study investigated the importance of perinatal n-3 PUFA supply in the control of blood pressure in adult Sprague-Dawley rats. Pregnant rat dams were fed semisynthetic diets that were either deficient in (DEF) or supplemented with (CON) n-3 PUFA. Offspring were fed the same diets as their mothers until 9 wk; then, half of the rats from each group were crossed over to the opposite diet creating four groups, i.e., CON-CON; CON-DEF; DEF-DEF, DEF-CON. Mean arterial blood pressures (MAP) were measured directly, at 33 wk of age, by cannulation of the femoral artery. The phospholipid fatty acid profile of the hypothalamic region was determined by capillary gas-liquid chromatography. The tissue phospholipid fatty acid profile reflected the diet that the rats were consuming at the time of testing. Both groups receiving DEF after 9 wk of age (i.e., DEF-DEF and CON-DEF) had similar profiles with a reduction in DHA levels of 30%, compared with rats receiving CON (i.e., CON-CON and DEF-CON). DEF-DEF rats had significantly raised MAP compared with all other groups, with differences as great as 17 mm Hg. DEF-CON rats had raised MAP compared with CON-CON rats, and DEF-DEF rats had higher MAP than CON-DEF rats, despite the fact that their respective fatty acid profiles were not different. These findings indicate that inadequate levels of DHA in the perinatal

Liver conversion of docosahexaenoic and arachidonic acids from their 18-carbon precursors in rats on a DHA-free but α-LNA-containing n-3 PUFA adequate diet.

PubMed

Gao, Fei; Kim, Hyung-Wook; Igarashi, Miki; Kiesewetter, Dale; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I

2011-01-01

The long-chain polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6), are critical for health. These PUFAs can be synthesized in liver from their plant-derived precursors, α-linolenic acid (α-LNA, 18:3n-3) and linoleic acid (LA, 18:2n-6). Vegetarians and vegans may have suboptimal long-chain n-3 PUFA status, and the extent of the conversion of α-LNA to EPA and DHA by the liver is debatable. We quantified liver conversion of DHA and other n-3 PUFAs from α-LNA in rats fed a DHA-free but α-LNA (n-3 PUFA) adequate diet, and compared results to conversion of LA to AA. [U-(13)C]LA or [U-(13)C]α-LNA was infused intravenously for 2h at a constant rate into unanesthetized rats fed a DHA-free α-LNA adequate diet, and published equations were used to calculate kinetic parameters. The conversion coefficient k(⁎) of DHA from α-LNA was much higher than for AA from LA (97.2×10(-3) vs. 10.6×10(-3)min(-1)), suggesting that liver elongation-desaturation is more selective for n-3 PUFA biosynthesis on a per molecule basis. The net daily secretion rate of DHA, 20.3μmol/day, exceeded the reported brain DHA consumption rate by 50-fold, suggesting that the liver can maintain brain DHA metabolism with an adequate dietary supply solely of α-LNA. This infusion method could be used in vegetarians or vegans to determine minimal daily requirements of EPA and DHA in humans. Published by Elsevier B.V.
Omega-3 Index and Anti-Arrhythmic Potential of Omega-3 PUFAs

PubMed Central

Tribulova, Narcis; Szeiffova Bacova, Barbara; Egan Benova, Tamara; Knezl, Vladimir; Barancik, Miroslav; Slezak, Jan

2017-01-01

Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. The purpose of this updated review is to focus on the novel cellular and molecular effects of omega-3 PUFAs, in the context of the mechanisms and factors involved in the development of cardiac arrhythmias; to provide results of the most recent studies on the omega-3 PUFA anti-arrhythmic efficacy and to discuss the lack of the benefit in relation to omega-3 PUFA status. The evidence is in the favor of omega-3 PUFA acute and long-term treatment, perhaps with mitochondria-targeted antioxidants. However, for a more objective evaluation of the anti-arrhythmic potential of omega-3 PUFAs in clinical trials, it is necessary to monitor the basal pre-interventional omega-3 status of individuals, i.e., red blood cell content, omega-3 index and free plasma levels. In the view of evidence-based medicine, it seems to be crucial to aim to establish new approaches in the prevention of cardiac arrhythmias and associated morbidity and mortality that comes with these conditions. PMID:29084142
Omega-3 Index and Anti-Arrhythmic Potential of Omega-3 PUFAs.

PubMed

Tribulova, Narcis; Szeiffova Bacova, Barbara; Egan Benova, Tamara; Knezl, Vladimir; Barancik, Miroslav; Slezak, Jan

2017-10-30

Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. The purpose of this updated review is to focus on the novel cellular and molecular effects of omega-3 PUFAs, in the context of the mechanisms and factors involved in the development of cardiac arrhythmias; to provide results of the most recent studies on the omega-3 PUFA anti-arrhythmic efficacy and to discuss the lack of the benefit in relation to omega-3 PUFA status. The evidence is in the favor of omega-3 PUFA acute and long-term treatment, perhaps with mitochondria-targeted antioxidants. However, for a more objective evaluation of the anti-arrhythmic potential of omega-3 PUFAs in clinical trials, it is necessary to monitor the basal pre-interventional omega-3 status of individuals, i.e., red blood cell content, omega-3 index and free plasma levels. In the view of evidence-based medicine, it seems to be crucial to aim to establish new approaches in the prevention of cardiac arrhythmias and associated morbidity and mortality that comes with these conditions.
A comparison of heart rate variability, n-3 PUFA status and lipid mediator profile in age- and BMI-matched middle-aged vegans and omnivores.

PubMed

Pinto, Ana M; Sanders, Thomas A B; Kendall, Alexandra C; Nicolaou, Anna; Gray, Robert; Al-Khatib, Haya; Hall, Wendy L

2017-03-01

Low heart rate variability (HRV) predicts sudden cardiac death. Long-chain (LC) n-3 PUFA (C20-C22) status is positively associated with HRV. This cross-sectional study investigated whether vegans aged 40-70 years (n 23), whose diets are naturally free from EPA (20 : 5n-3) and DHA (22 : 6n-3), have lower HRV compared with omnivores (n 24). Proportions of LC n-3 PUFA in erythrocyte membranes, plasma fatty acids and concentrations of plasma LC n-3 PUFA-derived lipid mediators were significantly lower in vegans. Day-time interbeat intervals (IBI), adjusted for physical activity, age, BMI and sex, were significantly shorter in vegans compared with omnivores (mean difference -67 ms; 95 % CI -130, -3·4, P50 % and high-frequency power) were similarly lower in vegans, with no differences during sleep. In conclusion, vegans have higher 24 h SDNN, but lower day-time HRV and shorter day-time IBI relative to comparable omnivores. Vegans may have reduced availability of precursor markers for pro-resolving lipid mediators; it remains to be determined whether there is a direct link with impaired cardiac function in populations with low-n-3 status.
Fish or n3-PUFA intake and body composition: a systematic review and meta-analysis.

PubMed

Bender, N; Portmann, M; Heg, Z; Hofmann, K; Zwahlen, M; Egger, M

2014-08-01

Obesity is a major public health issue and an important contributor to the global burden of chronic disease and disability. Studies indicate that fish and omega-3 polyunsaturated fatty acids (n3-PUFA) supplements may help prevent cardiovascular and metabolic diseases. However, the effect of fish oil on body composition is still uncertain, so we performed a systematic review of randomized controlled trials and the first meta-analysis on the association between fish or fish oil intake and body composition measures. We found evidence that participants taking fish or fish oil lost 0.59 kg more body weight than controls (95% confidence interval [CI]: -0.96 to -0.21). Treatment groups lost 0.24 kg m(-2) (body mass index) more than controls (-0.40 to -0.08), and 0.49 % more body fat than controls (-0.97 to -0.01). Fish or fish oil reduced waist circumference by 0.81 cm (-1.34 to -0.28) compared with control. There was no difference for fat mass and lean body mass. Further research is needed to confirm or refute our findings and to reveal possible mechanisms by which n3-PUFAs might reduce weight. © 2014 The Authors. obesity reviews © 2014 World Obesity.
Long-chain n-3 PUFA supplied by the usual diet decrease plasma stearoyl-CoA desaturase index in non-hypertriglyceridemic older adults at high vascular risk.

PubMed

Pérez-Heras, Ana M; Mayneris-Perxachs, Jordi; Cofán, Montserrat; Serra-Mir, Mercè; Castellote, Ana I; López-Sabater, Carmen; Fitó, Montserrat; Salas-Salvadó, Jordi; Martínez-González, Miguel-Ángel; Corella, Dolores; Estruch, Ramon; Ros, Emilio; Sala-Vila, Aleix

2018-02-01

The activity of stearoyl-CoA desaturase-1 (SCD1), the central enzyme in the synthesis of monounsaturated fatty acids (MUFA), has been associated with de novo lipogenesis. In experimental models SCD1 is down-regulated by polyunsaturated fatty acids (PUFA), but clinical studies are scarce. The effect of long-chain n-3 PUFA (LCn-3PUFA) supplied by the regular diet, in the absence of fatty fish or fish oil supplementation, remains to be explored. We related 1-y changes in plasma SCD1 index, as assessed by the C16:1n-7/C16:0 ratio, to both adiposity traits and nutrient intake changes in a sub-cohort (n = 243) of non-hypertriglyceridemic subjects of the PREDIMED (PREvención con DIeta MEDiterranea) trial. After adjustment for confounders, including changes in fasting triglycerides, plasma SCD1 index increased in parallel with body weight (0.221 [95% confidence interval, 0.021 to 0.422], P = 0.031) and BMI (0.115 [0.027 to 0.202], P = 0.011). Additionally, dietary LCn-3PUFA (but not MUFA or plant-derived PUFA) were associated with decreased plasma SCD1 index (-0.544 [-1.044 to -0.043], P = 0.033, for each 1 g/d-increase in LCn-3PUFA). No associations were found for other food groups, but there was a trend for fatty fish intake (-0.083 [-0.177 to 0.012], P = 0.085, for each 10 g/d-increase). Our data add clinical evidence on the down-regulation of plasma SCD1 index by LCn-3PUFA in the context of realistic changes in fish consumption in the customary, non-supplemented diet. http://www.Controlled-trials.com/ISRCTN35739639. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Characterisation of the vasodilation effects of DHA and EPA, n-3 PUFAs (fish oils), in rat aorta and mesenteric resistance arteries.

PubMed

Limbu, Roshan; Cottrell, Graeme S; McNeish, Alister J

2018-01-01

Increasing evidence suggests that the omega-3 polyunsaturated acids (n-3 PUFA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are beneficial to cardiovascular health, promoting relaxation of vascular smooth muscle cells and vasodilation. Numerous studies have attempted to study these responses, but to date there has not been a systematic characterisation of both DHA and EPA mediated vasodilation in conduit and resistance arteries. Therefore, we aimed to fully characterise the n-3 PUFA-induced vasodilation pathways in rat aorta and mesenteric artery. Wire myography was used to measure the vasomotor responses of freshly dissected rat mesenteric artery and aorta. Arteries were pre-constricted with U46619 and cumulative concentrations of either DHA or EPA (10 nM-30 μM) were added. The mechanisms by which n-3 PUFA relaxed arteries were investigated using inhibitors of vasodilator pathways, which include: nitric oxide synthase (NOS; L-NAME), cycloxygenase (COX; indomethacin), cytochrome P450 epoxygenase (CYP450; clotrimazole); and calcium-activated potassium channels (KCa), SKCa (apamin), IKCa (TRAM-34) and BKCa (paxilline). Both DHA- and EPA-induced relaxations were partially inhibited following endothelium removal in rat mesenteric arteries. Similarly, in aorta EPA-induced relaxation was partially suppressed due to endothelium removal. CYP450 also contributed to EPA-induced relaxation in mesenteric artery. Inhibition of IKCa partially attenuated DHA-induced relaxation in aorta and mesenteric artery along with EPA-induced relaxation in mesenteric artery. Furthermore, this inhibition of DHA- and EPA-induced relaxation was increased following the additional blockade of BKCa in these arteries. This study provides evidence of heterogeneity in the vasodilation mechanisms of DHA and EPA in different vascular beds. Our data also demonstrates that endothelium removal has little effect on relaxations produced by either PUFA. We demonstrate IKCa and BKCa are
Characterisation of the vasodilation effects of DHA and EPA, n-3 PUFAs (fish oils), in rat aorta and mesenteric resistance arteries

PubMed Central

Limbu, Roshan; Cottrell, Graeme S.

2018-01-01

Background and purpose Increasing evidence suggests that the omega-3 polyunsaturated acids (n-3 PUFA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are beneficial to cardiovascular health, promoting relaxation of vascular smooth muscle cells and vasodilation. Numerous studies have attempted to study these responses, but to date there has not been a systematic characterisation of both DHA and EPA mediated vasodilation in conduit and resistance arteries. Therefore, we aimed to fully characterise the n-3 PUFA-induced vasodilation pathways in rat aorta and mesenteric artery. Methods Wire myography was used to measure the vasomotor responses of freshly dissected rat mesenteric artery and aorta. Arteries were pre-constricted with U46619 and cumulative concentrations of either DHA or EPA (10 nM-30 μM) were added. The mechanisms by which n-3 PUFA relaxed arteries were investigated using inhibitors of vasodilator pathways, which include: nitric oxide synthase (NOS; L-NAME), cycloxygenase (COX; indomethacin), cytochrome P450 epoxygenase (CYP450; clotrimazole); and calcium-activated potassium channels (KCa), SKCa (apamin), IKCa (TRAM-34) and BKCa (paxilline). Results Both DHA- and EPA-induced relaxations were partially inhibited following endothelium removal in rat mesenteric arteries. Similarly, in aorta EPA-induced relaxation was partially suppressed due to endothelium removal. CYP450 also contributed to EPA-induced relaxation in mesenteric artery. Inhibition of IKCa partially attenuated DHA-induced relaxation in aorta and mesenteric artery along with EPA-induced relaxation in mesenteric artery. Furthermore, this inhibition of DHA- and EPA-induced relaxation was increased following the additional blockade of BKCa in these arteries. Conclusions This study provides evidence of heterogeneity in the vasodilation mechanisms of DHA and EPA in different vascular beds. Our data also demonstrates that endothelium removal has little effect on relaxations produced by
Higher PUFA and n-3 PUFA, conjugated linoleic acid, α-tocopherol and iron, but lower iodine and selenium concentrations in organic milk: a systematic literature review and meta- and redundancy analyses.

PubMed

Średnicka-Tober, Dominika; Barański, Marcin; Seal, Chris J; Sanderson, Roy; Benbrook, Charles; Steinshamn, Håvard; Gromadzka-Ostrowska, Joanna; Rembiałkowska, Ewa; Skwarło-Sońta, Krystyna; Eyre, Mick; Cozzi, Giulio; Larsen, Mette Krogh; Jordon, Teresa; Niggli, Urs; Sakowski, Tomasz; Calder, Philip C; Burdge, Graham C; Sotiraki, Smaragda; Stefanakis, Alexandros; Stergiadis, Sokratis; Yolcu, Halil; Chatzidimitriou, Eleni; Butler, Gillian; Stewart, Gavin; Leifert, Carlo

2016-03-28

Demand for organic milk is partially driven by consumer perceptions that it is more nutritious. However, there is still considerable uncertainty over whether the use of organic production standards affects milk quality. Here we report results of meta-analyses based on 170 published studies comparing the nutrient content of organic and conventional bovine milk. There were no significant differences in total SFA and MUFA concentrations between organic and conventional milk. However, concentrations of total PUFA and n-3 PUFA were significantly higher in organic milk, by an estimated 7 (95 % CI -1, 15) % and 56 (95 % CI 38, 74) %, respectively. Concentrations of α-linolenic acid (ALA), very long-chain n-3 fatty acids (EPA+DPA+DHA) and conjugated linoleic acid were also significantly higher in organic milk, by an 69 (95 % CI 53, 84) %, 57 (95 % CI 27, 87) % and 41 (95 % CI 14, 68) %, respectively. As there were no significant differences in total n-6 PUFA and linoleic acid (LA) concentrations, the n-6:n-3 and LA:ALA ratios were lower in organic milk, by an estimated 71 (95 % CI -122, -20) % and 93 (95 % CI -116, -70) %. It is concluded that organic bovine milk has a more desirable fatty acid composition than conventional milk. Meta-analyses also showed that organic milk has significantly higher α-tocopherol and Fe, but lower I and Se concentrations. Redundancy analysis of data from a large cross-European milk quality survey indicates that the higher grazing/conserved forage intakes in organic systems were the main reason for milk composition differences.
Cardioprotective Effects of ω-3 PUFAs in Chronic Kidney Disease

PubMed Central

Lee, Su Mi

2013-01-01

The prevalence rate of chronic kidney disease (CKD) is increasing worldwide, and cardiovascular disease (CVD) is a main cause of death in patients with CKD. The high incidence of CVD in CKD patients is related to chronic inflammation, dyslipidemia, malnutrition, atherosclerosis, and vascular calcification. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been shown to reduce the risk of CVD. In this paper, we review the beneficial effects of ω-3 PUFAs on CVD and the possible cardioprotective mechanisms of ω-3 PUFAs in CKD patients by determining the effect of ω-3 PUFAs in the general population. ω-3 PUFAs have several cardioprotective benefits, such as reducing inflammation, decreasing oxidative stress, inhibiting platelet activity, exerting antiarrhythmic effects, and improving triglyceride levels, in the general population and patients with CKD. Modifications of erythrocyte membrane fatty acid content, including an increased ω-3 index and decreased oleic acid, after ω-3 PUFAs supplementation are important changes related to CVD risk reduction in the general population and patients with CKD. Further basic and clinical studies are essential to confirm the effects of ω-3 PUFAs on vitamin D activation, vascular calcification prevention, cardiovascular events, and mortality in CKD patients. PMID:23653897
The effect of n-3 PUFAs on circulating adiponectin and leptin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Farimani, Azam Rezaei; Hariri, Mitra; Azimi-Nezhad, Mohsen; Borji, Abasalt; Zarei, Sadegh; Hooshmand, Elham

2018-02-16

N-3 PUFAs can potentially influence levels of inflammatory and non-inflammatory adipokines. Given the contradictory effects of n-3 PUFAs on serum levels of adipokines in type 2 diabetes, we conducted a systematic review and meta-analysis study of randomized placebo-controlled clinical trials that examined the effects of n-3 PUFAs on serum levels of leptin and adiponectin in patients with type 2 diabetes. The electronic databases, without regard to language restrictions including PubMed/Medline, Google Scholar, SCOPUS and ISI Web of Science until August 2017, were used to identify randomized controlled trials that assessed the effect of n-3 PUFAs on serum leptin and adiponectin concentrations in type 2 diabetes. Outcomes were extracted based on the mean ± SD as effect size at baseline and end of the intervention. Between-study heterogeneity was evaluated by the I 2 estimates and their 95% CIs. Funnel plot asymmetry was used to investigate the existence of publication bias. Stata software and Review Manager were used for statistical data analysis. Data from 10 eligible articles involved 494 subjects with type 2 diabetes mellitus (intervention groups = 254 and control groups = 240), with age between 44 and 70 years, treated with doses of 0.52-7.4 g/day n-3 PUFAs. Adiponectin concentration nonsignificantly increased by a MD = 0.17 µg/mL (95% CI - 0.11, 0.44). Also, leptin concentration nonsignificantly reduced by a MD = - 0.31 ng/mL (95% CI - 0.69, 0.07). Plant and marine sources of n-3 PUFAs can modify serum leptin and adiponectin levels by increasing adiponectin and decreasing leptin levels in patients with type 2 diabetes. Due to some limitations in this study, further studies are needed to reach a definitive conclusion about the effect of n-3 PUFAs on the levels of leptin and adiponectin in T2DM.
Lifelong intake of flaxseed or menhaden oil to provide varying n-6 to n-3 PUFA ratios modulate bone microarchitecture during growth, but not after OVX in Sprague-Dawley rats.

PubMed

Longo, Amanda B; Sullivan, Philip J; Peters, Sandra J; LeBlanc, Paul J; Wohl, Gregory R; Ward, Wendy E

2017-08-01

Skeletal health is a lifelong process impacted by environmental factors, including nutrient intake. The n-3 source and PUFA ratio affect bone health in growing rats, or following ovariectomy (OVX), but no study has investigated the longitudinal effect of PUFA-supplementation throughout these periods of bone development. One-month-old, Sprague-Dawley rats (n = 98) were randomized to receive one of four diets from 1 through 6 months of age. Diets were modified from AIN-93G to contain a varying amount and source of n-3 (flaxseed versus menhaden oil) to provide an n-6 to n-3 ratio of 10:1 or 5:1. At 3 (prior to SHAM or OVX) and 6 months of age, bone microarchitecture of the tibia was quantified using in vivo micro-computed tomography (SkyScan 1176, Bruker microCT). Providing 5:1 (flaxseed) resulted in lower trabecular thickness and medullary area and greater cortical area fraction during growth compared to diets with a 10:1 PUFA ratio, but many of these differences were not apparent following OVX. PUFA-supplementation at levels attainable in human diet modulates some bone structure outcomes during periods of growth, but is not an adequate strategy for the prevention of OVX-induced bone loss in rats. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Oil from transgenic Camelina sativa containing over 25 % n-3 long-chain PUFA as the major lipid source in feed for Atlantic salmon (Salmo salar).

PubMed

Betancor, Mónica B; Li, Keshuai; Bucerzan, Valentin S; Sprague, Matthew; Sayanova, Olga; Usher, Sarah; Han, Lihua; Norambuena, Fernando; Torrissen, Ole; Napier, Johnathan A; Tocher, Douglas R; Olsen, Rolf E

2018-06-01

Facing a bottleneck in the growth of aquaculture, and a gap in the supply and demand of the highly beneficial n-3 long-chain PUFA (LC-PUFA), sustainable alternatives to traditional marine-based feeds are required. Therefore, in the present trial, a novel oil obtained from a genetically engineered oilseed crop, Camelina sativa, that supplied over 25 % n-3 LC-PUFA was tested as a sole dietary-added lipid source in Atlantic salmon (Salmo salar) feed. Three groups of fish were fed three experimental diets for 12 weeks with the same basal composition and containing 20 % added oil supplied by either a blend of fish oil and rapeseed oil (1:3) (COM) reflecting current commercial formulations, wild-type Camelina oil (WCO) or the novel transgenic Camelina oil (TCO). There were no negative effects on the growth, survival rate or health of the fish. The whole fish and flesh n-3 LC-PUFA levels were highest in fish fed TCO, with levels more than 2-fold higher compared with those of fish fed the COM and WCO diets, respectively. Diet TCO had no negative impacts on the evaluated immune and physiological parameters of head kidney monocytes. The transcriptomic responses of liver and mid-intestine showed only mild effects on metabolism genes. Overall, the results clearly indicated that the oil from transgenic Camelina was highly efficient in supplying n-3 LC-PUFA providing levels double that obtained with a current commercial standard, and similar to those a decade ago before substantial dietary fishmeal and oil replacement.
Chemistry and biology of ω-3 PUFA peroxidation-derived compounds.

PubMed

Wang, Weicang; Yang, Haixia; Johnson, David; Gensler, Catherine; Decker, Eric; Zhang, Guodong

2017-09-01

The ω-3 polyunsaturated fatty acids (PUFAs) are among the most popular dietary supplements in the US, but they are chemically unstable and highly prone to lipid peroxidation. Many studies performed in different countries demonstrate that the majority of ω-3 PUFA products on the market are oxidized, suggesting that the resulting ω-3 PUFA peroxidation-derived compounds could be widely consumed by the general public. Therefore, it is of practical importance to understand the effects of these oxidized lipid compounds on human health. In this review, we summarize and discuss the chemical structures and biological activities of ω-3 PUFA peroxidation-derived compounds, and emphasize the importance to better understand the role of lipid peroxidation in biological activities of ω-3 PUFAs. Copyright © 2016 Elsevier Inc. All rights reserved.
An Ω-3 fatty acid-deficient diet during gestation induces depressive-like behavior in rats: the role of the hypothalamo-pituitary-adrenal (HPA) system.

PubMed

Tang, Mimi; Liu, Yiping; Wang, Lu; Li, Huande; Cai, Hualin; Zhang, Min; Dang, Ruili; Xue, Ying; Wu, Yanqin

2018-06-08

Low intake of omega-3 (Ω-3) polyunsaturated fatty acids (PUFAs) especially docosahexaenoic acid (DHA) is associated with postpartum depression. DHA deficiency is accompanied by impaired attention and cognition, and will precipitate psychiatric symptoms. However, the effects of dietary DHA on postpartum depression remain unclear. We established a normal pregnancy model to evaluate whether an Ω-3 PUFA-deficient diet during gestation could induce depressive-like behavior and aggravate dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in rats. A between-group design was used to assess the effects of Ω-3 PUFA content (deficiency, control and supplementary) and reproductive status (virgin or parous). We assessed depressive-like behavior and measured the fatty acid composition in the liver. The protein expressions of glucocorticoid receptor (GR) and mineralocorticoid receptor (MCR) were also measured to evaluate the HPA activity. Exposure to the Ω-3 PUFA-deficient diet resulted in an increased immobility time in a forced swimming test (FST). Additionally, our results firstly showed the decreased expression of GR in the hippocampus of parous rats that were exposed to Ω-3 PUFA-deficient diets, which may partly facilitate the hyperactivity of the HPA axis and exert detrimental effects. Moreover, the reduction of GR was ameliorated by Ω-3 PUFA supplementation, providing new evidence for Ω-3 PUFAs in the progression of postpartum depression.
Compared with that of MUFA, a high dietary intake of n-3 PUFA does not reduce the degree of pathology in mdx mice.

PubMed

Henderson, Gregory C; Evans, Nicholas P; Grange, Robert W; Tuazon, Marc A

2014-05-28

Duchenne muscular dystrophy (DMD) is a severe muscle disease that affects afflicted males from a young age, and the mdx mouse is an animal model of this disease. Although new drugs are in development, it is also essential to assess potential dietary therapies that could assist in the management of DMD. In the present study, we compared two diets, high-MUFA diet v. high-PUFA diet, in mdx mice. To generate the high-PUFA diet, a portion of dietary MUFA (oleic acid) was replaced with the dietary essential n-3 PUFA α-linolenic acid (ALA). We sought to determine whether ALA, compared with oleic acid, was beneficial in mdx mice. Consumption of the high-PUFA diet resulted in significantly higher n-3 PUFA content and reduced arachidonic acid content in skeletal muscle phospholipids (PL), while the high-MUFA diet led to higher oleate content in PL. Mdx mice on the high-MUFA diet exhibited 2-fold lower serum creatine kinase activity than those on the high-PUFA diet (P< 0·05) as well as a lower body fat percentage (P< 0·05), but no significant difference in skeletal muscle histopathology results. There was no significant difference between the dietary groups with regard to phosphorylated p65 (an inflammatory marker) in skeletal muscle. In conclusion, alteration of PL fatty acid (FA) composition by the high-PUFA diet made mdx muscle more susceptible to sarcolemmal leakiness, while the high-MUFA diet exhibited a more favourable impact. These results may be important for designing dietary treatments for DMD patients, and future work on dietary FA profiles, such as comparing other FA classes and dose effects, is needed.
Omega-3 deficiency impairs honey bee learning

PubMed Central

Arien, Yael; Dag, Arnon; Zarchin, Shlomi; Masci, Tania

2015-01-01

Deficiency in essential omega-3 polyunsaturated fatty acids (PUFAs), particularly the long-chain form of docosahexaenoic acid (DHA), has been linked to health problems in mammals, including many mental disorders and reduced cognitive performance. Insects have very low long-chain PUFA concentrations, and the effect of omega-3 deficiency on cognition in insects has not been studied. We show a low omega-6:3 ratio of pollen collected by honey bee colonies in heterogenous landscapes and in many hand-collected pollens that we analyzed. We identified Eucalyptus as an important bee-forage plant particularly poor in omega-3 and high in the omega-6:3 ratio. We tested the effect of dietary omega-3 deficiency on olfactory and tactile associative learning of the economically highly valued honey bee. Bees fed either of two omega-3–poor diets, or Eucalyptus pollen, showed greatly reduced learning abilities in conditioned proboscis-extension assays compared with those fed omega-3–rich diets, or omega-3–rich pollen mixture. The effect on performance was not due to reduced sucrose sensitivity. Omega-3 deficiency also led to smaller hypopharyngeal glands. Bee brains contained high omega-3 concentrations, which were only slightly affected by diet, suggesting additional peripheral effects on learning. The shift from a low to high omega-6:3 ratio in the Western human diet is deemed a primary cause of many diseases and reduced mental health. A similar shift seems to be occurring in bee forage, possibly an important factor in colony declines. Our study shows the detrimental effect on cognitive performance of omega-3 deficiency in a nonmammal. PMID:26644556
Comprehensive biometric, biochemical and histopathological assessment of nutrient deficiencies in gilthead sea bream fed semi-purified diets.

PubMed

Ballester-Lozano, Gabriel F; Benedito-Palos, Laura; Estensoro, Itziar; Sitjà-Bobadilla, Ariadna; Kaushik, Sadasivam; Pérez-Sánchez, Jaume

2015-09-14

Seven isoproteic and isolipidic semi-purified diets were formulated to assess specific nutrient deficiencies in sulphur amino acids (SAA), n-3 long-chain PUFA (n-3 LC-PUFA), phospholipids (PL), P, minerals (Min) and vitamins (Vit). The control diet (CTRL) contained these essential nutrients in adequate amounts. Each diet was allocated to triplicate groups of juvenile gilthead sea bream fed to satiety over an 11-week feeding trial period. Weight gain of n-3 LC-PUFA, P-Vit and PL-Min-SAA groups was 50, 60-75 and 80-85 % of the CTRL group, respectively. Fat retention was decreased by all nutrient deficiencies except by the Min diet. Strong effects on N retention were found in n-3 LC-PUFA and P fish. Combined anaemia and increased blood respiratory burst were observed in n-3 LC-PUFA fish. Hypoproteinaemia was found in SAA, n-3 LC-PUFA, PL and Vit fish. Derangements of lipid metabolism were also a common disorder, but the lipodystrophic phenotype of P fish was different from that of other groups. Changes in plasma levels of electrolytes (Ca, phosphate), metabolites (creatinine, choline) and enzyme activities (alkaline phosphatase) were related to specific nutrient deficiencies in PL, P, Min or Vit fish, whereas changes in circulating levels of growth hormone and insulin-like growth factor I primarily reflected the intensity of the nutritional stressor. Histopathological scoring of the liver and intestine segments showed specific nutrient-mediated changes in lipid cell vacuolisation, inflammation of intestinal submucosa, as well as the distribution and number of intestinal goblet and rodlet cells. These results contribute to define the normal range of variation for selected biometric, biochemical, haematological and histochemical markers.
Transgenic expression of omega-3 PUFA synthesis genes improves zebrafish survival during Vibrio vulnificus infection.

PubMed

Cheng, Chih-Lun; Huang, Shin-Jie; Wu, Chih-Lu; Gong, Hong-Yi; Ken, Chuian-Fu; Hu, Shao-Yang; Wu, Jen-Leih

2015-11-17

Highly desaturated n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are synthesized by desaturases and elongase. They exert hepatoprotective effects to prevent alcoholic fatty liver syndrome or cholestatic liver injury. However, it is unclear how n-3 PUFAs improve immune function in liver. Vibrio vulnificus, a gram-negative bacterial pathogen, causes high mortality of aquaculture fishes upon infection. Humans can become infected with V. vulnificus through open wounds or by eating raw seafood, and such infections may result in systemic septicemia. Moreover, patients with liver diseases are vulnerable to infection, and are more likely than healthy persons to present with liver inflammation following infection. This study quantified n-3 PUFAs and their anti-bacterial effects in Fadsd6 and Elvol5a transgenic zebrafish. Two transgenic zebrafish strains with strong liver specific expression of Fadsd6 and Elvol5a (driven by the zebrafish Fabp10 promoter) were established using the Tol2 system. Synthesis of n-3 PUFAs in these strains were increased by 2.5-fold as compared to wild type (Wt) fish. The survival rate in 24 h following challenge with V. vulnificus was 20 % in Wt, but 70 % in the transgenic strains. In addition, the bacteria counts in transgenic fish strains were significantly decreased. The expression levels of pro-inflammatory genes, such as TNF-α, IL-1β, and NF-κB, were suppressed between 9 and 12 h after challenge. This study confirms the anti-bacterial function of n-3 PUFAs in a transgenic zebrafish model. Fadsd6 and Elvol5a transgenic zebrafish are more resistant to V. vulnificus infection, and enhance survival by diminishing the attendant inflammatory response.
Stability of omega-3 LC-PUFA-rich photoautotrophic microalgal oils compared to commercially available omega-3 LC-PUFA oils.

PubMed

Ryckebosch, Eline; Bruneel, Charlotte; Termote-Verhalle, Romina; Lemahieu, Charlotte; Muylaert, Koenraad; Van Durme, Jim; Goiris, Koen; Foubert, Imogen

2013-10-23

Microalgae are the primary producers of omega-3 LC-PUFA, which are known for their health benefits. Their oil may thus be a potential alternative for fish oil. However, oxidative and hydrolytic stability of omega-3 LC-PUFA oils are important parameters. The purpose of this work was therefore to evaluate these parameters in oils from photoautotrophic microalgae (Isochrysis, Phaeodactylum, Nannochloropsis gaditana, and Nannochloropsis sp.) obtained with hexane/isopropanol (HI) and hexane (H) and compare them with commercial omega-3 LC-PUFA oils. When the results of both the primary and secondary oxidation parameters were put together, it was clear that fish, tuna, and heterotrophic microalgae oil are the least oxidatively stable oils, whereas krill oil and the microalgae oils performed better. The microalgal HI oils were shown to be more oxidatively stable than the microalgal H oils. The hydrolytic stability was shown not to be a problem during the storage of any of the oils.

Randomized controlled trial of oral omega-3 PUFA in solar-simulated radiation-induced suppression of human cutaneous immune responses.

PubMed

Pilkington, Suzanne M; Massey, Karen A; Bennett, Susan P; Al-Aasswad, Naser Mi; Roshdy, Khaled; Gibbs, Neil K; Friedmann, Peter S; Nicolaou, Anna; Rhodes, Lesley E

2013-03-01

Skin cancer is a major public health concern, and the majority of cases are caused by solar ultraviolet radiation (UVR) exposure, which suppresses skin immunity. Omega-3 (n-3) PUFAs protect against photoimmunosuppression and skin cancer in mice, but the impact in humans is unknown. We hypothesized that EPA-rich n-3 PUFA would abrogate photoimmunosuppression in humans. Therefore, a nutritional study was performed to assess the effect on UVR suppression of cutaneous cell-mediated immunity (CMI) reflected by nickel contact hypersensitivity (CHS). In a double-blind, randomized controlled study, 79 volunteers (nickel-allergic women, 22-60 y old, with phototype I or II) took 5 g n-3 PUFA-containing lipid (70% EPA plus 10% DHA) or a control lipid daily for 3 mo. After supplementation, nickel was applied to 3 skin sites preexposed on 3 consecutive days to 1.9, 3.8, or 7.6 J/cm(2) of solar-simulated radiation (SSR) and to 3 unexposed control sites. Nickel CHS responses were quantified after 72 h and the percentage of immunosuppression by SSR was calculated. Erythrocyte [red blood cell (RBC)] EPA was measured by using gas chromatography. SSR dose-related suppression of the nickel CHS response was observed in both groups. Photoimmunosuppression appeared less in the n-3 PUFA group than in the control group (not statistically significant [mean difference (95% CI): 6.9% (-2.1%, 15.9%)]). The difference was greatest at 3.8 J/cm(2) SSR [mean difference: 11% (95% CI: 0.5%, 21.4%)]. Postsupplementation RBC EPA was 4-fold higher in the n-3 PUFA group than in the control group (mean difference: 2.69% (95% CI: 2.23%, 3.14%), which confirmed the EPA bioavailability. Oral n-3 PUFAs appear to abrogate photoimmunosuppression in human skin, providing additional support for their chemopreventive role; verification of study findings is required. This trial was registered at clinicaltrials.gov as NCT01032343.
Dietary n-6 PUFA, carbohydrate:protein ratio and change in body weight and waist circumference: a follow-up study.

PubMed

Jakobsen, Marianne U; Madsen, Lise; Dethlefsen, Claus; Due, Karen M; Halkjær, Jytte; Sørensen, Thorkild I A; Kristiansen, Karsten; Overvad, Kim

2015-05-01

To investigate the association between the intake of n-6 PUFA and subsequent change in body weight and waist circumference at different levels of the carbohydrate:protein ratio. Follow-up study with anthropometric measurements at recruitment and on average 5·3 years later. Dietary intake was determined at recruitment by using an FFQ that was designed for the study and validated. We applied linear regression models with 5-year change in weight or waist circumference as outcome and including a two-way interaction term between n-6 PUFA and carbohydrate intakes, lower-order terms, protein intake, long-chain n-3 PUFA intake and other potential confounders. Due to adjustment for intake of protein, levels of carbohydrate indirectly reflect levels of the carbohydrate:protein ratio. Diet, Cancer and Health follow-up study, Denmark. Women and men (n 29 152) aged 55 years. For a high intake of n-6 PUFA (6·9 % of energy) v. a low intake of n-6 PUFA (3·4 % of energy), the difference in 5-year weight change was -189·7 g (95 % CI -636·8, 257·4 g) at a low carbohydrate:protein ratio and -86·7 g (95 % CI -502·9, 329·6 g) at a high carbohydrate:protein ratio; the differences in 5-year waist circumference change were 0·26 cm (95 % CI -0·47, 0·98 cm) and -0·52 cm (95 % CI -1·19, 0·15 cm), respectively. Inclusion of the dietary glycaemic index did not change the results. No consistent associations between the intake of n-6 PUFA and change in body weight or waist circumference at different levels of the carbohydrate:protein ratio were observed.
Increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acid levels in human plasma after a single dose of long-chain omega-3 PUFA.

PubMed

Schuchardt, Jan Philipp; Schneider, Inga; Willenberg, Ina; Yang, Jun; Hammock, Bruce D; Hahn, Andreas; Schebb, Nils Helge

2014-06-01

Several supplementation studies with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) describe an increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acids in blood, while changes in levels of other LC n-3 and n-6 PUFA-derived oxylipins were minor. In order to investigate the kinetics of changes in oxylipin levels in response to LC n-3 PUFA ingestion, we conducted a single dose treatment study with healthy subjects. In the present kinetic study, we compared patterns of hydroxy, epoxy and dihydroxy fatty acids in plasma of 6 healthy men before and after 6, 8, 24, and 48h of fish oil (1008mg EPA and 672mg DHA) ingestion. Levels of EPA- as well as other LC PUFA-derived hydroxy, epoxy and dihydroxy fatty acids were analyzed in plasma by LC-MS. Additionally, levels of these oxylipins were compared with their parent PUFA levels in plasma phospholipids. All EPA-derived oxylipin levels were significantly increased 6h after LC n-3 PUFA ingestion and gradually drop thereafter reaching the baseline levels about 48h after treatment. The relative increase in EPA plasma phospholipid levels highly correlated with the increase of plasma EPA-derived oxylipin levels at different time points. In contrast, plasma levels of arachidonic acid- and DHA-derived oxylipins as well as parent PUFA levels in plasma phospholipids were hardly changed. Our findings demonstrate that a single dose of LC n-3 PUFAs can rapidly induce a shift in the EPA oxylipin profile of healthy subjects within a few hours. Taking the high biological activity of the EPA-derived epoxy fatty acids into account, even short-term treatment with LC n-3 PUFAs may cause systemic effects, which warrant further investigation. Copyright © 2014 Elsevier Inc. All rights reserved.
Does perinatal omega-3 polyunsaturated fatty acid deficiency increase appetite signaling?

PubMed

Mathai, Michael L; Soueid, Mona; Chen, Nora; Jayasooriya, Anura P; Sinclair, Andrew J; Wlodek, Mary E; Weisinger, Harrison S; Weisinger, Richard S

2004-11-01

To investigate the effect of maternal dietary omega-3 polyunsaturated fatty acid (PUFA) deficiency and repletion on food appetite signaling. Sprague-Dawley rat dams were maintained on diets either supplemented with (CON) or deficient in (DEF) omega-3 PUFA. All offspring were raised on the maternal diet until weaning. After weaning, two groups remained on the respective maternal diet (CON and DEF groups), whereas a third group, born of dams fed the DEF diet, were switched to the CON diet (REC). Experiments on food intake began when the male rats reached 16 weeks of age. Food intake was stimulated either by a period of food restriction, by blocking glucose utilization (by 2-deoxyglucose injection), or by blocking beta-oxidation of fatty acids (by beta-mercaptoacetate injection). DEF animals consumed more than CON animals in response to all stimuli, with the greatest difference (1.9-fold) demonstrated following administration of 2-deoxyglucose. REC animals also consumed more than CON animals in response to food restriction and 2-deoxyglucose but not to beta-mercaptoacetate. These findings indicate that supply of omega-3 PUFA, particularly during the perinatal period, plays a role in the normal development of mechanisms controlling food intake, especially glucoprivic (i.e. reduced glucose availability) appetite signaling. Dietary repletion of omega-3 PUFA from 3 weeks of age restored intake responses to fatty acid metabolite signaling but did not reverse those in response to food restriction or glucoprivic stimuli.
White Bass (Morone chrysops) Preferentially Retain n-3 PUFA in Ova When Fed Prepared Diets with Varying FA Content.

PubMed

Fuller, S Adam; Rawles, Steven D; McEntire, Matthew E; Bader, Troy J; Riche, Marty; Beck, Benjamin H; Webster, Carl D

2017-10-01

We evaluated the fatty acid (FA) composition of broodstock white bass ova fed one of six commercial diets with increasing polyunsaturated FA content (n-6/n-3 ratio; 0.36, 0.39, 0.46, 0.83, 1.07, 1.12) eight weeks prior to sampling. Fatty acid profiles of ova from brooders fed each of the six diets were significantly altered according to canonical discriminant analysis. Ova FA profiles resulting from the 0.39 diet separated those from the 0.36 diet based on lower 18:2n-6 (LNA) and higher 20:1n-9 concentrations from the 0.36 diet. Ova profiles were further separated based on lower concentrations of 22:5n-3 (DPA) from the 0.46 diet, lower concentrations of 20:5n-3 (EPA) in the 1.12 and 0.83 diets, and lower concentrations of 22:6n-3 (DHA) in all other diets relative to the 0.46 diet. Changes in ova FA profile at four and eight weeks were consistent with dietary intake with an approximate 2% increase in any given FA class with increasing time on individual diet. There was no correlation between dietary ARA concentrations (0.7-1.1 mol%), or dietary EPA/ARA ratios (7-15), and the concentrations (1.4-1.7 mol%) or ratios (3.3-4.4) found in the ova by diet. Our results suggest that white bass females have the ability to preferentially incorporate n-3 PUFA, particularly DHA, suggesting mobilization of this FA from other tissues for ova deposition or preferential dietary incorporation of PUFA into ova. These results will add to the limited FA information available in white bass and enable nutritionists to formulate broodstock diets that maximize reproductive potential in this species.
Plasma n-3 and n-6 fatty acids and inflammatory markers in Chinese vegetarians.

PubMed

Yu, Xiaomei; Huang, Tao; Weng, Xiumei; Shou, Tianxing; Wang, Qiang; Zhou, Xiaoqiong; Hu, Qinxin; Li, Duo

2014-09-29

Polyunsaturated fatty acid (PUFA) intake favorably affects chronic inflammatory-related diseases such as cardiovascular disease; however, the relationship between the PUFA and inflammatory factors in the healthy vegetarians were not clear. We aimed to investigate the plasma fatty acids status, and its association with plasma inflammatory factors in Chinese vegetarians and omnivores. A total of 89 male vegetarians and 106 male omnivores were participated the study. Plasma concentrations of inflammatory factors were detected by ELISA, and as standard methods fatty acids were extracted and determined by chromatography. Compared with omnivores, vegetarians have significant higher interleukin-6 (IL-6), plasma n-6 PUFA, n-6/n-3, and 18:3n-3; while they have significant lower leukotriene B4 (LTB4), cyclo-oxygenase-2 (COX2) and prostaglandin E2 (PGE2), 20:5n-3, 22:5n-3, 22:6n-3, and n-3 PUFA. In vegetarians, plasma 20:4n-6 was significant positively related to TNF-α. LTB4 was significantly positively related to plasma 22:6n-3, and negatively associated with n-6 PUFA. Vegetarians have higher plasma n-6 PUFA and IL-6, but lower LTB4, n-3 PUFA, 22:6n-3, COX2 and PGE2 levels. It would seem appropriate for vegetarians to increase their dietary n-3 PUFA, while reduce dietary n-6 PUFA and thus reduce the risk of chronic inflammatory-related diseases.
Maternal PUFA omega-3 supplementation prevents hyperoxia-induced pulmonary hypertension in the offspring.

PubMed

Zhong, Ying; Catheline, Daniel; Houeijeh, Ali; Sharma, Dyuti; Du, Li-Zhong; Besengez, Capucine; Deruelle, Philippe; Legrand, Philippe; Storme, Laurent

2018-03-29

Pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) affect 16-25% of premature infants with bronchopulmonary dysplasia (BPD), contributing significantly to perinatal morbidity and mortality. Polyunsaturated fatty acids ω-3 (PUFA ω-3) can improve vascular remodeling, angiogenesis, and inflammation under pathophysiological conditions. However, the effects of PUFA ω-3 supplementation in BPD-associated PH are unknown. The present study aimed to evaluate the effects of PUFA ω-3 on pulmonary vascular remodeling, angiogenesis, and inflammatory response in a hyperoxia-induced rat model of PH. From embryonic day 15, pregnant Spague-Dawley rats were supplemented daily with PUFA ω-3, PUFA ω-6, or normal saline (0.2 ml/day). After birth, pups were pooled, assigned as 12 per litter, and randomly to either in air or continuous oxygen exposure (FiO2 = 85%) for 20 days, then sacrificed for pulmonary hemodynamic and morphometric analysis. We found that PUFA ω-3 supplementation improved survival, decreased right ventricular systolic pressure and RVH caused by hyperoxia, and significantly improved alveolarization, vascular remodeling, and vascular density. PUFA ω-3 supplementation produced a higher level of total ω-3 in lung tissue and breast milk, and was found reversing the reduced levels of VEGFA, VEGFR-2, ANGPT-1, TIE-2, eNOS, and NO concentrations in lung tissue, and the increased ANGPT-2 levels in hyperoxia-exposed rats. The beneficial effects of PUFA ω-3 in improving lung injuries were also associated with an inhibition of leukocyte infiltration, and reduced expression of proinflammatory cytokines IL-1β, IL-6 and TNF-α. These data indicated that maternal PUFA ω-3 supplementation strategies could effectively protect against infant PH induced by hyperoxia.
Protective Effects of ω-3 PUFA in Anthracycline-Induced Cardiotoxicity: A Critical Review.

PubMed

Serini, Simona; Ottes Vasconcelos, Renata; Nascimento Gomes, Renata; Calviello, Gabriella

2017-12-12

It has been demonstrated that ω-3 polyunsaturated fatty acids (ω-3 PUFA) may exert a beneficial role as adjuvants in the prevention and treatment of many disorders, including cardiovascular diseases and cancer. Particularly, several in vitro and in vivo preclinical studies have shown the antitumor activity of ω-3 PUFA in different kinds of cancers, and several human studies have shown that ω-3 PUFA are able to decrease the risk of a series of cardiovascular diseases. Several mechanisms have been proposed to explain their pleiotropic beneficial effects. ω-3 PUFA have also been shown to prevent harmful side-effects (including cardiotoxicity and heart failure) induced by conventional and innovative anti-cancer drugs in both animals and patients. The available literature regarding the possible protective effects of ω-3 PUFA against anthracycline-induced cardiotoxicity, as well as the mechanisms involved, will be critically discussed herein. The study will analyze the critical role of different levels of ω-3 PUFA intake in determining the results of the combinatory studies with anthracyclines. Suggestions for future research will also be considered.
Long-chain n-3 PUFA supplementation decreases physical activity during class time in iron-deficient South African school children.

PubMed

Smuts, Cornelius M; Greeff, Jani; Kvalsvig, Jane; Zimmermann, Michael B; Baumgartner, Jeannine

2015-01-28

Both Fe deficiency and poor n-3 fatty acid status have been associated with behavioural changes in children. In the present study, we investigated the effects of Fe and DHA+EPA supplementation, alone or in combination, on physical activity during school days and on teacher-rated behaviour in healthy Fe-deficient school children. In a 2 × 2 factorial design, children (n 98, 6-11 years) were randomly assigned to receive (1) Fe (50 mg) plus DHA (420 mg)+EPA (80 mg), (2) Fe plus placebo, (3) placebo plus DHA+EPA or (4) placebo plus placebo as oral supplements (4 d/week) for 8.5 months. Physical activity was measured during four school days at baseline and endpoint using accelerometers, and data were stratified into morning class time (08.00-10.29 hours), break time (10.30-11.00 hours) and after-break class time (11.01-12.00 hours) for analysis. Classroom behaviour was assessed at endpoint using Conners' Teacher Rating Scales. DHA+EPA supplementation decreased physical activity counts during morning class time, increased sedentary physical activity, and decreased light- and moderate-intensity physical activities. Consistently, DHA+EPA supplementation increased sedentary physical activity and decreased light-intensity physical activity during after-break class time. Even though there were no treatment effects found on teacher-rated behaviour, lower physical activity during morning class time was associated with lower levels of teacher-rated hyperactivity and oppositional behaviour at endpoint. Despite a positive association between Fe status and physical activity during break time at baseline, Fe supplementation did not affect physical activity during break time and class time. Our findings suggest that DHA+EPA supplementation may decrease physical activity levels during class time, and further indicate that accelerometry might be a useful tool to assess classroom behaviour in healthy children.
Relationship between diet and plasma long-chain n-3 PUFAs in older people: impact of apolipoprotein E genotype

PubMed Central

Samieri, Cécilia; Lorrain, Simon; Buaud, Benjamin; Vaysse, Carole; Berr, Claudine; Peuchant, Evelyne; Cunnane, Stephen C.; Barberger-Gateau, Pascale

2013-01-01

The main risk factors for Alzheimer's disease, age and the ϵ4 allele of the APOE gene (APOE4), might modify the metabolism of n-3 PUFAs and in turn, their impact on cognition. The aim of this study was to investigate the association between dietary fat and plasma concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in elderly persons, taking the APOE4 genotype into account. The sample was composed of 1,135 participants from the Three-City study aged 65 years and over, of whom 19% were APOE4 carriers. Mean plasma proportions of EPA [1.01%, standard deviation (SD) 0.60] and DHA (2.41%, SD 0.81) did not differ according to APOE4. In multivariate models, plasma EPA increased with frequency of fish consumption (P < 0.0001), alcohol intake (P = 0.0006), and female gender (P = 0.02), and decreased with intensive consumption of n-6 oils (P = 0.02). The positive association between fish consumption and plasma DHA was highly significant whatever the APOE genotype (P < 0.0001) but stronger in APOE4 noncarriers than in carriers (P = 0.06 for interaction). Plasma DHA increased significantly with age (P = 0.009) in APOE4 noncarriers only. These findings suggest that dietary habits, gender, and APOE4 genotype should be considered when designing interventions to increase n-3 PUFA blood levels in older people. PMID:23801662
Genetic variant modifies the effect of N3 PUFAs on DNA methylation of IL6 in the Genetics of Lipid Lowering Drugs and Diet Network study

USDA-ARS?s Scientific Manuscript database

N3 polyunsaturated fatty acids (N3 PUFAs) ameliorate inflammation status with specific regulation on interleukin-6 (IL6) expression. However, the molecular mechanism for this regulation is unclear. Using both cell lines data from Encyclopedia of DNA Elements (ENCODE) consortium and population data f...
Glucokinase Regulatory Protein Genetic Variant Interacts with Omega-3 PUFA to Influence Insulin Resistance and Inflammation in Metabolic Syndrome

PubMed Central

Garcia-Rios, Antonio; Mc Monagle, Jolene; Gulseth, Hanne L.; Ordovas, Jose M.; Shaw, Danielle I.; Karlström, Brita; Kiec-Wilk, Beata; Blaak, Ellen E.; Helal, Olfa; Malczewska-Malec, Małgorzata; Defoort, Catherine; Risérus, Ulf; Saris, Wim H. M.; Lovegrove, Julie A.; Drevon, Christian A.; Roche, Helen M.; Lopez-Miranda, Jose

2011-01-01

Glucokinase Regulatory Protein (GCKR) plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS) risk. Objective To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP) and n-3 PUFA in MetS subjects. Design Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort. Results Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019), C-peptide (P = 0.004), HOMA-IR (P = 0.008) and CRP (P = 0.032) as compared with subjects carrying the minor T-allele (Leu446). In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele. Conclusions We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals. Trial Registration ClinicalTrials.gov NCT00429195 PMID:21674002
Uncoupling of interleukin-6 from its signalling pathway by dietary n-3-polyunsaturated fatty acid deprivation alters sickness behaviour in mice

PubMed Central

Mingam, Rozenn; Moranis, Aurélie; Bluthé, Rose-Marie; De Smedt-Peyrusse, Véronique; Kelley, Keith W.; Guesnet, Philippe; Lavialle, Monique; Dantzer, Robert; Layé, Sophie

2009-01-01

Sickness behaviour is an adaptive behavioural response to the activation of the innate immune system. It is mediated by brain cytokine production and action, especially interleukin-6 (IL-6). Polyunsaturated fatty acids (PUFA) are essential fatty acids that are highly incorporated in brain cells membranes and display immunomodulating properties. We hypothesized that a decrease in n-3 PUFA brain level by dietary means impacts on lipopolysaccharide (LPS)-induced IL-6 production and sickness behaviour. Our results show that mice exposed throughout life to a diet containing n-3 PUFA (n-3/n-6 diet) display a decrease in social interaction that does not occur in mice submitted to a diet devoid of n-3 PUFA (n-6 diet). LPS induced high IL-6 plasma levels as well as expression of IL-6 mRNA in the hippocampus and cFos mRNA in the brainstem of mice fed either diet, indicating intact immune-to-brain communication. However, STAT3 and STAT1 activation, a hallmark of IL-6 signalling pathway, was lower in the hippocampus of LPS-treated n-6 mice as compared to n-3/n-6 mice. In addition, LPS did not reduce social interaction in IL-6 knock-out (IL-6 KO) mice and failed to induce STAT3 activation in the brain of IL-6 KO mice. Altogether, these findings point to alteration in brain STAT3 as a key mechanism for the lack of effect of LPS on social interaction in mice fed with the n-6 PUFA diet. The relative deficiency of Western diets in n-3 PUFA could impact on behavioural aspects of the host response to infection. PMID:18973601
[Enrichment effect of vitamin-deficient diet of rats by polyunsaturated fatty acids omega-3 on vitamin biomarkers and antioxidant status].

PubMed

Vrzhesinskaia, O A; Beketova, V M; Kodentsova, O G; Pereverzeva, O G; Kosheleva, O V; Sokol'nikov, A A; Kulakova, S N; Baturina, V A; Soto, S Kh

2013-01-01

Using the model of combined vitamin deficiency based on 5-fold reduction of the amount of vitamin mixture in semi-synthetic diet and on vitamin E exclusion from the mixture, the influence of omega-3 polyunsaturated fatty acids (PUFA) on vitamin and antioxidant status has been investigated. The enrichment of rat diet with PUFA was achieved by replacing of sunflower oil (4.5% of the diet) on linseed oil. This substitute led to omega-3 PUFA elevation from 0.03 to 2.4 g per 100 g of food and PUFA and saturated fatty acids diet ratio increased from 1.3 to 1.9. The diet treatment with PUFA did not affect blood plasma retinol concentration and total vitamin A (retinol palmitate and retinol) rat liver content, while liver retinol significantly 1,5-fold elevated. Despite of preliminary equation of tocopherols content in vegetable oils (up to 60 IU per 100 g by adding dl-alpha-tocopherol to linseed oil) the consuming of linen oil deteriorated animal vitamin E supply. The liver alpha-tocopherol content significantly decreased by 14%, its blood plasma concentration insignificantly decreased by 26%, while the amount of beta - and gamma-tocopherol significantly increased in 5,4-fold. At the same deprivation of vitamin D in the diet of rats treated with linseed oil 25(OH)D blood plasma concentration was 1,3-fold higher compared with the animals treated with sunflower oil, but the difference did not reach significance reliable. In this case, this index had significant differences from that of the receiving adequate diet rats in control group, having 2-fold higher concentration of vitamin D transport form in blood plasma. PUFA enrichment of the combined vitamin-deficit diet did not affect liver level of vitamin C, vitamin B1 and vitamin B2. Contrary to the assumptions, the enrichment with PUFA of vitamin-deficient diet did not lead to a further increase of liver MDA level and a decrease of liver ascorbic acid content, which is typical for animals in combined vitamin deficiency. The
Heterologous expression of C. elegans fat-1 decreases the n-6/n-3 fatty acid ratio and inhibits adipogenesis in 3T3-L1 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

An, Lei, E-mail: anleim@yahoo.com.cn; Pang, Yun-Wei, E-mail: yunweipang@126.com; Gao, Hong-Mei, E-mail: Gaohongmei_123@yahoo.cn

Highlights: Black-Right-Pointing-Pointer Expression of C. elegans fat-1 reduces the n-6/n-3 PUFA ratio in 3T3-L1 cells. Black-Right-Pointing-Pointer fat-1 inhibits the proliferation and differentiation of 3T3-L1 preadipocytes. Black-Right-Pointing-Pointer fat-1 reduces lipid deposition in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer The lower n-6/n-3 ratio induces apoptosis in 3T3-L1 adipocytes. -- Abstract: In general, a diet enriched in polyunsaturated fatty acids (PUFAs) inhibits the development of obesity and decreases adipose tissue. The specific impacts of n-3 and n-6 PUFAs on adipogenesis, however, have not been definitively determined. Traditional in vivo and in vitro supplementation studies have yielded inconsistent or even contradictory results, which likely reflect insufficiently controlledmore » experimental systems. Caenorhabditiselegans fat-1 gene encodes an n-3 fatty acid desaturase, and its heterologous expression represents an effective method both for altering the n-6/n-3 PUFA ratio and for evaluating the biological effects of n-3 and n-6 PUFAs. We sought to determine whether a reduced n-6/n-3 ratio could influence adipogenesis in 3T3-L1 cells. Lentivirus-mediated introduction of the fat-1 gene into 3T3-L1 preadipocytes significantly reduced the n-6/n-3 ratio and inhibited preadipocyte proliferation and differentiation. In mature adipocytes, fat-1 expression reduced lipid deposition, as measured by Oil Red O staining, and induced apoptosis. Our results indicate that a reduced n-6/n-3 ratio inhibits adipogenesis through several mechanisms and that n-3 PUFAs more effectively inhibit adipogenesis (but not lipogenesis) than do n-6 PUFAs.« less
Decreased n-6/n-3 polyunsaturated fatty acid ratio reduces chronic reflux esophagitis in rats.

PubMed

Wei, Jing-Jing; Tang, Du-Peng; Xie, Jing-Jing; Yang, Li-Yong; Zhuang, Ze-Hao

2016-09-01

To investigate the effect of dietary ratio of n-6/n-3 PUFAs on chronic reflux esophagitis (RE) and lipid peroxidation. Rat RE model were established and then fed on a diet contained different n-6/n-3 PUFA ratios (1:1.5, 5:1, 10:1) or received pure n-6 PUFA diet for 14 days. Esophageal pathological changes were evaluated using macroscopic examination and hematoxyline-eosin staining. IL-1β, IL-8, and TNFα mRNA and protein levels of were determined using RT-PCR and Western blotting, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined using ELISA. The severity of esophagitis was lowest in the PUFA(1:1.5) group (P<0.05). IL-1β, IL-8, and TNFα mRNA and protein and MDA levels were significantly increased in model groups with the increasing n-6/n-3 PUFA ratios. SOD levels were significantly decreased in all RE PUFA groups (P<0.05). Esophageal injury and lipid peroxidation appeared to be ameliorated by increased n-3 PUFAs intake. Copyright © 2016 Elsevier Ltd. All rights reserved.
Feeding soy protein isolate and n-3 PUFA affects polycystic liver disease progression in a PCK rat model of autosomal polycystic kidney disease.

PubMed

Maditz, Kaitlin H; Benedito, Vagner A; Oldaker, Chris; Nanda, Nainika; Lateef, Sundus S; Livengood, Ryan; Tou, Janet C

2015-04-01

In polycystic liver disease (PCLD), multiple cysts cause liver enlargement, structural damage, and loss of function. Soy protein and dietary ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been found to decrease cyst proliferation and inflammation in polycystic kidney disease. Therefore, the aim of the study was to investigate whether soy protein and n-3 PUFA supplementation attenuates PCLD. Young (age 28 days) female PCK rats were fed (n = 12 per group) either casein + corn oil (casein + CO), casein + soybean oil (casein + SO), soy protein isolate + soybean oil (SPI + SO), or SPI + 1:1 soybean/salmon oil blend (SPI + SB) diet for 12 weeks. Liver histology, gene expression by real-time quantitative polymerase chain reaction, and serum markers of liver injury were determined. Diet had no effect on PCLD progression as indicated by no significant differences in liver weight and hepatic proliferation gene expression between diet groups. PCK rats fed SPI + SB diet, however, had the greatest (P < 0.05) histological evidence of hepatic cyst obstruction, portal inflammation, steatosis, and upregulation (P = 0.03) of fibrosis-related genes. Rats fed SPI + SB diet also had the lowest (P < 0.001) serum cholesterol and higher (P < 0.05) serum alkaline phosphatase and bilirubin concentrations. Feeding young female PCK rats SPI and n-3 PUFA failed to attenuate PCLD progression. Furthermore, feeding SPI + SB diet resulted in complications of hepatic steatosis attributable to cysts obstruction of bile duct and hepatic vein. Based on the results, it was concluded that diet intervention alone was not effective at attenuating PCLD associated with autosomal recessive polycystic kidney disease.
Survey of n-3 and n-6 polyunsaturated fatty acids in fish and fish products

PubMed Central

2012-01-01

Background The imbalance of the n-3/n-6 ratio in the Western diet is characterised by a low intake of n-3 long-chain (LC) PUFA and a concurrent high intake of n-6 PUFA. Fish, in particular marine fish, is a unique source of n-3 LC PUFA. However, FA composition of consumed fish changed, due to the increasing usage of n-6 PUFA-rich vegetable oils in aquaculture feed and in fish processing (frying) which both lead to a further shift in n-6 PUFA to the detriment of n-3 LC PUFA. The aim of this study was to determine the ratio of n-3/n-6 including the contents of EPA and DHA in fish fillets and fish products from the German market (n=123). Furthermore, the study focussed on the FA content in farmed salmon compared to wild salmon as well as in processed Alaska pollock fillet, e.g., fish fingers. Results Total fat and FA content in fish products varied considerably depending on fish species, feed management, and food processing. Mackerel, herring and trout fillets characteristically contained adequate dietary amounts of absolute EPA and DHA, due to their high fat contents. However, despite a lower fat content, tuna, pollock, and Alaska pollock can contribute considerable amounts of EPA and DHA to the human supply. Farmed salmon are an appropriate source of EPA and DHA owing to their higher fat content compared to wild salmon (12.3 vs. 2.1 wt %), however with elevated SFA, n-9 and n-6 FA contents representing the use of vegetable oils and oilseeds in aquaculture feed. The n-3/n-6 ratio was deteriorated (2.9 vs. 12.4) but still acceptable. Compared to pure fish fillets, breaded and pre-fried Alaska pollock fillet contained extraordinarily high fat and n-6 PUFA levels. Conclusions Since fish species vary with respect to their n-3 LC PUFA contents, eating a variety of fish is advisable. High n-6 PUFA containing pre-fried fish support the imbalance of n-3/n-6 ratio in the Western diet. Thus, consumption of pure fish fillets is to be favoured. The lower n-3 PUFA portion in
Survey of n-3 and n-6 polyunsaturated fatty acids in fish and fish products.

PubMed

Strobel, Claudia; Jahreis, Gerhard; Kuhnt, Katrin

2012-10-30

The imbalance of the n-3/n-6 ratio in the Western diet is characterised by a low intake of n-3 long-chain (LC) PUFA and a concurrent high intake of n-6 PUFA. Fish, in particular marine fish, is a unique source of n-3 LC PUFA. However, FA composition of consumed fish changed, due to the increasing usage of n-6 PUFA-rich vegetable oils in aquaculture feed and in fish processing (frying) which both lead to a further shift in n-6 PUFA to the detriment of n-3 LC PUFA.The aim of this study was to determine the ratio of n-3/n-6 including the contents of EPA and DHA in fish fillets and fish products from the German market (n=123). Furthermore, the study focussed on the FA content in farmed salmon compared to wild salmon as well as in processed Alaska pollock fillet, e.g., fish fingers. Total fat and FA content in fish products varied considerably depending on fish species, feed management, and food processing. Mackerel, herring and trout fillets characteristically contained adequate dietary amounts of absolute EPA and DHA, due to their high fat contents. However, despite a lower fat content, tuna, pollock, and Alaska pollock can contribute considerable amounts of EPA and DHA to the human supply.Farmed salmon are an appropriate source of EPA and DHA owing to their higher fat content compared to wild salmon (12.3 vs. 2.1 wt %), however with elevated SFA, n-9 and n-6 FA contents representing the use of vegetable oils and oilseeds in aquaculture feed. The n-3/n-6 ratio was deteriorated (2.9 vs. 12.4) but still acceptable. Compared to pure fish fillets, breaded and pre-fried Alaska pollock fillet contained extraordinarily high fat and n-6 PUFA levels. Since fish species vary with respect to their n-3 LC PUFA contents, eating a variety of fish is advisable. High n-6 PUFA containing pre-fried fish support the imbalance of n-3/n-6 ratio in the Western diet. Thus, consumption of pure fish fillets is to be favoured. The lower n-3 PUFA portion in farmed fish can be offset by the
Effects of n-3 long-chain PUFA supplementation to lactating mothers and their breastfed children on child growth and morbidity: a 2 × 2 factorial randomized controlled trial in rural Ethiopia.

PubMed

Argaw, Alemayehu; Wondafrash, Mekitie; Bouckaert, Kimberley P; Kolsteren, Patrick; Lachat, Carl; Belachew, Tefera; De Meulenaer, Bruno; Huybregts, Lieven

2018-03-01

Recurrent infections and inflammation contribute to growth faltering in low-income countries. n-3 (ω-3) Long-chain polyunsaturated fatty-acids (LC-PUFAs) may improve immune maturation, resistance to infections, and growth in young children who are at risk. We evaluated the independent and combined effects of fish oil (500 mg n-3 LC-PUFAs/d) supplementation to lactating mothers and their breastfed children, aged 6-24 mo, on child morbidity, systemic inflammation, and growth in southwest Ethiopia. A 4-arm double-blind randomized controlled trial was conducted by enrolling 360 mother-infant pairs with infants 6-12 mo old. Study arms were both the lactating mother and child receiving fish oil intervention (MCI), only the lactating mother receiving fish oil intervention and child receiving placebo control (MI), only the child receiving intervention and mother receiving placebo control (CI), and both mother and child receiving a placebo supplement or control (C). The primary study outcome was linear growth using monthly changes in length-for-age z score. Anthropometric measurements were taken monthly, and hemoglobin, C-reactive protein, and blood LC-PUFAs were measured at baseline and after 6 and 12 mo of follow-up. Weekly morbidity surveillance was conducted throughout the study. Fish-oil supplementation significantly increased blood n-3 LC-PUFA concentration (P < 0.01) and decreased the arachidonic acid:(docosahexaenoic acid + eicosapentaenoic acid) ratio (P < 0.001) in all intervention arms. No significant intervention effect was found on linear growth, morbidity, or systemic inflammation. Compared to the control group, a small positive effect on monthly changes in weight-for-length z scores was found in the CI arm (effect size: 0.022/mo; 95% CI: 0.005, 0.039/mo; P = 0.012) and the MCI arm (effect size: 0.018/mo; 95% CI: 0.001, 0.034/mo; P = 0.041). n-3 LC-PUFA supplementation of lactating mothers and children did not affect child linear growth and

n-3 Polyunsaturated fatty acids in animal models with neuroinflammation.

PubMed

Orr, Sarah K; Trépanier, Marc-Olivier; Bazinet, Richard P

2013-01-01

Neuroinflammation is present in the majority of acute and chronic neurological disorders. Excess or prolonged inflammation in the brain is thought to exacerbate neuronal damage and loss. Identifying modulators of neuroinflammation is an active area of study since it may lead to novel therapies. Omega-3 polyunsaturated fatty acids (n-3 PUFA) are anti-inflammatory in many non-neural tissues; their role in neuroinflammation is less studied. This review summarizes the relationship between n-3 PUFA and brain inflammation in animal models of brain injury and aging. Evidence by and large shows protective effects of n-3 PUFA in models of sickness behavior, stroke, aging, depression, Parkinson's disease, diabetes, and cytokine- and irradiation-induced cognitive impairments. However, rigorous studies that test the direct effects of n-3 PUFA in neuroinflammation in vivo are lacking. Future research in this area is necessary to determine if, and if so which, n-3 PUFA directly target brain inflammatory pathways. n-3 PUFA bioactive metabolites may provide novel therapeutic targets for neurological disorders with a neuroinflammatory component. Copyright © 2012 Elsevier Ltd. All rights reserved.
Effect of PUFA on patients with hypertension: A hospital based study

PubMed Central

Shantakumari, Nisha; Eldeeb, Rasha Ali; Mabrouk Ibrahim, Salwa Abdelzaher; Sreedharan, Jayadevan; Otoum, Sufian

2014-01-01

Introduction Hypertension affects more than a quarter of the global adult population. Studies conducted worldwide suggest an overall small, yet useful, role of omega-3 PUFAs in reducing blood pressure in hypertensive patients. However there is no substantial data in this regard from population based in Middle East and Asia. Objectives To determine the effects of (omega-3) PUFA supplementation on the blood pressure of hypertensive patient. To identify if male and female hypertensive patients respond differently to PUFA. To identify if response of hypertensive patients to PUFA varies with the duration of hypertension and co-existence of diabetes/dyslipidemia. Materials and methods This observational study was conducted among hypertensive patients visiting OPD of the Gulf Medical College Hospital, Ajman, UAE, during the period Jan–Dec 2012. A total of 100 hypertensive patients on treatment with their antihypertensive medications, 50 of whom were taking n-3 PUFA supplementation, were followed up for a period of 3 months. Comparisons were drawn between the BP recordings at the time of enrollment in the study and their follow up values 3 months after enrollment. Results There was a statistically significant reduction in both the systolic and diastolic blood pressures after 3 months of PUFA therapy. The BP lowering effect of PUFA was more in males. A statistically significant reduction in BP was noted in non-diabetic patients and patients with long standing hypertension. Conclusion Findings of the study suggest that omega-3 PUFA dietary supplements augment the benefits of pharmacotherapy in hypertension. PMID:25173198
Ratio of Dietary n-6/n-3 Polyunsaturated Fatty Acids Independently Related to Muscle Mass Decline in Hemodialysis Patients.

PubMed

Wong, Te-Chih; Chen, Yu-Tong; Wu, Pei-Yu; Chen, Tzen-Wen; Chen, Hsi-Hsien; Chen, Tso-Hsiao; Yang, Shwu-Huey

2015-01-01

n-3 polyunsaturated fatty acids (PUFAs) might be useful nutritional strategy for treating patients with sarcopenia. We evaluated the effect of the intake of dietary n-3 PUFAs on the skeletal muscle mass (SMM), appendicular skeletal muscle mass (ASM), and its determinants in patients receiving standard hemodialysis (HD) treatment for the management of end stage renal disease. In this cross-sectional study, data of 111 HD patients were analyzed. Anthropometric and bioelectrical impedance measurements used to estimate the muscle mass were performed the day of dialysis immediately after the dialysis session. Routine laboratory and 3-day dietary data were also collected. The cutoff value of adequate intake (AI) for both n-3 PUFAs and alpha-linolenic acid (ALA) was 1.6 g/day and 1.1 g/day for men and women, respectively. The mean age, mean dietary n-3 PUFAs intake, ALA intake, ratio of n-6/n-3 PUFAs intake, SMM, and ASM of patients were 61.4 ± 10.4 years, 2.0 ± 1.3 g/day, 1.5 ± 1.0 g/day, 9.5 ± 6.7 g/day, 23.9 ± 5.5 kg, and 17.5 ± 4.5 kg, respectively. A higher SMM and ASM significantly observed in patients who achieved an AI of n-3 PUFAs. Similar trends appeared to be observed among those patients who achieved the AI of ALA, but the difference was not significantly, except for ASM (P = 0.047). No relevant differences in demographics, laboratory and nutritional parameters were observed, regardless of whether the patients achieved an AI of n-3 PUFAs. Multivariate analysis showed that the BMI and equilibrated Kt/V were independent determinants of the muscle mass. Moreover, the ratio of n-6/n-3 PUFAs was an independent risk determinant of reduced ASM in HD patients. Patients with an AI of n-3 PUFAs had better total-body SMM and ASM. A higher dietary ratio of n-6/n-3 PUFAs seemed to be associated with a reduced muscle mass in HD patients.
Fish oil LC-PUFAs do not affect blood coagulation parameters and bleeding manifestations: Analysis of 8 clinical studies with selected patient groups on omega-3-enriched medical nutrition.

PubMed

Jeansen, Stephanie; Witkamp, Renger F; Garthoff, Jossie A; van Helvoort, Ardy; Calder, Philip C

2018-06-01

The increased consumption of fish oil enriched-products exposes a wide diversity of people, including elderly and those with impaired health to relatively high amounts of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs). There is an ongoing debate around the possible adverse effects of n-3 LC-PUFAs on bleeding risk, particularly relevant in people with a medical history of cardiovascular events or using antithrombotic drugs. This analysis of 8 clinical intervention studies conducted with enteral medical nutrition products containing fish oil as a source of n-3 LC-PUFAs addresses the occurrence of bleeding-related adverse events and effects on key coagulation parameters (Prothrombin Time [PT], (activated) and Partial Thromboplastin Time [(a)PTT]). In all the patients considered (over 600 subjects treated with the active product in total), with moderate to severe disease, with or without concomitant use of antithrombotic agents, at home or in an Intensive Care Unit (ICU), no evidence of increased risk of bleeding with use of n-3 LC-PUFAs was observed. Furthermore there were no statistically significant changes from baseline in measured coagulation parameters. These findings further support the safe consumption of n-3 LC-PUFAs, even at short-term doses up to 10 g/day of eicosapentaenoic acid + docosahexaenoic acid (EPA + DHA) or consumed for up to 52 weeks above 1.5 g/day, in selected vulnerable and sensitive populations such as subjects with gastrointestinal cancer or patients in an ICU. We found no evidence to support any concern raised with regards to the application of n-3 LC-PUFAs and the potentially increased risk for the occurrence of adverse bleeding manifestations in these selected patient populations consuming fish oil enriched medical nutrition. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Combined deficiency of iron and (n-3) fatty acids in male rats disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone.

PubMed

Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

2012-08-01

Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed an ID, (n-3)FAD, ID+(n-3)FAD, or control diet for 5 wk postweaning (postnatal d 21-56) after (n-3)FAD had been induced over 2 generations. The (n-3)FAD and ID diets decreased brain (n-3) FA by 70-76% and Fe by 20-32%, respectively. ID and (n-3)FAD significantly increased dopamine (DA) concentrations in the olfactory bulb (OB) and striatum, with an additive 1- to 2-fold increase in ID+(n-3)FAD rats compared with controls (P < 0.05). ID decreased serotonin (5-HT) levels in OB, with a significant decrease in ID+(n-3)FAD rats. Furthermore, norepinephrine concentrations were increased 2-fold in the frontal cortex (FC) of (n-3)FAD rats (P < 0.05). Dopa decarboxylase was downregulated in the hippocampus of ID and ID+(n-3)FAD rats (fold-change = -1.33; P < 0.05). ID and (n-3)FAD significantly impaired working memory performance and the impairment positively correlated with DA concentrations in FC (r = 0.39; P = 0.026). Reference memory was impaired in the ID+(n-3)FAD rats (P < 0.05) and was negatively associated with 5-HT in FC (r = -0.42; P = 0.018). These results suggest that the combined deficiencies of Fe and (n-3) FA disrupt brain monoamine metabolism and produce greater deficits in reference memory than ID or (n-3)FAD alone.
Effects of dietary saturated and n-6 polyunsaturated fatty acids on the incorporation of long-chain n-3 polyunsaturated fatty acids into blood lipids.

PubMed

Dias, C B; Wood, L G; Garg, M L

2016-07-01

Omega-3 polyunsaturated fatty acids (n-3PUFA) are better absorbed when they are combined with high-fat meals. However, the role of different dietary fats in modulating the incorporation of n-3PUFA in blood lipids in humans has not been previously explored. Omega-6 polyunsaturated fatty acids (n-6PUFA) are known to compete with n-3PUFA in the metabolic pathways and for the incorporation into phospholipids, whereas saturated fats (SFA) may enhance n-3PUFA incorporation into tissues. In a randomized parallel-design trial, we aimed to investigate the long-term effects of n-3PUFA supplementation in subjects consuming a diet enriched with either SFA or n-6PUFA on fatty acid incorporation into plasma and erythrocytes and on blood lipid profiles (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides). Dietary supplementation with n-3PUFA co-administered with SFA for 6 weeks resulted in a significant rise in total cholesterol (0.46±0.60 mmol/L; P=0.020) and LDL-C (0.48±0.48 mmol/L; P=0.011) in comparison with combination with n-6PUFA. The diet enriched with SFA also induced a greater increase in eicosapentaenoic acid (2.07±0.79 vs 1.15±0.53; P=0.004), a smaller decrease in docosapentaenoic acid (-0.12±0.23 vs -0.30±0.20; P=0.034) and a similar increase in docosahexaenoic acid (3.85±1.14 vs 3.10±1.07; P=0.128) percentage in plasma compared with the diet enriched with n-6PUFA. A similar effect was seen in erythrocytes. N-3PUFA supplementation resulted in similar changes in HDL-C and triglyceride levels. The results suggest that dietary substitution of SFA with n-6PUFA, despite maintaining low levels of circulating cholesterol, hinders n-3PUFA incorporation into plasma and tissue lipids.
Precision Nutrition and Omega-3 Polyunsaturated Fatty Acids: A Case for Personalized Supplementation Approaches for the Prevention and Management of Human Diseases

PubMed Central

Chilton, Floyd H.; Dutta, Rahul; Reynolds, Lindsay M.; Sergeant, Susan; Mathias, Rasika A.; Seeds, Michael C.

2017-01-01

Background: Dietary essential omega-6 (n-6) and omega-3 (n-3) 18 carbon (18C-) polyunsaturated fatty acids (PUFA), linoleic acid (LA) and α-linolenic acid (ALA), can be converted (utilizing desaturase and elongase enzymes encoded by FADS and ELOVL genes) to biologically-active long chain (LC; >20)-PUFAs by numerous cells and tissues. These n-6 and n-3 LC-PUFAs and their metabolites (ex, eicosanoids and endocannabinoids) play critical signaling and structural roles in almost all physiologic and pathophysiologic processes. Methods: This review summarizes: (1) the biosynthesis, metabolism and roles of LC-PUFAs; (2) the potential impact of rapidly altering the intake of dietary LA and ALA; (3) the genetics and evolution of LC-PUFA biosynthesis; (4) Gene–diet interactions that may lead to excess levels of n-6 LC-PUFAs and deficiencies of n-3 LC-PUFAs; and (5) opportunities for precision nutrition approaches to personalize n-3 LC-PUFA supplementation for individuals and populations. Conclusions: The rapid nature of transitions in 18C-PUFA exposure together with the genetic variation in the LC-PUFA biosynthetic pathway found in different populations make mal-adaptations a likely outcome of our current nutritional environment. Understanding this genetic variation in the context of 18C-PUFA dietary exposure should enable the development of individualized n-3 LC-PUFA supplementation regimens to prevent and manage human disease. PMID:29068398
The dietary n6:n3 fatty acid ratio during pregnancy is inversely associated with child neurodevelopment in the EDEN mother-child cohort.

PubMed

Bernard, Jonathan Y; De Agostini, Maria; Forhan, Anne; de Lauzon-Guillain, Blandine; Charles, Marie-Aline; Heude, Barbara

2013-09-01

Long-chain polyunsaturated fatty acids (LC-PUFAs) of the n6 (ω6) and n3 series are essential for the development of a child's brain. Fetal LC-PUFA exposure as well as infant exposure via breast milk depend on the maternal intake of these LC-PUFAs and of their respective dietary precursors (PUFAs). We aimed to investigate the associations between maternal LC-PUFA and PUFA [(LC)PUFA] dietary intake during pregnancy and child neurodevelopment at ages 2 and 3 y. In 1335 mother-child pairs from the EDEN cohort, we evaluated associations between daily maternal (LC)PUFA intake during the last 3 months of pregnancy with the child's language at age 2 y and with different assessments of development at age 3 y. Associations were investigated separately in breastfed and never-breastfed children. We examined interactions between the ratios of n6 and n3 (LC)PUFA intakes (n6:n3 fatty acid ratio) and duration of breastfeeding. Breastfeeding mothers had a lower n6:n3 fatty acid ratio (8.4 vs. 8.8; P = 0.02). Among never-breastfed children (n = 338), we found negative associations between maternal dietary n6:n3 fatty acid ratios and neurodevelopment, as reflected by the child's language at age 2 y (β ± SE = -2.1 ± 0.7; P = 0.001) and development assessed with the Ages and Stages Questionnaire at age 3 y (-1.5 ± 0.8; P = 0.05). Among mothers with a high n6:n3 fatty acid ratio only, breastfeeding duration was positively associated with language at age 2 y (P-interaction < 0.05). This suggests that the ratio between maternal dietary n6 and n3 (LC)PUFA intake possibly influences the child's brain development during fetal life but not during or by breastfeeding. However, breastfeeding might compensate for prenatal imbalance in maternal dietary n6:n3 fatty acid ratio.
Therapeutic potential of n-3 polyunsaturated fatty acids in disease.

PubMed

Fetterman, James W; Zdanowicz, Martin M

2009-07-01

The potential therapeutic benefits of supplementation with n-3 polyunsaturated fatty acids (PUFAs) in various diseases are reviewed, and the antiinflammatory actions, activity, and potential drug interactions and adverse effects of n-3 PUFAs are discussed. Fish oils are an excellent source of long-chain n-3 PUFAs, such as eicosapentaenoic acid and docosahexaenoic acid. After consumption, n-3 PUFAs can be incorporated into cell membranes and reduce the amount of arachidonic acid available for the synthesis of proinflammatory eicosanoids (e.g., prostaglandins, leukotrienes). Likewise, n-3 PUFAs can also reduce the production of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1, and interleukin-6. Considerable research has been conducted to evaluate the potential therapeutic effects of fish oils in numerous conditions, including arthritis, coronary artery disease, inflammatory bowel disease, asthma, and sepsis, all of which have inflammation as a key component of their pathology. Additional investigations into the use of supplementation with fish oils in patients with neural injury, cancer, ocular diseases, and critical illness have recently been conducted. The most commonly reported adverse effects of fish oil supplements are a fishy aftertaste and gastrointestinal upset. When recommending an n-3 PUFA, clinicians should be aware of any possible adverse effect or drug interaction that, although not necessarily clinically significant, may occur, especially for patients who may be susceptible to increased bleeding (e.g., patients taking warfarin). The n-3 PUFAs have been shown to be efficacious in treating and preventing various diseases. The wide variation in dosages and formulations used in studies makes it difficult to recommend dosages for specific treatment goals.
Olfactory discrimination ability and brain expression of c-fos, Gir and Glut1 mRNA are altered in n-3 fatty acid-depleted rats.

PubMed

Hichami, Aziz; Datiche, Frédérique; Ullah, Sana; Liénard, Fabienne; Chardigny, Jean-Michel; Cattarelli, Martine; Khan, Naim Akhtar

2007-11-22

The long-chain polyunsaturated n-3 fatty acids (n-3 PUFA), particularly docosahexaenoic acid (DHA), are abundantly present in the central nervous system and play an important role in cognitive functions such as learning and memory. We, therefore, investigated the effects of n-3 PUFA-depletion in rats (F2 generation) on the learning of an olfactory discrimination task, progressively acquired within a four-arm maze, and on the mRNA expression of some candidate genes, i.e., c-fos, Gir and glucose transporter (Glut1), which could reflect the level of cerebral activity. We observed that DHA contents were dramatically decreased in the olfactory bulb, the piriform cortex and the neocortex of n-3-depleted rats. Furthermore, the n-3 deficiency resulted in a mild olfactory learning impairment as these rats required more days to master the olfactory task compared to control rats. Real-time RT-PCR experiments revealed that the training induced the expression of c-fos mRNA in all the three regions of the brain whereas Gir and Glut1 mRNA were induced only in olfactory bulb and neocortex. However, such an increase was less marked in the n-3-deficient rats. Taken together, these results allow us to assume that the behavioural impairment in n-3-deficient rats is linked to the depletion of n-3 fatty acids in brain regions processing olfactory cues. Data are discussed in view of the possible role of some of these genes in learning-induced neuronal olfactory plasticity.
Enriched endogenous n-3 polyunsaturated fatty acids alleviate cognitive and behavioral deficits in a mice model of Alzheimer's disease.

PubMed

Wu, Kefeng; Gao, Xiang; Shi, Baoyan; Chen, Shiyu; Zhou, Xin; Li, Zhidong; Gan, Yuhong; Cui, Liao; Kang, Jing Xuan; Li, Wende; Huang, Ren

2016-10-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accompanied by memory deficits and neuropsychiatric dysfunction. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have seemly therapeutic potential in AD, but the benefit of n-3 PUFAs is still in debates. Here, we employed a transgenic mice carry fat-1 gene to encode n-3 desaturase from Caenorhabditis elegans, which increase endogenous n-3 PUFAs by converting n-6 PUFAs to n-3 PUFAs crossed with amyloid precursor protein (APP) Tg mice to evaluate the protective effects of endogenous n-3 PUFAs on cognitive and behavioral deficits of APP Tg mice. We fed APP, APP/fat-1 and fat-1 mice with n-6 PUFAs rich diet. Brain tissues were collected at 3, 9 and 12 months for fatty acid and gene expression analysis, histology and protein assays. Morris Water Maze Test, open field test and elevated plus maze test were performed to measure the behavior capability. From the results, the expression of fat-1 transgene increased cortical n-3: n-6 PUFAs ratio and n-3 PUFAs concentrations, and sensorimotor dysfunction and cognitive deficits in AD were significantly less severe in APP/fat-1 mice with endogenous n-3 PUFAs than in APP mice controls. The protection against disturbance of spontaneous motor activity and cognitive deficits in AD was strongly correlated with increased n-3: n-6 PUFAs ratio and endogenous n-3 PUFAs, reduced APP generation, inhibited amyloid β peptide aggregation, suppressed nuclear factor-kappa B and astroglia activation, and reduced death of neurons in the cortex of APP/fat-1 mice compared with APP mice controls. In conclusion, our study demonstrates that an available medication with the maintenance of enriched n-3 PUFAs in the brain could slow down cognitive decline and prevent neuropsychological disorder in AD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
Dietary n-6:n-3 Fatty Acid Ratios Alter Rumen Fermentation Parameters and Microbial Populations in Goats.

PubMed

Ebrahimi, Mahdi; Rajion, Mohamed Ali; Adeyemi, Kazeem Dauda; Jafari, Saeid; Jahromi, Mohammad Faseleh; Oskoueian, Ehsan; Meng, Goh Yong; Ghaffari, Morteza Hosseini

2017-02-01

Revealing the ruminal fermentation patterns and microbial populations as affected by dietary n-6:n-3 PUFA ratio would be useful for further clarifying the role of the rumen in the lipid metabolism of ruminants. The objective of the present study was to investigate the effects of dietary n-6:n-3 PUFA ratios on fermentation characteristics, fatty acid (FA) profiles, and microbial populations in the rumen of goats. A total of twenty-one goats were randomly assigned to three dietary treatments with different n-6:n-3 PUFA ratios of 2.27:1 (low ratio, LR), 5.01:1 (medium ratio, MR), and 10.38:1 (high ratio, HR). After 100 days of feeding, all goats were slaughtered. Dietary n-6:n-3 PUFA ratios had no effect (P > 0.05) on rumen pH and NH 3 N concentration. Goats fed HR diet had lower (P < 0.05) propionate and total volatile fatty acids and higher (P < 0.05) butyrate compared with those fed the MR and LR diets. The proportion of C18:0 decreased (P < 0.05) as dietary n-6:n-3 PUFA ratios increased. The proportions of C18:1 trans-11, C18:2n-6, cis-9 trans-11 CLA, and C20:4n-6 were greater in the HR goats compared with the MR and LR goats. Lowering dietary n-6:n-3 PUFA ratios enhanced (P < 0.05) the proportion of C18:3n-3 and total n-3 PUFA in the rumen fluid of goats. The populations of R. albus and R. flavefaciens decreased (P < 0.05) as the n-6:n-3 PUFA ratios increased in diet. Diet had no effect (P > 0.05) on the ruminal populations of F. succinogenes, total bacteria, methanogens, total protozoa, Entiodinium, and Holotrich. The population of B. fibrisolvens was lower (P < 0.05) in the LR goats compared with the MR and HR goats. It was concluded that HR would increase the concentration of cis-9 trans-11 CLA and C18:1 trans-11 in the rumen. However, LR whould decrease the B. fibrisolvens population, which is involved in the BH process in the rumen. Further research is needed to evaluate the potential role and contribution of rumen microbiome in the metabolism of FA in the
Dietary Supplementation with n-3 Polyunsaturated Fatty Acids Reduces Torpor Use in a Tropical Daily Heterotherm.

PubMed

Vuarin, Pauline; Henry, Pierre-Yves; Perret, Martine; Pifferi, Fabien

Polyunsaturated fatty acids (PUFAs) are involved in a variety of physiological mechanisms, including heterothermy preparation and expression. However, the effects of the two major classes of PUFAs, n-6 and n-3, can differ substantially. While n-6 PUFAs enhance torpor expression, n-3 PUFAs reduce the ability to decrease body temperature. This negative impact of n-3 PUFAs has been revealed in temperate hibernators only. Yet because tropical heterotherms generally experience higher ambient temperature and exhibit higher minimum body temperature during heterothermy, they may not be affected as much by PUFAs as their temperate counterparts. We tested whether n-3 PUFAs constrain torpor use in a tropical daily heterotherm (Microcebus murinus). We expected dietary n-3 PUFA supplementation to induce a reduction in torpor use and for this effect to appear rapidly given the time required for dietary fatty acids to be assimilated into phospholipids. n-3 PUFA supplementation reduced torpor use, and its effect appeared in the first days of the experiment. Within 2 wk, control animals progressively deepened their torpor bouts, whereas supplemented ones never entered torpor but rather expressed only constant, shallow reductions in body temperature. For the rest of the experiment, the effect of n-3 PUFA supplementation on torpor use remained constant through time. Even though supplemented animals also started to express torpor, they exhibited higher minimum body temperature by 2°-3°C and spent two fewer hours in a torpid state per day than control individuals, on average. Our study supports the view that a higher dietary content in n-3 PUFAs negatively affects torpor use in general, not only in cold-acclimated hibernators.
Hepatic fat accumulation is modulated by the interaction between the rs738409 variant in the PNPLA3 gene and the dietary omega6/omega3 PUFA intake.

PubMed

Santoro, Nicola; Savoye, Mary; Kim, Grace; Marotto, Katie; Shaw, Melissa M; Pierpont, Bridget; Caprio, Sonia

2012-01-01

A single nucleotide polymorphism (SNP), the rs738409, in the patatin like phospholipase 3 gene (PNPLA3) has been recently associated with increased hepatic steatosis and ALT levels in adults and children. Given the potential role of PNPLA3 in fatty liver development, we aimed to explore whether the influence of PNPLA3 genotype on hepatic fat in obese youth might be modulated by dietary factors such as essential omega polyunsaturated fatty acids (PUFA) intake. We studied 127 children and adolescents (56 boys, 71 girls; 58 Caucasians; 30 African Americans and 39 Hispanics; mean age 14.7±3.3; mean BMI 30.7±7.2). The dietary composition was assessed by the Nutrition Data System for Research (NDS-R version 2011). The patients underwent a MRI study to assess the liver fat content (HFF%), ALT measurement and the genotyping of the rs738409 SNP by automatic sequencing. As previously observed, HFF% and ALT levels varied according to the genotype in each ethnicity. ALT levels and HFF% were significantly influenced by the interaction between genotype and omega-6/omega-3 PUFA ratio (n-6/n-3), p = 0.003 and p = 0.002, respectively. HFF% and ALT levels were, in fact, related to the n-6/n-3 consumption only in subjects homozygote for the G allele of the rs738409 (r2 = 0.45, p = 0.001 and r2 = 0.40, p = 0.006, respectively). These findings suggest that the association of a high dietary n-6/n-3 PUFA with fatty liver and liver damage in obese youths may be driven by a predisposing genotype.
Dietary omega-3 PUFA and health: stearidonic acid-containing seed oils as effective and sustainable alternatives to traditional marine oils.

PubMed

Surette, Marc E

2013-05-01

The daily consumption of dietary omega-3 PUFA is recommended by governmental agencies in several countries and by a number of health organizations. The molecular mechanisms by which these dietary PUFA affect health involve the enrichment of cellular membranes with long-chain 20- and 22-carbon omega-3 PUFA that impacts tissues by altering membrane protein functions, cell signaling, and gene expression profiles. These changes are recognized to have health benefits in humans, especially relating to cardiovascular outcomes. Cellular membrane enrichment and health benefits are associated with the consumption of long-chain omega-3 PUFA found in marine oils, but are not generally linked with the consumption of alpha-linolenic acid, the 18-carbon omega-3 PUFA found in plant seed oils. However, the supply of omega-3 PUFA from marine sources is limited and may not be sustainable. New plant-derived sources of omega-3 PUFA like stearidonic acid-soy oil from genetically modified soybeans and Ahiflower oil from Buglossoides arvensis seeds that are enriched in the 18-carbon omega-3 PUFA stearidonic acid are being developed and show promise to become effective as well as sustainable sources of omega-3 PUFA. An example of changes in tissue lipid profiles associated with the consumption of Ahiflower oil is presented in a mouse feeding study. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Polyunsaturated Fatty Acids and Recurrent Mood Disorders: Phenomenology, Mechanisms, and Clinical Application

PubMed Central

Messamore, Erik; Almeida, Daniel M.; Jandacek, Ronald J.; McNamara, Robert K.

2017-01-01

A body of evidence has implicated dietary deficiency in omega-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and etiology of recurrent mood disorders including major depressive disorder (MDD) and bipolar disorder. Cross-national and cross-sectional evidence suggests that greater habitual intake of n-3 PUFA is associated with reduced risk for developing mood symptoms. Meta-analyses provide strong evidence that patients with mood disorders exhibit low blood n-3 PUFA levels which are associated with increased risk for the initial development of mood symptoms in response to inflammation. While the etiology of this n-3 PUFA deficit may be multifactorial, n-3 PUFA supplementation is sufficient to correct this deficit and may also have antidepressant effects. Rodent studies suggest that n-3 PUFA deficiency during perinatal development can recapitulate key neuropathological, neurochemical, and behavioral features associated with mood disorders. Clinical neuroimaging studies suggest that low n-3 PUFA biostatus is associated with abnormalities in cortical structure and function also observed in mood disorders. Collectively, these findings implicate dietary n-3 PUFA insufficiency, particularly during development, in the pathophysiology of mood dysregulation, and support implementation of routine screening for and treatment of n-3 PUFA deficiency in patients with mood disorders. PMID:28069365
Bioavailability of long-chain n-3 fatty acids from enriched meals and from microencapsulated powder.

PubMed

Hinriksdottir, H H; Jonsdottir, V L; Sveinsdottir, K; Martinsdottir, E; Ramel, A

2015-03-01

Despite the potential benefits of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), intake is often low because of low consumption of oily seafood. Microencapsulated fish oil powder can improve tolerance and acceptance of LC n-3 PUFAs. Bioavailability is important to achieve efficacy. We investigated the bioavailability of LC n-3 PUFAs from microencapsulated powder in comparison with meals enriched with liquid fish oil. Participants (N=99, age⩾50 years) of this 4-week double-blinded dietary intervention were randomized into three groups. Group 1 (n=38) received 1.5 g/d eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as ready-to-eat meals enriched with liquid fish oil; group 2 (n=30) received the same amount of these LC n-3 PUFAs as microencapsulated fish oil powder and regular meals; and group 3 (n=31) was the control group, which received placebo powder and regular meals. Blood samples were taken from fingertips at baseline and at the end point. Seventy-seven subjects (77.8%) completed the study. The amount of EPA in blood doubled in both groups that received LC n-3 PUFAs (P<0.05), but it did not change in the control group. The changes in DHA were less but still significant in both intervention groups. According to multivariate analysis, both intervention groups had higher end-point LC n-3 PUFA concentrations compared with placebo, but differences between intervention groups were not significant. Bioavailability of LC n-3 PUFAs in encapsulated powder is very similar to the bioavailability of LC n-3 PUFAs in ready-to-eat meals enriched with liquid fish oil. Thus, encapsulated powder can be considered useful to increase LC n-3 PUFA concentrations in blood.
The marine n-3 PUFA DHA evokes cytoprotection against oxidative stress and protein misfolding by inducing autophagy and NFE2L2 in human retinal pigment epithelial cells

PubMed Central

Johansson, Ida; Monsen, Vivi Talstad; Pettersen, Kristine; Mildenberger, Jennifer; Misund, Kristine; Kaarniranta, Kai; Schønberg, Svanhild; Bjørkøy, Geir

2015-01-01

Accumulation and aggregation of misfolded proteins is a hallmark of several diseases collectively known as proteinopathies. Autophagy has a cytoprotective role in diseases associated with protein aggregates. Age-related macular degeneration (AMD) is the most common neurodegenerative eye disease that evokes blindness in elderly. AMD is characterized by degeneration of retinal pigment epithelial (RPE) cells and leads to loss of photoreceptor cells and central vision. The initial phase associates with accumulation of intracellular lipofuscin and extracellular deposits called drusen. Epidemiological studies have suggested an inverse correlation between dietary intake of marine n-3 polyunsaturated fatty acids (PUFAs) and the risk of developing neurodegenerative diseases, including AMD. However, the disease-preventive mechanism(s) mobilized by n-3 PUFAs is not completely understood. In human retinal pigment epithelial cells we find that physiologically relevant doses of the n-3 PUFA docosahexaenoic acid (DHA) induce a transient increase in cellular reactive oxygen species (ROS) levels that activates the oxidative stress response regulator NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2). Simultaneously, there is a transient increase in intracellular protein aggregates containing SQSTM1/p62 (sequestosome 1) and an increase in autophagy. Pretreatment with DHA rescues the cells from cell cycle arrest induced by misfolded proteins or oxidative stress. Cells with a downregulated oxidative stress response, or autophagy, respond with reduced cell growth and survival after DHA supplementation. These results suggest that DHA both induces endogenous antioxidants and mobilizes selective autophagy of misfolded proteins. Both mechanisms could be relevant to reduce the risk of developing aggregate-associate diseases such as AMD. PMID:26237736
Red blood cell n-3 polyunsaturated fatty acids in first trimester of pregnancy are inversely associated with placental weight.

PubMed

Magnusardottir, Anna R; Steingrimsdottir, Laufey; Thorgeirsdottir, Holmfridur; Hauksson, Arnar; Skuladottir, Gudrun V

2009-01-01

To investigate pregnancy outcome in relation to red blood cell (RBC) level of long-chain n-3 polyunsaturated fatty acids (PUFA) in the first trimester of pregnancy and the influence of lifestyle factors on the RBC level of long-chain n-3 PUFA. Observational study in a community with traditional fish and cod liver oil consumption. Seventy-seven healthy pregnant women. The PUFA composition of RBC was measured in the 11th to 15th week of pregnancy. The women answered food frequency and lifestyle questionnaires. Information on pregnancy outcome was collected from birth records. Placental weight, long-chain n-3 PUFA in diet and RBC, smoking. Of all the pregnancy outcome variables tested, placental weight was the only one associated with long-chain n-3 PUFA in RBC. Inverse association was found between the proportion of long-chain n-3 PUFA in RBC and placental weight, adjusted for birthweight (p=0.035). The proportion of long-chain n-3 PUFA in RBC was positively related to long-chain n-3 PUFA intake (p<0.001) and negatively related to smoking (p=0.011). The human fetus relies on maternal supply and placental delivery of long-chain n-3 PUFA for optimal development and function, particularly of the central nervous system. Given the importance of dietary n-3 PUFA during pregnancy, further studies are warranted to investigate the relationship between placental weight, maternal long-chain n-3 PUFA status and smoking.
Hepatic Fat Accumulation Is Modulated by the Interaction between the rs738409 Variant in the PNPLA3 Gene and the Dietary Omega6/Omega3 PUFA Intake

PubMed Central

Santoro, Nicola; Savoye, Mary; Kim, Grace; Marotto, Katie; Shaw, Melissa M.; Pierpont, Bridget; Caprio, Sonia

2012-01-01

Background A single nucleotide polymorphism (SNP), the rs738409, in the patatin like phospholipase 3 gene (PNPLA3) has been recently associated with increased hepatic steatosis and ALT levels in adults and children. Given the potential role of PNPLA3 in fatty liver development, we aimed to explore whether the influence of PNPLA3 genotype on hepatic fat in obese youth might be modulated by dietary factors such as essential omega polyunsaturated fatty acids (PUFA) intake. Materials and Methods We studied 127 children and adolescents (56 boys, 71 girls; 58 Caucasians; 30 African Americans and 39 Hispanics; mean age 14.7±3.3; mean BMI 30.7±7.2). The dietary composition was assessed by the Nutrition Data System for Research (NDS-R version 2011). The patients underwent a MRI study to assess the liver fat content (HFF%), ALT measurement and the genotyping of the rs738409 SNP by automatic sequencing. Results As previously observed, HFF% and ALT levels varied according to the genotype in each ethnicity. ALT levels and HFF% were significantly influenced by the interaction between genotype and omega-6/omega-3 PUFA ratio (n-6/n-3), p = 0.003 and p = 0.002, respectively. HFF% and ALT levels were, in fact, related to the n-6/n-3 consumption only in subjects homozygote for the G allele of the rs738409 (r2 = 0.45, p = 0.001 and r2 = 0.40, p = 0.006, respectively). Conclusions These findings suggest that the association of a high dietary n-6/n-3 PUFA with fatty liver and liver damage in obese youths may be driven by a predisposing genotype. PMID:22629460

Cognitive antecedents of consumers' willingness to purchase fish rich in polyunsaturated fatty acids (PUFA).

PubMed

Foxall, G; Leek, S; Maddock, S

1998-12-01

A sample of UK consumers (N = 311) was interviewed in order to identify the attitudinal, cognitive and involvement characteristics of probable early adopters of polyunsaturated fatty acid (PUFA) fed fish. Attitude to fish significantly influenced PUFA fish, premium price PUFA fish, PUFA salmon, PUFA eel and PUFA sturgeon purchase. Involvement in healthy eating influenced PUFA fish, premium price PUFA fish and PUFA salmon purchase. Cognitive style did not influence PUFA fish and premium price PUFA fish purchase; nor, contrary to earlier research, did cognitive style and involvement interact to influence intended PUFA fish purchases.
ω-3 PUFAs ameliorate liver fibrosis and inhibit hepatic stellate cells proliferation and activation by promoting YAP/TAZ degradation.

PubMed

Zhang, Kun; Chang, Yanan; Shi, Zhemin; Han, Xiaohui; Han, Yawei; Yao, Qingbin; Hu, Zhimei; Cui, Hongmei; Zheng, Lina; Han, Tao; Hong, Wei

2016-07-20

Elevated levels of the transcriptional regulators Yes-associated protein (YAP) and transcriptional coactivators with PDZ-binding motif (TAZ), key effectors of the Hippo pathway, have been shown to play essential roles in controlling liver cell fate and the activation of hepatic stellate cells (HSCs). The dietary intake of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) has been positively associated with a number of health benefits including prevention and reduction of cardiovascular diseases, inflammation and cancers. However, little is known about the impact of ω-3 PUFAs on liver fibrosis. In this study, we used CCl4-induced liver fibrosis mouse model and found that YAP/TAZ is over-expressed in the fibrotic liver and activated HSCs. Fish oil administration to the model mouse attenuates CCl4-induced liver fibrosis. Further study revealed that ω-3 PUFAs down-regulate the expression of pro-fibrogenic genes in activated HSCs and fibrotic liver, and the down-regulation is mediated via YAP, thus identifying YAP as a target of ω-3 PUFAs. Moreover, ω-3 PUFAs promote YAP/TAZ degradation in a proteasome-dependent manner. Our data have identified a mechanism of ω-3 PUFAs in ameliorating liver fibrosis.
Health benefits of n-3 polyunsaturated fatty acids: eicosapentaenoic acid and docosahexaenoic acid.

PubMed

Siriwardhana, Nalin; Kalupahana, Nishan S; Moustaid-Moussa, Naima

2012-01-01

Marine-based fish and fish oil are the most popular and well-known sources of n-3 polyunsaturated fatty acids (PUFAs), namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These n-3 PUFAs are known to have variety of health benefits against cardiovascular diseases (CVDs) including well-established hypotriglyceridemic and anti-inflammatory effects. Also, various studies indicate promising antihypertensive, anticancer, antioxidant, antidepression, antiaging, and antiarthritis effects. Moreover, recent studies also indicate anti-inflammatory and insulin-sensitizing effects of these fatty acids in metabolic disorders. Classically, n-3 PUFAs mediate some of these effects by antagonizing n-6 PUFA (arachidonic acid)-induced proinflammatory prostaglandin E₂ (PGE₂) formation. Another well-known mechanism by which n-3 PUFAs impart their anti-inflammatory effects is via reduction of nuclear factor-κB activation. This transcription factor is a potent inducer of proinflammatory cytokine production, including interleukin 6 and tumor necrosis factor-α, both of which are decreased by EPA and DHA. Other evidence also demonstrates that n-3 PUFAs repress lipogenesis and increase resolvins and protectin generation, ultimately leading to reduced inflammation. Finally, beneficial effects of EPA and DHA in insulin resistance include their ability to increase secretion of adiponectin, an anti-inflammatory adipokine. In summary, n-3 PUFAs have multiple health benefits mediated at least in part by their anti-inflammatory actions; thus their consumption, especially from dietary sources, should be encouraged. Copyright Â© 2012 Elsevier Inc. All rights reserved.
Alternative Sources of n-3 Long-Chain Polyunsaturated Fatty Acids in Marine Microalgae

PubMed Central

Martins, Dulce Alves; Custódio, Luísa; Barreira, Luísa; Pereira, Hugo; Ben-Hamadou, Radhouan; Varela, João; Abu-Salah, Khalid M.

2013-01-01

The main source of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in human nutrition is currently seafood, especially oily fish. Nonetheless, due to cultural or individual preferences, convenience, geographic location, or awareness of risks associated to fatty fish consumption, the intake of fatty fish is far from supplying the recommended dietary levels. The end result observed in most western countries is not only a low supply of n-3 LC-PUFA, but also an unbalance towards the intake of n-6 fatty acids, resulting mostly from the consumption of vegetable oils. Awareness of the benefits of LC-PUFA in human health has led to the use of fish oils as food supplements. However, there is a need to explore alternatives sources of LC-PUFA, especially those of microbial origin. Microalgae species with potential to accumulate lipids in high amounts and to present elevated levels of n-3 LC-PUFA are known in marine phytoplankton. This review focuses on sources of n-3 LC-PUFA, namely eicosapentaenoic and docosahexaenoic acids, in marine microalgae, as alternatives to fish oils. Based on current literature, examples of marketed products and potentially new species for commercial exploitation are presented. PMID:23807546
Light Intensity Regulates LC-PUFA Incorporation into Lipids of Pavlova lutheri and the Final Desaturase and Elongase Activities Involved in Their Biosynthesis.

PubMed

Guihéneuf, Freddy; Mimouni, Virginie; Tremblin, Gérard; Ulmann, Lionel

2015-02-04

The microalga Pavlova lutheri is a candidate for the production of omega-3 long-chain polyunsaturated fatty acid (LC-PUFA), due to its ability to accumulate both eicosapentaenoic (EPA) and docosahexaenoic acids. Outstanding questions need to be solved to understand the complexity of n-3 LC-PUFA synthesis and partitioning into lipids, especially its metabolic regulation, and which enzymes and/or abiotic factors control their biosynthesis. In this study, the radioactivity of 14 C-labeled arachidonic acid incorporated into the total lipids of P. lutheri grown under different light intensities and its conversion into labeled LC-PUFA were monitored. The results highlighted for the first time the light-dependent incorporation of LC-PUFA into lipids and the light-dependent activity of the final desaturation and elongation steps required to synthesize and accumulate n-3 C20/C22 LC-PUFA. The incorporation of arachidonic acid into lipids under low light and the related Δ17-desaturation activity measured explain the variations in fatty acid profile of P. lutheri, especially the accumulation of n-3 LC-PUFA such as EPA under low light conditions.
The Role of n-3 Polyunsaturated Fatty Acids in the Prevention and Treatment of Breast Cancer

PubMed Central

Liu, Jiajie; Ma, David W. L.

2014-01-01

Breast cancer (BC) is the most common cancer among women worldwide. Dietary fatty acids, especially n-3 polyunsaturated fatty acids (PUFA), are believed to play a role in reducing BC risk. Evidence has shown that fish consumption or intake of long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for inhibiting mammary carcinogenesis. The evidence regarding α-linolenic acid (ALA), however, remains equivocal. It is essential to clarify the relation between ALA and cancer since ALA is the principal source of n-3 PUFA in the Western diet and the conversion of ALA to EPA and DHA is not efficient in humans. In addition, the specific anticancer roles of individual n-3 PUFA, alone, have not yet been identified. Therefore, the present review evaluates ALA, EPA and DHA consumed individually as well as in n-3 PUFA mixtures. Also, their role in the prevention of BC and potential anticancer mechanisms of action are examined. Overall, this review suggests that each n-3 PUFA has promising anticancer effects and warrants further research. PMID:25412153
Effect of n-3 PUFA supplementation at different EPA:DHA ratios on the spontaneously hypertensive obese rat model of the metabolic syndrome.

PubMed

Molinar-Toribio, Eunice; Pérez-Jiménez, Jara; Ramos-Romero, Sara; Romeu, Marta; Giralt, Montserrat; Taltavull, Núria; Muñoz-Cortes, Mònica; Jáuregui, Olga; Méndez, Lucía; Medina, Isabel; Torres, Josep Lluís

2015-03-28

The increasing incidence of the metabolic syndrome (MetS), a combination of risk factors before the onset of CVD and type 2 diabetes, encourages studies on the role of functional food components such as long-chain n-3 PUFA as preventive agents. In the present study, we explore the effect of EPA and DHA supplementation in different proportions on spontaneously hypertensive obese (SHROB) rats, a model for the MetS in a prediabetic state with mild oxidative stress. SHROB rats were randomised into four groups (n 7), each supplemented with EPA/DHA at ratios of 1:1, 2:1 and 1:2, or soyabean oil as the control for 13 weeks. The results showed that in all the proportions tested, EPA/DHA supplementation significantly lowered total and LDL-cholesterol concentrations, compared with those of the control group. EPA/DHA supplementation at the ratios of 1:1 and 2:1 significantly decreased inflammation (C-reactive protein levels) and lowered oxidative stress (decreased excretion of urinary isoprostanes), mainly at the ratio of 1:2. The activity of antioxidant enzymes increased in erythrocytes, abdominal fat and kidneys, with magnitudes depending on the EPA:DHA ratio. PUFA mixtures from fish affected different MetS markers of CVD risk factors in SHROB rats, depending on the ratios of EPA/DHA supplementation. The activation of endogenous defence systems may be related to the reduction of inflammation and oxidative stress.
Production and Dietary Uptake of PUFA by Piezophilic Bacteria, Implications for Marine Biogeochemistry

NASA Astrophysics Data System (ADS)

Fang, J.; Chan, O.; Agarkar, N.; Kato, C.; Sato, T.

2003-12-01

Polyunsaturated fatty acids (PUFAs) have been used extensively as proxies for determining the source and preservation of organic matter in marine sediments. However, the origin of polyunsaturated fatty acids in deep-sea sediments is not well understood; the ultimate source of PUFAs is only partially constrained. At issue is whether PUFAs in deep-sea sediments are derived from the primary production of the photic zone or from the in situ piezophilic bacterial production in the deep-sea, or both. In this study, we tested three deep-sea piezophilic strains, Shewanella violacea DSS12, Shewanella benthica DB21MT-2, Moritella yayanosii DB21MT-5, in biosynthesis and dietary uptake of PUFAs. These piezophilic bacteria were characterized by high abundance of unsaturated fatty acids (62-73% of total fatty acids). In particularly, polyunsaturated fatty acids (PUFA) were detected in all piezophiles examined, ranging from 8 to 27% of total fatty acids. M. japonica DSK1 produced 22:6n-3 (cis-4,7,10,13,16,19-docosahexaenoic acid, DHA), whereas the three Shewanella strains produced 20:5n-3 (cis-5,8,11,14,17-eicosapentaenoic acid, EPA) with trace amounts of DHA. The total concentrations of PLFA were higher in strains grown at low pressure (DSK1, 10 Megapascal or MPa, 26,983μ g/g dry wt cells; DSS12, 50 MPa, 23,986 μ g/g), and lower in strains grown at high pressure (DB6705, 85 MPa, 1,901μ g/g; DB21MT-2, 100 MPa, 3,014 μ g/g). When growth media were supplemented with arachidonic acid (AA; C20:4n-6), there was active uptake and cellular incorporation of AA in the hyperpiezophilic bacteria DB21MT-2 (14.7%) and DB21MT-5 (1.4%). No uptake was observed in DSS12. When cells were treated with antibiotic cerulenin, all three strains incorporated AA into cell membranes (13 to 19%). These results suggest that piezophilic bacteria can be an important contributor in producing and reworking of PUFAs in the deep sea, and that that caution must be exercised in using PUFAs in deducing sources
Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study

USDA-ARS?s Scientific Manuscript database

In osteoarthritis (OA) the synovium is often inflamed and inflammatory cytokines contribute to cartilage damage. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory effects whereas omega-6 polyunsaturated fatty acids (n-6 PUFAs) have, on balance, proinflammatory effects. The goal ...
Obesity development in neuron-specific lipoprotein lipase deficient mice is not responsive to increased dietary fat content or change in fat composition.

PubMed

Wang, Hong; Taussig, Matthew D; DiPatrizio, Nicholas V; Bruce, Kimberley; Piomelli, Daniele; Eckel, Robert H

2016-07-01

We have previously reported that mice with neuron-specific LPL deficiency (NEXLPL-/-) become obese by 16weeks of age on chow. Moreover, these mice had reduced uptake of triglyceride (TG)-rich lipoprotein-derived fatty acids and lower levels of n-3 long chain polyunsaturated fatty acids (n-3 PUFAs) in the hypothalamus. Here, we asked whether increased dietary fat content or altered dietary composition could modulate obesity development in NEXLPL-/- mice. Male NEXLPL-/- mice and littermate controls (WT) were randomly assigned one of three synthetic diets; a high carbohydrate diet (HC, 10% fat), a high-fat diet (HF, 45% fat), or a HC diet supplemented with n-3 PUFAs (HCn-3, 10% fat, Lovaza, GSK®). After 42weeks of HC feeding, body weight and fat mass were increased in the NEXLPL-/- mice compared to WT. WT mice fed a HF diet displayed typical diet-induced obesity, but weight gain was only marginal in HF-fed NEXLPL-/- mice, with no significant difference in body composition. Dietary n-3 PUFA supplementation did not prevent obesity in NEXLPL-/- mice, but was associated with differential modifications in hypothalamic gene expression and PUFA concentration compared to WT mice. Our findings suggest that neuronal LPL is involved in the regulation of body weight and composition in response to either the change in quantity (HF feeding) or quality (n-3 PUFA-enriched) of dietary fat. The precise role of LPL in lipid sensing in the brain requires further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.
Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.

PubMed

Tan, May Loong; Ho, Jacqueline J; Teh, Keng Hwang

2012-12-12

About 5% of schoolchildren have a specific learning disorder, defined as an unexpected failure to acquire adequate abilities in reading, writing or mathematic skills not as a result of reduced intellectual ability, inadequate teaching or social deprivation. Of these, 80% are reading disorders. Polyunsaturated fatty acids (PUFAs), in particular omega-3 and omega-6 fatty acids, which are found abundantly in the brain and retina are important for learning. Some children with specific learning disorders have been found to be deficient in these PUFAs, and it is argued that supplementation of PUFAs may help these children improve their learning abilities. To assess the effects of polyunsaturated fatty acids (PUFAs) supplementation for children with specific learning disorders, on learning outcomes. We searched the following databases in April 2012: CENTRAL (2012, Issue 4), MEDLINE (1948 to April Week 2 2012), EMBASE (1980 to 2012 Week 16), PsycINFO (1806 to April 2012), ERIC (1966 to April 2012), Science Citation Index (1970 to 20 April 2012), Social Science Citation Index (1970 to 20 April 2012), Conference Proceedings Citation Index-Science (1970 to 20 April 2012), Conference Proceedings Citation Index-Social Sciences and Humanites (1970 to 20 April 2012), Cochrane Database of Systematic Reviews (2012, Issue 4), DARE (2012, Issue 2) , ZETOC (24 April 2012) and WorldCat (24 April 2012). We searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov on 24 April 2012. We also searched the reference lists of relevant articles identified by the searches. Randomised or quasi-randomised controlled trials comparing polyunsaturated fatty acids (PUFAs) with placebo or no treatment in children aged below 18 years with specific learning disabilities diagnosed using DSM-IV, ICD-10 or equivalent criteria. We intended to include participants with co-existing developmental disorders such as attention deficit hyperactivity disorder (ADHD) or autism. Two
Genetic Variants of the FADS Gene Cluster Are Associated with Erythrocyte Membrane LC PUFA Levels in Patients with Mild Cognitive Impairment.

PubMed

Schuchardt, J P; Köbe, T; Witte, V; Willers, J; Gingrich, A; Tesky, V; Pantel, J; Rujescu, D; Illig, T; Flöel, A; Hahn, A

2016-01-01

Long-chain (> 20 C-atoms) polyunsaturated fatty acids (LC PUFAs) of both the omega-6 (n-6) and omega-3 (n-3) series are important for the functional integrity of brain and thereby cognition, memory and mood. Clinical studies observed associations between altered LC PUFA levels and neurodegenerative diseases such as Alzheimer´s disease and its prodromal stage, mild cognitive impairment (MCI). The present study examined the LC PUFA status of MCI patients with specific view on the relative LC n-3 PUFA levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes (omega-3 index). 12 single nucleotide polymorphisms (SNPs) of the FADS1, FADS2, and FADS3 gene clusters were genotyped in 111 MCI patients and evaluated associations with PUFA levels in erythrocyte membranes (primary outcome). In addition, the associations between FADS SNPs and LC PUFA levels with serum lipid levels as well as depressive symptoms were examined (secondary outcomes). Minor allele carrier of rs174546, rs174548 (FADS1), rs3834458, rs1535, rs174574, rs174575, rs174576, and rs174578 (FADS2) showed significant higher n-6 and n-3 precursor PUFA levels (linoleic acid, and alpha-linolenic acid, respectively) and lower arachidonic acid (AA) levels in erythrocyte membranes compared to the major allele carriers. Differences in EPA and DHA levels were not significant. Minor allele carriers of rs174574, rs174576 and rs174578 (FADS2) and rs174455 (FADS3) exhibited significant higher triglyceride levels, whereas minor allele carriers for rs174449 and rs174455 (FADS3) exhibited significant higher total- and LDL-cholesterol levels compared to the more common variant. The mean omega-3 index of the study cohort was 6.19 ± 1.55 %. In more than 85 % of the patients, the omega-3 index was below 8 % and in 23 % below 5 %. Moreover, it was shown that a low DHA status and omega-3 index was associated with depressive symptoms (Beck's depression-inventory). These findings indicate an
N-3 Polyunsaturated Fatty Acids and Inflammation in Obesity: Local Effect and Systemic Benefit

PubMed Central

Huang, Feiruo

2015-01-01

Overwhelming consensus emerges among countless evidences that obesity is characterized by a chronic low-grade inflammation in the adipose tissue (AT), which subsequently develops into a systemic inflammatory state contributing to obesity-associated diseases. N-3 Polyunsaturated fatty acids (n-3 PUFA), known as important modulators participating in inflammatory process, turn out to be an effective mitigating strategy dealing with local and systemic inflammation observed in obesity. Some of the effects of n-3 PUFA are brought about by regulation of gene expression through interacting with nuclear receptors and transcription factors; other effects are elicited by modulation of the amount and type of mediator derived from PUFAs. The metabolic effects of n-3 PUFA mainly result from their interactions with several organ systems, not limited to AT. Notably, the attenuation of inflammation in hard-hit AT, in turn, contributes to reducing circulating concentrations of proinflammatory cytokines and detrimental metabolic derivatives, which is beneficial for the function of other involved organs. The present review highlights a bridging mechanism between n-3 PUFA-mediated inflammation relief in AT and systemic benefits. PMID:26339623
N-3 Polyunsaturated Fatty Acids and Inflammation in Obesity: Local Effect and Systemic Benefit.

PubMed

Wang, Yue; Huang, Feiruo

2015-01-01

Overwhelming consensus emerges among countless evidences that obesity is characterized by a chronic low-grade inflammation in the adipose tissue (AT), which subsequently develops into a systemic inflammatory state contributing to obesity-associated diseases. N-3 Polyunsaturated fatty acids (n-3 PUFA), known as important modulators participating in inflammatory process, turn out to be an effective mitigating strategy dealing with local and systemic inflammation observed in obesity. Some of the effects of n-3 PUFA are brought about by regulation of gene expression through interacting with nuclear receptors and transcription factors; other effects are elicited by modulation of the amount and type of mediator derived from PUFAs. The metabolic effects of n-3 PUFA mainly result from their interactions with several organ systems, not limited to AT. Notably, the attenuation of inflammation in hard-hit AT, in turn, contributes to reducing circulating concentrations of proinflammatory cytokines and detrimental metabolic derivatives, which is beneficial for the function of other involved organs. The present review highlights a bridging mechanism between n-3 PUFA-mediated inflammation relief in AT and systemic benefits.
Dietary n-3 polyunsaturated fatty acid and status of immunocompetent cells involved in innate immunity in female rats.

PubMed

Sasaki, T; Kanke, Y; Kudoh, K; Nagahashi, M; Toyokawa, M; Matsuda, M; Shimizu, J; Takita, T

2000-01-01

The aim of this study was to estimate the contributions of dietary n-3 polyunsaturated fatty acid (PUFA), a representative dietary immunosuppressant, to the activity of both alveolar macrophages (AM) and natural killer (NK) cells, and compare them to those of n-6 PUFA. Twelve 5-week-old female Sprague-Dawley rats were divided into two dietary groups, one fed a 10% fat diet for 9 weeks enriched with n-3 PUFA (n-3 diet) and the other an n-6 PUFA (n-6 diet). AM reduced the release of nitric oxide, monocyte chemoattractant protein 1 and tumor necrosis factor alpha in the rats fed the n-3 diet, compared with rats fed the n-6 diet. NK cell activity was reduced by consumption of the n-3 diet. This study suggests that consumption of n-3 PUFA can ameliorate pulmonary inflammatory disorders which are affected by the reduction of not only proinflammatory cytokines but also chemokine released from AM. Copyright 2000 S. Karger AG, Basel
Development of rabbit meat products fortified with n-3 polyunsaturated fatty acids.

PubMed

Petracci, Massimiliano; Bianchi, Maurizio; Cavani, Claudio

2009-02-01

Rabbit meat is a highly digestible, tasty, low-calorie food, often recommended by nutritionists over other meats. Currently research in the rabbit sector is interested in developing feeding strategies aiming to further increase the nutritional value of rabbit meat as a "functional food" by including n-3 polyunsaturated fatty acids (n-3 PUFA), conjugated linoleic acid (CLA), vitamins and antioxidants in rabbit diets and assessing their effects on both raw and stored/processed meat quality properties. Our recent studies indicate that the dietary inclusion from 3 to 6% of linseed might be considered as a way to achieve the enrichment of the meat with α-linolenic acid and to guarantee satisfactory product stability during further processing and storage. Considering that 6% dietary linseed corresponds to a n-3 PUFA content of 8.5% of the total fatty acids and a lipid content of 4.7 g/100 g of leg meat, a content of 396 mg n-3 PUFA/100g meat can be estimated, which represents about 19% of the recommended daily allowance (RDA) for n-3 PUFA.
Development of Rabbit Meat Products Fortified With n-3 Polyunsaturated Fatty Acids

PubMed Central

Petracci, Massimiliano; Bianchi, Maurizio; Cavani, Claudio

2009-01-01

Rabbit meat is a highly digestible, tasty, low-calorie food, often recommended by nutritionists over other meats. Currently research in the rabbit sector is interested in developing feeding strategies aiming to further increase the nutritional value of rabbit meat as a “functional food” by including n-3 polyunsaturated fatty acids (n-3 PUFA), conjugated linoleic acid (CLA), vitamins and antioxidants in rabbit diets and assessing their effects on both raw and stored/processed meat quality properties. Our recent studies indicate that the dietary inclusion from 3 to 6% of linseed might be considered as a way to achieve the enrichment of the meat with α-linolenic acid and to guarantee satisfactory product stability during further processing and storage. Considering that 6% dietary linseed corresponds to a n-3 PUFA content of 8.5% of the total fatty acids and a lipid content of 4.7 g/100 g of leg meat, a content of 396 mg n-3 PUFA/100g meat can be estimated, which represents about 19% of the recommended daily allowance (RDA) for n-3 PUFA. PMID:22253971
Intentions to consume omega-3 fatty acids: a comparison of protection motivation theory and ordered protection motivation theory.

PubMed

Calder, Samuel Christian; Davidson, Graham R; Ho, Robert

2011-06-01

There has been limited research to date into methods for increasing people's intentions to use omega-3 polyunsaturated fatty acids (n-3 PUFA), which have been linked with decreased risk of suffering from numerous major diseases. The present study employed a cross-sectional design with 380 university students, employees, and visitors to investigate the efficacy of the protection motivation (PM) theory and the ordered protection motivation (OPM) theory, to predict behavioral intention to consume omega-3 rich foods and dietary supplements. Analysis of model fit indicated that both the PM model and the OPM model adequately represented the structural relationships between the cognitive variables and intention to consume n-3 PUFA. Further evaluation of relative fit of the two competing models suggested that the PM model might provide a better representation of decision-making following evaluation of the health threat of n-3 PUFA deficiency. Path analysis indicated that the component of coping appraisal was significantly associated with the behavioral intention to consume n-3 PUFA. Threat appraisal was found to be significantly associated with behavioral intention to consume n-3 PUFA only for the OPM model. Overall, the findings contribute to a better understanding of the roles that cognitive appraisal processes play in young and healthy individuals' protective health decision-making regarding consumption of n-3 PUFA. Implications of the findings and recommendations, which include (a) encouraging the consumption of n-3 PUFA as an effective barrier against the incidence of disease, and (b) effective health messaging that focuses on beliefs about the effectiveness of n-3 PUFA in reducing health risks, are discussed.
Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats with Reflux Esophagitis.

PubMed

Zhuang, Jia-Yuan; Chen, Zhi-Yao; Zhang, Tao; Tang, Du-Peng; Jiang, Xiao-Yin; Zhuang, Ze-Hao

2017-01-30

BACKGROUND We designed this study to investigate the influence of different ratios of n-6/n-3 polyunsaturated fatty acid in the diet of reflux esophagitis (RE) rats' and the effect on the PI3K/Akt pathway. MATERIAL AND METHODS RE rats were randomly divided into a sham group and modeling groups of different concentrations of n-6/n-3 polyunsaturated fatty acid (PUFA): 12:1 group, 10:1 group, 5:1 group, and 1:1 group. RT-PCR and Western-blot were used to detect the expression of PI3K, Akt, p-Akt, NF-κBp50, and NF-κBp65 proteins in esophageal tissue. RESULTS In the n-6/n-3 PUFAs groups the expression of PI3K, Akt, p-Akt, nf-κbp50, and NF-κBp65 mRNA decreased with the decrease in n-6/n-3 ratios in the diet. The lowest expression of each indicator occurred in the 1:1 n-6/n-3 group compared with other n-6/n-3 groups, the difference was statistically significant (p<0.05). CONCLUSIONS The inhibition of n-3 PUFAs in the development of esophageal inflammation in rats with RE was attributed to the function of PI3K/Akt-NF-κB signaling pathway.
N-3 polyunsaturated fatty acids intake and risk of colorectal cancer: meta-analysis of prospective studies.

PubMed

Chen, Guo-Chong; Qin, Li-Qiang; Lu, Da-Bing; Han, Tie-Mei; Zheng, Yan; Xu, Guo-Zhang; Wang, Xiao-Huai

2015-01-01

Growing body of laboratory evidence supports the beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC) prevention. Epidemiologic studies investigating the relationship between n-3 PUFAs intake and risk of CRC, however, have been inconsistent. We aimed to clarify the relation by conducting a meta-analysis of prospective studies. Eligible studies were identified by searching PubMed database and by carefully reviewing bibliographies of retrieved publications. Summary relative risks (RRs) with their 95 % confidence intervals (CIs) were computed with a random-effects model. Subgroup, meta-regression, and dose-response analyses were performed to explore potential sources of heterogeneity. A total of 14 prospective studies involving 8,775 cancer cases were included in the final analysis. Overall, total n-3 or marine PUFAs intake was not associated with risk of CRC (RR 0.99 and 1.00). However, there was a trend toward reduced risk of proximal colon cancer (total n-3 PUFAs: RR 0.83, 95 % CI 0.66-1.05; marine PUFAs: RR 0.81, 95 % CI 0.59-1.10) and a significant increased risk of distal colon cancer (total n-3 PUFAs: RR 1.26, 95 % CI 1.06-1.50; marine PUFAs: RR 1.38, 95 % CI 1.11-1.71). Furthermore, marine PUFAs intake accessed longer before diagnosis was associated 21 % reduced risk of CRC (RR 0.79, 95 % CI 0.63-1.00). Overall, this meta-analysis finds no relation between n-3 PUFAs intake and risk of CRC. The observed subsite heterogeneity within colon cancer and the possible effect modification by latency time merit further studies.

Maternal PUFA status but not prenatal methylmercury exposure is associated with children's language functions at age five years in the Seychelles.

PubMed

Strain, J J; Davidson, Philip W; Thurston, Sally W; Harrington, Donald; Mulhern, Maria S; McAfee, Alison J; van Wijngaarden, Edwin; Shamlaye, Conrad F; Henderson, Juliette; Watson, Gene E; Zareba, Grazyna; Cory-Slechta, Deborah A; Lynch, Miranda; Wallace, Julie M W; McSorley, Emeir M; Bonham, Maxine P; Stokes-Riner, Abbie; Sloane-Reeves, Jean; Janciuras, Joanne; Wong, Rosa; Clarkson, Thomas W; Myers, Gary J

2012-11-01

Evidence from the Seychelles Child Development Nutrition Study suggests that maternal nutritional status can modulate the relationship between prenatal methylmercury (MeHg) exposure and developmental outcomes in children. The aim of this study was to investigate whether maternal PUFA status was a confounding factor in any possible associations between prenatal MeHg exposure and developmental outcomes at 5 y of age in the Republic of Seychelles. Maternal status of (n-3) and (n-6) PUFA were measured in serum collected at 28 wk gestation and delivery. Prenatal MeHg exposure was determined in maternal hair collected at delivery. At 5 y of age, the children completed a comprehensive range of sensitive developmental assessments. Complete data from 225 mothers and their children were available for analysis. Multiple linear regression analyses revealed Preschool Language Scale scores of the children improved with increasing maternal serum DHA [22:6(n-3)] concentrations and decreased with increasing arachidonic acid [20:4(n-6)] concentrations, albeit verbal intelligence improved with increasing (n-6) PUFA concentrations in maternal serum. There were no adverse associations between MeHg exposure and developmental outcomes. These findings suggest that higher fish consumption, resulting in higher maternal (n-3) PUFA status, during pregnancy is associated with beneficial developmental effects rather than detrimental effects resulting from the higher concomitant exposures of the fetus to MeHg. The association of maternal (n-3) PUFA status with improved child language development may partially explain the authors' previous finding of improving language scores, as prenatal MeHg exposure increased in an earlier mother-child cohort in the Seychelles where maternal PUFA status was not measured.
Effects of baked and raw salmon fillet on lipids and n-3 PUFAs in serum and tissues in Zucker fa/fa rats.

PubMed

Vikøren, Linn A; Drotningsvik, Aslaug; Bergseth, Marthe T; Mjøs, Svein A; Mola, Nazanin; Leh, Sabine; Mellgren, Gunnar; Gudbrandsen, Oddrun A

2017-01-01

Knowledge of the health impact of consuming heat-treated versus raw fish fillet is limited. To investigate effects of baked or raw salmon fillet intake on lipids and n-3 PUFAs in serum and tissues, obese Zucker fa/fa rats were fed diets containing 25% of protein from baked or raw salmon fillet and 75% of protein from casein, or casein as the sole protein source (control group) for four weeks. Salmon diets had similar composition of amino and fatty acids. Growth and energy intake were similar in all groups. Amounts of lipids and n-3 PUFAs in serum, liver and skeletal muscle were similar between rats fed baked or raw salmon fillet. When compared to the control group, rats fed baked salmon had lower serum total and LDL cholesterol and higher serum triacylglycerol levels. Both raw and baked salmon groups had lower HDL cholesterol level when compared to control rats. In conclusion, baking as a preparation method does not alter protein and fat qualities of salmon fillets, and intake of baked and raw salmon fillets gave similar effects on lipids and n-3 PUFAs in serum and tissues from rats.
Effects of baked and raw salmon fillet on lipids and n-3 PUFAs in serum and tissues in Zucker fa/fa rats

PubMed Central

Vikøren, Linn A.; Drotningsvik, Aslaug; Bergseth, Marthe T.; Mjøs, Svein A.; Mola, Nazanin; Leh, Sabine; Mellgren, Gunnar; Gudbrandsen, Oddrun A.

2017-01-01

ABSTRACT Knowledge of the health impact of consuming heat-treated versus raw fish fillet is limited. To investigate effects of baked or raw salmon fillet intake on lipids and n-3 PUFAs in serum and tissues, obese Zucker fa/fa rats were fed diets containing 25% of protein from baked or raw salmon fillet and 75% of protein from casein, or casein as the sole protein source (control group) for four weeks. Salmon diets had similar composition of amino and fatty acids. Growth and energy intake were similar in all groups. Amounts of lipids and n-3 PUFAs in serum, liver and skeletal muscle were similar between rats fed baked or raw salmon fillet. When compared to the control group, rats fed baked salmon had lower serum total and LDL cholesterol and higher serum triacylglycerol levels. Both raw and baked salmon groups had lower HDL cholesterol level when compared to control rats. In conclusion, baking as a preparation method does not alter protein and fat qualities of salmon fillets, and intake of baked and raw salmon fillets gave similar effects on lipids and n-3 PUFAs in serum and tissues from rats. PMID:28659746
N-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth.

PubMed

Cao, Wenqing; Ma, ZhiFan; Rasenick, Mark M; Yeh, ShuYan; Yu, JiangZhou

2012-01-01

Although evidence has shown the regulating effect of n-3 poly-unsaturated fatty acid (n-3 PUFA) on cell signaling transduction, it remains unknown whether n-3 PUFA treatment modulates estrogen signaling. The current study showed that docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) shifted the pro-survival and proliferative effect of estrogen to a pro-apoptotic effect in human breast cancer (BCa) MCF-7 and T47D cells. 17 β-estradiol (E2) enhanced the inhibitory effect of n-3 PUFAs on BCa cell growth. The IC50 of DHA or EPA in MCF-7 cells decreased when combined with E2 (10 nM) treatment (from 173 µM for DHA only to 113 µM for DHA+E2, and from 187 µm for EPA only to 130 µm for EPA+E2). E2 also augmented apoptosis in n-3 PUFA-treated BCa cells. In contrast, in cells treated with stearic acid (SA, C18:0) as well as cells not treated with fatty acid, E2 promoted breast cancer cell growth. Classical (nuclear) estrogen receptors may not be involved in the pro-apoptotic effects of E2 on the n-3 PUFA-treated BCa cells because ERα agonist failed to elicit, and ERα knockdown failed to block E2 pro-apoptotic effects. Subsequent studies reveal that G protein coupled estrogen receptor 1 (GPER1) may mediate the pro-apoptotic effect of estrogen. N-3 PUFA treatment initiated the pro-apoptotic signaling of estrogen by increasing GPER1-cAMP-PKA signaling response, and blunting EGFR, Erk 1/2, and AKT activity. These findings may not only provide the evidence to link n-3 PUFAs biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, but also shed new insight into the potential application of n-3 PUFAs in BCa treatment.
N-3 polyunsaturated fatty acids and 17β-estradiol injection induce antidepressant-like effects through regulation of serotonergic neurotransmission in ovariectomized rats.

PubMed

Jin, Youri; Park, Yongsoon

2015-09-01

Previous studies have suggested that estrogen and n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antidepressant-like effects. The purpose of the present study was to determine the interaction between n-3 PUFAs and estrogen, and their neurotrophic mechanism in rats after the forced swimming test (FST). Rats were fed a modified American Institute of Nutrition 93G diet with 0%, 1% or 2% EPA+DHA relative to the total energy intake during 12 weeks. At 8 weeks, rats were ovariectomized and injected with either 17β-estradiol-3-benzoate (E2) or corn oil during the last 3 weeks. Both n-3 PUFA supplementation and E2 injection increased climbing and decreased immobility during the FST. Serum serotonin concentration was also increased by both n-3 PUFA and E2. N-3 PUFA and E2 decreased hippocampal expressions of interleukin (IL)-6 and tumor necrosis factor-α, and increased cAMP response element binding protein (CREB), phosphorylated CREB and brain-derived neurotrophic factor (BDNF). N-3 PUFA supplementation decreased hippocampal expression of IL-1β only in rats injected with E2. Both n-3 PUFA supplementation and E2 injection increased estrogen receptor (ER)-α in the hippocampus, but ER-β was increased only by E2 injection. Additionally, there was a significant interaction between n-3 PUFA supplementation and E2 injection on the hippocampal expression of pCREB, suggesting membrane-mediated interaction of n-3 PUFAs and E2. In conclusion, both n-3 PUFA and E2 had antidepressant-like effects by regulating serotonergic neurotransmission through BDNF and inflammatory cytokines. Copyright © 2015 Elsevier Inc. All rights reserved.
Polymorphisms in Fatty Acid Desaturase (FADS) Gene Cluster: Effects on Glycemic Controls Following an Omega-3 Polyunsaturated Fatty Acids (PUFA) Supplementation.

PubMed

Cormier, Hubert; Rudkowska, Iwona; Thifault, Elisabeth; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2013-09-10

Changes in desaturase activity are associated with insulin sensitivity and may be associated with type 2 diabetes mellitus (T2DM). Polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster have been associated with the homeostasis model assessment of insulin sensitivity (HOMA-IS) and serum fatty acid composition. To investigate whether common genetic variations in the FADS gene cluster influence fasting glucose (FG) and fasting insulin (FI) responses following a 6-week n-3 polyunsaturated fatty acids (PUFA) supplementation. 210 subjects completed a 2-week run-in period followed by a 6-week supplementation with 5 g/d of fish oil (providing 1.9 g-2.2 g of EPA + 1.1 g of DHA). Genotyping of 18 SNPs of the FADS gene cluster covering 90% of all common genetic variations (minor allele frequency ≥ 0.03) was performed. Carriers of the minor allele for rs482548 (FADS2) had increased plasma FG levels after the n-3 PUFA supplementation in a model adjusted for FG levels at baseline, age, sex, and BMI. A significant genotype*supplementation interaction effect on FG levels was observed for rs482548 (p = 0.008). For FI levels, a genotype effect was observed with one SNP (rs174456). For HOMA-IS, several genotype*supplementation interaction effects were observed for rs7394871, rs174602, rs174570, rs7482316 and rs482548 (p = 0.03, p = 0.01, p = 0.03, p = 0.05 and p = 0.07; respectively). RESULTS suggest that SNPs in the FADS gene cluster may modulate plasma FG, FI and HOMA-IS levels in response to n-3 PUFA supplementation.
Polymorphisms in Fatty Acid Desaturase (FADS) Gene Cluster: Effects on Glycemic Controls Following an Omega-3 Polyunsaturated Fatty Acids (PUFA) Supplementation

PubMed Central

Cormier, Hubert; Rudkowska, Iwona; Thifault, Elisabeth; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2013-01-01

Changes in desaturase activity are associated with insulin sensitivity and may be associated with type 2 diabetes mellitus (T2DM). Polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster have been associated with the homeostasis model assessment of insulin sensitivity (HOMA-IS) and serum fatty acid composition. Objective: To investigate whether common genetic variations in the FADS gene cluster influence fasting glucose (FG) and fasting insulin (FI) responses following a 6-week n-3 polyunsaturated fatty acids (PUFA) supplementation. Methods: 210 subjects completed a 2-week run-in period followed by a 6-week supplementation with 5 g/d of fish oil (providing 1.9 g–2.2 g of EPA + 1.1 g of DHA). Genotyping of 18 SNPs of the FADS gene cluster covering 90% of all common genetic variations (minor allele frequency ≥ 0.03) was performed. Results: Carriers of the minor allele for rs482548 (FADS2) had increased plasma FG levels after the n-3 PUFA supplementation in a model adjusted for FG levels at baseline, age, sex, and BMI. A significant genotype*supplementation interaction effect on FG levels was observed for rs482548 (p = 0.008). For FI levels, a genotype effect was observed with one SNP (rs174456). For HOMA-IS, several genotype*supplementation interaction effects were observed for rs7394871, rs174602, rs174570, rs7482316 and rs482548 (p = 0.03, p = 0.01, p = 0.03, p = 0.05 and p = 0.07; respectively). Conclusion: Results suggest that SNPs in the FADS gene cluster may modulate plasma FG, FI and HOMA-IS levels in response to n-3 PUFA supplementation. PMID:24705214
Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs12

PubMed Central

Gabbs, Melissa; Leng, Shan; Devassy, Jessay G; Monirujjaman, Md; Aukema, Harold M

2015-01-01

Oxylipins formed from polyunsaturated fatty acids (PUFAs) are the main mediators of PUFA effects in the body. They are formed via cyclooxygenase, lipoxygenase, and cytochrome P450 pathways, resulting in the formation of prostaglandins, thromboxanes, mono-, di-, and tri-hydroxy fatty acids (FAs), epoxy FAs, lipoxins, eoxins, hepoxilins, resolvins, protectins (also called neuroprotectins in the brain), and maresins. In addition to the well-known eicosanoids derived from arachidonic acid, recent developments in lipidomic methodologies have raised awareness of and interest in the large number of oxylipins formed from other PUFAs, including those from the essential FAs and the longer-chain n–3 (ω-3) PUFAs. Oxylipins have essential roles in normal physiology and function, but can also have detrimental effects. Compared with the oxylipins derived from n–3 PUFAs, oxylipins from n–6 PUFAs generally have greater activity and more inflammatory, vasoconstrictory, and proliferative effects, although there are notable exceptions. Because PUFA composition does not necessarily reflect oxylipin composition, comprehensive analysis of the oxylipin profile is necessary to understand the overall physiologic effects of PUFAs mediated through their oxylipins. These analyses should include oxylipins derived from linoleic and α-linolenic acids, because these largely unexplored bioactive oxylipins constitute more than one-half of oxylipins present in tissues. Because collated information on oxylipins formed from different PUFAs is currently unavailable, this review provides a detailed compilation of the main oxylipins formed from PUFAs and describes their functions. Much remains to be elucidated in this emerging field, including the discovery of more oxylipins, and the understanding of the differing biological potencies, kinetics, and isomer-specific activities of these novel PUFA metabolites. PMID:26374175
The effect of n-3/n-6 polyunsaturated fatty acids on acute reflux esophagitis in rats.

PubMed

Zhuang, Ze-Hao; Xie, Jing-Jing; Wei, Jing-Jing; Tang, Du-Peng; Yang, Li-Yong

2016-10-04

Polyunsaturated fatty acids (PUFAs) play various roles in inflammation. However, the effect of PUFAs in the development of reflux esophagitis (RE) is unclear. This study is to investigate the potential effect of n-3/n-6 PUFAs on acute RE in rats along with the underlying protective mechanisms. Forty Sprague Dawley rats were randomly divided into four groups (n = 10 in each group). RE model was established by pyloric clip and section ligation. Fish oil- and soybean oil-based fatty emulsion (n-3 and n-6 groups), or normal saline (control and sham operation groups) was injected intraperitoneally 2 h prior to surgery and 24 h postoperatively (2 mL/kg, respectively). The expressions of interleukin (IL)-1β, IL-8, IL-6 and myeloid differentiation primary response gene 88 (MyD88) in esophageal tissues were evaluated by Western blot and immunohistochemistry after 72 h. The malondialdehyde (MDA) and superoxide dismutase (SOD) expression in the esophageal tissues were determined to assess the oxidative stress. The mildest macroscopic/microscopic esophagitis was found in the n-3 group (P < 0.05). The expression of IL-1β, IL-8, IL-6 and MyD88 were increased in all RE groups, while the lowest and highest expression were found in n-3 and n-6 group, respectively (P < 0.05). The MDA levels were increased in all groups (P < 0.05), in an ascending trend from n-3, n-6 groups to control group. The lowest and highest SOD levels were found in the control and n-3 group, respectively (P < 0.05). n-3 PUFAs may reduce acute RE in rats, which may be due to inhibition of the MyD88-NF-kB pathway and limit oxidative damage.
Acetaminophen-induced liver injury is attenuated in transgenic fat-1 mice endogenously synthesizing long-chain n-3 fatty acids.

PubMed

Feng, Ruibing; Wang, Yang; Liu, Conghui; Yan, Chunyan; Zhang, Hang; Su, Huanxing; Kang, Jing X; Shang, Chang-Zhen; Wan, Jian-Bo

2018-04-18

Acetaminophen (APAP) overdose-induced hepatotoxicity is the most commonly cause of drug-induced liver failure characterized by oxidative stress, mitochondrial dysfunction, and cell damage. Therapeutic efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFA) in several models of liver disease is well documented. However, the impacts of n-3 PUFA on APAP hepatotoxicity are not adequately addressed. In this study, the fat-1 transgenic mice that synthesize endogenous n-3 PUFA and wild type (WT) littermates were injected intraperitoneally with APAP at the dose of 400 mg/kg to induce liver injury, and euthanized at 0 h, 2 h, 4 h and 6 h post APAP injection for sampling. APAP overdose caused severe liver injury in WT mice as indicated by serum parameters, histopathological changes and hepatocyte apoptosis, which were remarkably ameliorated in fat-1 mice. These protective effects of n-3 PUFA were associated with regulation of the prolonged JNK activation via inhibition of apoptosis signal-regulating kinase 1 (ASK1)/mitogen-activated protein kinase kinase 4 (MKK4) pathway. Additionally, the augment of endogenous n-3 PUFA reduced nuclear factor kappa B (NF-κB) - mediated inflammation response induced by APAP treatment in the liver. These findings indicate that n-3 PUFA has potent protective effects against APAP-induced acute liver injury, suggesting that n-3 dietary supplement with n-3 PUFA may be a potential therapeutic strategy for the treatment of hepatotoxicity induced by APAP overdose. Copyright © 2018 Elsevier Inc. All rights reserved.
Dietary n-3 polyunsaturated fatty acid intake and all-cause and cardiovascular mortality in adults on hemodialysis: The DIET-HD multinational cohort study.

PubMed

Saglimbene, Valeria M; Wong, Germaine; Ruospo, Marinella; Palmer, Suetonia C; Campbell, Katrina; Larsen, Vanessa Garcia; Natale, Patrizia; Teixeira-Pinto, Armando; Carrero, Juan-Jesus; Stenvinkel, Peter; Gargano, Letizia; Murgo, Angelo M; Johnson, David W; Tonelli, Marcello; Gelfman, Rubén; Celia, Eduardo; Ecder, Tevfik; Bernat, Amparo G; Del Castillo, Domingo; Timofte, Delia; Török, Marietta; Bednarek-Skublewska, Anna; Duława, Jan; Stroumza, Paul; Hoischen, Susanne; Hansis, Martin; Fabricius, Elisabeth; Wollheim, Charlotta; Hegbrant, Jörgen; Craig, Jonathan C; Strippoli, Giovanni F M

2017-12-06

Patients on hemodialysis suffer from high risk of premature death, which is largely attributed to cardiovascular disease, but interventions targeting traditional cardiovascular risk factors have made little or no difference. Long chain n-3 polyunsaturated fatty acids (n-3 PUFA) are putative candidates to reduce cardiovascular disease. Diets rich in n-3 PUFA are recommended in the general population, although their role in the hemodialysis setting is uncertain. We evaluated the association between the dietary intake of n-3 PUFA and mortality for hemodialysis patients. The DIET-HD study is a prospective cohort study (January 2014-June 2017) in 9757 adults treated with hemodialysis in Europe and South America. Dietary n-3 PUFA intake was measured at baseline using the GA 2 LEN Food Frequency Questionnaire. Adjusted Cox regression analyses clustered by country were conducted to evaluate the association of dietary n-3 PUFA intake with cardiovascular and all-cause mortality. During a median follow up of 2.7 years (18,666 person-years), 2087 deaths were recorded, including 829 attributable to cardiovascular causes. One third of the study participants consumed sufficient (at least 1.75 g/week) n-3 PUFA recommended for primary cardiovascular prevention, and less than 10% recommended for secondary prevention (7-14 g/week). Compared to patients with the lowest tertile of dietary n-3 PUFA intake (<0.37 g/week), the adjusted hazard ratios (95% confidence interval) for cardiovascular mortality for patients in the middle (0.37 to <1.8 g/week) and highest (≥1.8 g/week) tertiles of n-3 PUFA were 0.82 (0.69-0.98) and 1.03 (0.84-1.26), respectively. Corresponding adjusted hazard ratios for all-cause mortality were 0.96 (0.86-1.08) and 1.00 (0.88-1.13), respectively. Dietary n-3 PUFA intake was not associated with cardiovascular or all-cause mortality in patients on hemodialysis. As dietary n-3 PUFA intake was low, the possibility that n-3 PUFA supplementation might mitigate
Low breast milk levels of long-chain n-3 fatty acids in allergic women, despite frequent fish intake.

PubMed

Johansson, S; Wold, A E; Sandberg, A-S

2011-04-01

Long-chain n-3 polyunsaturated fatty acids (PUFAs) have immune regulating and anti-inflammatory effects. However, their role in allergic disease is unclear. Allergic diseases are immunologically heterogeneous, and we hypothesized that n-3 fatty acid composition in serum and breast milk may vary according to clinical manifestations. Further, animal studies have shown reduction of serum-PUFA levels during allergic inflammation. To investigate fatty acid composition in breast milk and serum from women with different atopic disease manifestations. Secondly, to determine whether low PUFA levels reflected insufficient intakes. Fatty acids were analysed in breast milk and serum of women with atopic eczema and respiratory allergy (n=16), only respiratory allergy (n=7), as well as healthy women (n=22). Dietary intake of foods expected to affect long-chain n-3 PUFA levels were estimated by food-frequency questionnaire. The fatty acid pattern was related to diagnostic group and intake of relevant food items using a multivariate pattern recognition method (partial least squares projections to latent structures and discriminant analysis). Results Women with a combination of eczema and respiratory allergy had lower breast milk levels of several PUFAs (arachidonic acid, eicosapentaenoic acid, EPA, docosahexaenoic acid, DHA, and docosapentaenoic acid, DPA), and a lower ratio of long-chain n-3 PUFAs/n-6 PUFAs. Their PUFA levels differed not only from that of healthy women, but also from that of women with only respiratory allergy. The latter had a fatty acid pattern similar to that of healthy women. Despite low EPA, DHA and DPA levels women with eczema and respiratory allergy consumed no less fish than did healthy women. Our data suggest that reduced levels of long-chain n-3 fatty acids in serum and breast milk characterize women with extensive allergic disease including eczema, and are not related to low fish intake. Consumption of PUFAs during the allergic process may explain
Effects of Chinese Dietary Pattern of Fat Content, n-6/n-3 Polyunsaturated Fatty Acid Ratio, and Cholesterol Content on Lipid Profile in Rats

PubMed Central

Zou, Xian-Guo; Huang, Yu-Hua; Xu, Tong-Cheng; Fan, Ya-Wei; Li, Jing

2018-01-01

This study aims to investigate the effect of Chinese diet pattern of fat content (30% or 36.06%), n-6/n-3 polyunsaturated fatty acid (PUFA) ratio (5 : 1 or 9 : 1), and cholesterol content (0.04 or 0.057 g/kg total diet) on lipid profile using a rat model. Results showed that rats' body weights (BWs) were controlled by the simultaneous intakes of cholesterol level of 0.04 g/kg total diet and n-6/n-3 ratio of 5 : 1. In addition, under high-fat diet, increased cholesterol feeding led to increased total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels and decreased triacylglycerols (TG) in rats' plasma. However, high density lipoprotein cholesterol (HDL-C) level and the ratios of HDL-C/LDL-C and HDL-C/TC in rats' plasma increased in response to simultaneous intakes of low n-6/n-3 ratio (5 : 1) and cholesterol (0.04 g/kg total diet) even under high-fat diet. Moreover, as the n-6/n-3 PUFA ratio in the diet decreased, the proportion of n-3 PUFAs increased in plasma, liver, and muscle and resulted in the decrease of n-6/n-3 PUFA ratio. PMID:29744358
Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.

PubMed

Tan, May Loong; Ho, Jacqueline J; Teh, Keng Hwang

2016-09-28

About 5% of school children have a specific learning disorder, defined as unexpected failure to acquire adequate abilities in reading, writing or mathematics that is not a result of reduced intellectual ability, inadequate teaching or social deprivation. Of these events, 80% are reading disorders. Polyunsaturated fatty acids (PUFAs), in particular, omega-3 and omega-6 fatty acids, which normally are abundant in the brain and in the retina, are important for learning. Some children with specific learning disorders have been found to be deficient in these PUFAs, and it is argued that supplementation of PUFAs may help these children improve their learning abilities. 1. To assess effects on learning outcomes of supplementation of polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.2. To determine whether adverse effects of supplementation of PUFAs are reported in these children. In November 2015, we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, 10 other databases and two trials registers. We also searched the reference lists of relevant articles. Randomised controlled trials (RCTs) or quasi-RCTs comparing PUFAs with placebo or no treatment in children younger than 18 years with specific learning disabilities, as diagnosed in accordance with the fifth (or earlier) edition of theDiagnostic and Statistical Manual of Mental Disorders (DSM-5), or the 10th (or earlier) revision of the International Classification of Diseases (ICD-10) or equivalent criteria. We included children with coexisting developmental disorders such as attention deficit hyperactivity disorder (ADHD) or autism. Two review authors (MLT and KHT) independently screened the titles and abstracts of articles identified by the search and eliminated all studies that did not meet the inclusion criteria. We contacted study authors to ask for missing information and clarification, when needed. We used the GRADE approach to assess the quality of evidence. Two small studies
Mead acid (20:3n-9) and n-3 polyunsaturated fatty acids are not associated with risk of posterior longitudinal ligament ossification: results of a case-control study.

PubMed

Hamazaki, Kei; Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Seki, Shoji; Hori, Takeshi; Hamazaki, Tomohito; Kimura, Tomoatsu

2015-05-01

Ossification of the posterior longitudinal ligament (OPLL) involves the replacement of ligamentous tissue with ectopic bone. Although genetics and heritability appear to be involved in the development of OPLL, its pathogenesis remains to be elucidated. Given previous findings that 5,8,11-eicosatrienoic acid [20:3n-9, Mead acid (MA)] has depressive effects on osteoblastic activity and anti-angiogenic effects, and that n-3 polyunsaturated fatty acids (PUFAs) have a preventive effect on heterotopic ossification, we hypothesized that both fatty acids would be involved in OPLL development. To examine the biological significance of these and other fatty acids in OPLL, we conducted this case-control study involving 106 patients with cervical OPLL and 109 age matched controls. Fatty acid composition was determined from plasma samples by gas chromatography. Associations between fatty acid levels and incident OPLL were evaluated by logistic regression. Contrary to our expectations, we found no significant differences between patients and controls in the levels of MA or n-3 PUFAs (e.g., eicosapentaenoic acid and docosahexaenoic acid). Logistic regression analysis did not reveal any associations with OPLL risk for MA or n-3 PUFAs. In conclusion, no potential role was found for MA or n-3 PUFAs in ectopic bone formation in the spinal canal. Copyright © 2015 Elsevier Ltd. All rights reserved.
Mind-body interface: the role of n-3 fatty acids in psychoneuroimmunology, somatic presentation, and medical illness comorbidity of depression.

PubMed

Su, Kuan-Pin

2008-01-01

With the unsatisfaction of monoamine-based pharmacotherapy and the high comorbidity of other medical illness in depression, the serotonin hypothesis seems to fail in approaching the aetiology of depression. Based upon the evidence from epidemiological data, case-control studies of phospholipid polyunsaturated fatty acids (PUFAs) levels in human tissues, and antidepressant effect in clinical trials, PUFAs have shed a light to discover the unsolved of depression and connect the mind and body. Briefly, the deficit of n-3 PUFAs has been reported to be associated with neurological, cardiovascular, cerebrovascular, autoimmune, metabolic diseases and cancers. Recent studies revealed that the deficit of n-3 PUFAs is also associated with depression. For example, societies that consume a small amount of omega-3 PUFAs appear to have a higher prevalence of major depressive disorder. In addition, depressive patients had showed a lower level of omega-3 PUFAs; and the antidepressant effect of PUFAs had been reported in a number of clinical trials. The PUFAs are classified into n-3 (or omega-3) and n-6 (or omega-6) groups. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the major bioactive components of n-3 PUFAs, are not synthesized in human body and can only be obtained directly from the diet, particularly by consuming fish. DHA deficit is associated with dysfunctions of neuronal membrane stability and transmission of serotonin, norepinephrine and dopamine, which might connect to the aetiology of mood and cognitive dysfunction of depression. On the other hand, EPA is important in balancing the immune function and physical healthy by reducing arachidonic acid (AA, an n-6 PUFA) level on cell membrane and prostaglandin E2 (PGE2) synthesis. Interestingly, animals fed with high AA diet or treated with PGE2 were observed to present sickness behaviours of anorexia, low activity, change in sleep pattern and attention, which are similar to somatic symptoms of depression in
Higher n3-fatty acid status is associated with lower risk of iron depletion among food insecure Canadian Inuit women.

PubMed

Jamieson, Jennifer A; Kuhnlein, Harriet V; Weiler, Hope A; Egeland, Grace M

2013-04-02

High rates of iron deficiency and anemia are common among Inuit and Arctic women despite a traditional diet based on animal source foods. However, representative data on iron status and relevant determinants for this population are lacking. The objectives were to determine the prevalence of anemia and depletion of iron stores, then to identify correlates of iron status in non-pregnant Canadian Inuit women. In a cross-sectional survey of 1550 women in the International Polar Year Inuit Health Survey, 2007-2008, hemoglobin, serum ferritin, soluble transferrin receptor (on a subset), C-reactive protein (CRP), RBC fatty acid composition, and H pylori serology were analyzed on fasting venous blood. Sociodemographic, food security status, anthropometric, dietary, and health data were collected. Correlates of iron status were assessed with multivariate linear and logistic models. Anemia was observed in 21.7% and iron deficient erythropoiesis in 3.3% of women. For women with CRP ≤ 10 mg/L (n = 1260) 29.4% had depleted iron stores. Inadequate iron intakes were observed in 16% of premenopausal and <1% of postmenopausal women. Among food insecure women, higher long-chain (n-3) polyunsaturated fatty acid (LC-PUFA) status, which reflects a more traditional food pattern, was associated with reduced risk of iron depletion. Iron depletion and anemia are a concern for Inuit women despite adequate total dietary iron intake primarily from heme sources. The high prevalence of H. pylori exposure, together with dietary iron adequacy, suggests an inflammation-driven iron deficiency and mild anemia. The anti-inflammatory properties of LC-PUFA may be important for iron status in this population.
Dietary n-3 polyunsaturated fatty acids affect the development of renovascular hypertension in rats

NASA Technical Reports Server (NTRS)

Rousseau, D.; Helies-Toussaint, C.; Raederstorff, D.; Moreau, D.; Grynberg, A.

2001-01-01

The consequences of a dietary n-3 PUFA supply was investigated on the blood pressure (BP) increase elicited by left renal artery stenosis in rats distributed in 3 groups (n = 8) fed for 8 weeks a semi-purified diet either as control diet or enriched diets (docosahexaenoic acid, DHA, or eicosapentaenoic acid, EPA). The PUFA intake induced large alterations in heart and kidney phospholipid fatty acid profile, but did not influence body weight, cardiac hypertrophy, renal left atrophy and right hypertrophy. Within 4 weeks, BP raised from 120-180 +/- 2 mm Hg in the control group, but only to 165 +/- 3 mm Hg in the n-3 PUFA groups. After stabilization of BP in the 3 groups, the rats received a short administration of increasing dose of perindopril. The lower dose (0.5 mg/kg) moderately decreased BP only in the control group. With higher doses (1, 5 and 10 mg/kg) BP was normalized in the 3 groups, with a higher amplitude of the BP lowering effect in the control group. A moderate n-3 PUFA intake can contribute to prevent the development of peripheral hypertension in rats by a mechanism that may involve angiotensin converting enzyme.
Dietary n-3 polyunsaturated fatty acids affect the development of renovascular hypertension in rats.

PubMed

Rousseau, D; Héliès-Toussaint, C; Raederstorff, D; Moreau, D; Grynberg, A

2001-09-01

The consequences of a dietary n-3 PUFA supply was investigated on the blood pressure (BP) increase elicited by left renal artery stenosis in rats distributed in 3 groups (n = 8) fed for 8 weeks a semi-purified diet either as control diet or enriched diets (docosahexaenoic acid, DHA, or eicosapentaenoic acid, EPA). The PUFA intake induced large alterations in heart and kidney phospholipid fatty acid profile, but did not influence body weight, cardiac hypertrophy, renal left atrophy and right hypertrophy. Within 4 weeks, BP raised from 120-180 +/- 2 mm Hg in the control group, but only to 165 +/- 3 mm Hg in the n-3 PUFA groups. After stabilization of BP in the 3 groups, the rats received a short administration of increasing dose of perindopril. The lower dose (0.5 mg/kg) moderately decreased BP only in the control group. With higher doses (1, 5 and 10 mg/kg) BP was normalized in the 3 groups, with a higher amplitude of the BP lowering effect in the control group. A moderate n-3 PUFA intake can contribute to prevent the development of peripheral hypertension in rats by a mechanism that may involve angiotensin converting enzyme.
n-3 Polyunsaturated Fatty Acids Reduce Neonatal Hypoxic/Ischemic Brain Injury by Promoting Phosphatidylserine Formation and Akt Signaling.

PubMed

Zhang, Wenting; Liu, Jia; Hu, Xiaoming; Li, Peiying; Leak, Rehana K; Gao, Yanqin; Chen, Jun

2015-10-01

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate neonatal hypoxic/ischemic (H/I) brain damage, but the underlying mechanisms are not fully understood. This study tested the hypothesis that n-3 PUFAs enhance Akt-dependent prosurvival signaling by promoting the biosynthesis of phosphatidylserine in neuronal cell membranes. Dietary n-3 PUFA supplementation was initiated on the second day of pregnancy in dams. H/I was induced in 7-day-old rat pups by ipsilateral common carotid artery occlusion followed by hypoxia (8% oxygen for 2.5 hours). Neurological outcomes, brain tissue loss, cell death, and the activation of signaling events were assessed after H/I. The effects of n-3 PUFAs (docosahexaenoic acid and eicosapentaenoic acid) on oxygen-glucose deprivation-induced cell death and the underlying mechanism of protection were also examined in primary cortical neuron cultures. n-3 PUFAs reduced brain tissue loss at 7 days after H/I and improved neurological outcomes, whereas inhibition of PI3K/Akt signaling by LY294002 partially abrogated this neuroprotective effect. Docosahexaenoic acid/eicosapentaenoic acid also prevented ischemic neuronal death through the Akt prosurvival pathway in vitro. Furthermore, docosahexaenoic acid/eicosapentaenoic acid increased the production of phosphatidylserine, the major membrane-bound phospholipids, after ischemia both in vitro and in vivo. A reduction in membrane phosphatidylserine by shRNA-mediated knockdown of phosphatidylserine synthetase-1 attenuated Akt activation and neuronal survival after docosahexaenoic acid/eicosapentaenoic acid treatment in the oxygen-glucose deprivation model. n-3 PUFAs robustly protect against H/I-induced brain damage in neonates by activating Akt prosurvival pathway in compromised neurons. In addition, n-3 PUFAs promote the formation of membrane phosphatidylserine, thereby promoting Akt activity and improving cellular survival. © 2015 American Heart Association, Inc.

Impulsivity-based thrifty eating phenotype and the protective role of n-3 PUFAs intake in adolescents.

PubMed

Reis, R S; Dalle Molle, R; Machado, T D; Mucellini, A B; Rodrigues, D M; Bortoluzzi, A; Bigonha, S M; Toazza, R; Salum, G A; Minuzzi, L; Buchweitz, A; Franco, A R; Pelúzio, M C G; Manfro, G G; Silveira, P P

2016-03-15

The goal of the present study was to investigate whether intrauterine growth restriction (IUGR) affects brain responses to palatable foods and whether docosahexaenoic acid (DHA, an omega-3 fatty acid that is a primary structural component of the human brain) serum levels moderate the association between IUGR and brain and behavioral responses to palatable foods. Brain responses to palatable foods were investigated using a functional magnetic resonance imaging task in which participants were shown palatable foods, neutral foods and non-food items. Serum DHA was quantified in blood samples, and birth weight ratio (BWR) was used as a proxy for IUGR. The Dutch Eating Behavior Questionnaire (DEBQ) was used to evaluate eating behaviors. In the contrast palatable food > neutral items, we found an activation in the right superior frontal gyrus with BWR as the most important predictor; the lower the BWR (indicative of IUGR), the greater the activation of this region involved in impulse control/decision making facing the viewing of palatable food pictures versus neutral items. At the behavioral level, a general linear model predicting external eating using the DEBQ showed a significant interaction between DHA and IUGR status; in IUGR individuals, the higher the serum DHA, the lower is external eating. In conclusion, we suggest that IUGR moderates brain responses when facing stimuli related to palatable foods, activating an area related to impulse control. Moreover, higher intake of n-3 PUFAs can protect IUGR individuals from developing inappropriate eating behaviors, the putative mechanism of protection would involve decreasing intake in response to external food cues in adolescents/young adults.
Impulsivity-based thrifty eating phenotype and the protective role of n-3 PUFAs intake in adolescents

PubMed Central

Reis, R S; Dalle Molle, R; Machado, T D; Mucellini, A B; Rodrigues, D M; Bortoluzzi, A; Bigonha, S M; Toazza, R; Salum, G A; Minuzzi, L; Buchweitz, A; Franco, A R; Pelúzio, M C G; Manfro, G G; Silveira, P P

2016-01-01

The goal of the present study was to investigate whether intrauterine growth restriction (IUGR) affects brain responses to palatable foods and whether docosahexaenoic acid (DHA, an omega-3 fatty acid that is a primary structural component of the human brain) serum levels moderate the association between IUGR and brain and behavioral responses to palatable foods. Brain responses to palatable foods were investigated using a functional magnetic resonance imaging task in which participants were shown palatable foods, neutral foods and non-food items. Serum DHA was quantified in blood samples, and birth weight ratio (BWR) was used as a proxy for IUGR. The Dutch Eating Behavior Questionnaire (DEBQ) was used to evaluate eating behaviors. In the contrast palatable food > neutral items, we found an activation in the right superior frontal gyrus with BWR as the most important predictor; the lower the BWR (indicative of IUGR), the greater the activation of this region involved in impulse control/decision making facing the viewing of palatable food pictures versus neutral items. At the behavioral level, a general linear model predicting external eating using the DEBQ showed a significant interaction between DHA and IUGR status; in IUGR individuals, the higher the serum DHA, the lower is external eating. In conclusion, we suggest that IUGR moderates brain responses when facing stimuli related to palatable foods, activating an area related to impulse control. Moreover, higher intake of n-3 PUFAs can protect IUGR individuals from developing inappropriate eating behaviors, the putative mechanism of protection would involve decreasing intake in response to external food cues in adolescents/young adults. PMID:26978737
The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

PubMed

Nishi, Daisuke; Su, Kuan-Pin; Usuda, Kentaro; Chiang, Yi-Ju Jill; Guu, Tai-Wei; Hamazaki, Kei; Nakaya, Naoki; Sone, Toshimasa; Sano, Yo; Tachibana, Yoshiyuki; Ito, Hiroe; Isaka, Keiich; Hashimoto, Kenji; Hamazaki, Tomohito; Matsuoka, Yutaka J

2016-09-15

Maternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here. The Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks' follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018. The trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations. Clinicaltrials.gov: NCT
Apolipoprotein C-III, n-3 polyunsaturated fatty acids, and "insulin-resistant" T-455C APOC3 gene polymorphism in heart disease patients: example of gene-diet interaction.

PubMed

Olivieri, Oliviero; Martinelli, Nicola; Sandri, Marco; Bassi, Antonella; Guarini, Patrizia; Trabetti, Elisabetta; Pizzolo, Francesca; Girelli, Domenico; Friso, Simonetta; Pignatti, Pier Franco; Corrocher, Roberto

2005-02-01

Apolipoprotein C-III (apo C-III) is a marker of cardiovascular disease risk associated with triglyceride (TG)-rich lipoproteins. The T-455C polymorphism in the insulin-responsive element of the APOC3 gene influences TG and apo C-III concentrations. Long-chain n-3 polyunsaturated fatty acids (PUFAs) contained in fish have well-known apo C-III-lowering properties. We investigated the possibility of an interactive effect between the APOC3 gene variant and erythrocyte n-3 PUFAs, suitable markers of dietary intake of fatty acids, on apo C-III concentrations in a population of 848 heart disease patients who had coronary angiography. In the population as a whole, apo C-III concentrations were significantly inversely correlated with total erythrocyte PUFAs, but the correlation was not significant when only -455CC homozygous individuals were taken into account. In the total population and in subgroups with the -455TT and -455CT genotypes, the relative proportions of individuals presenting with increased apo C-III (i.e., above the 75th percentile value calculated on the entire population after exclusion of individuals taking lipids-lowering medications) decreased progressively as the n-3 PUFA and docosahexaenoic acid concentrations increased. The opposite situation was observed in the homozygous -455CC subgroup, in whom increasing erythrocyte n-3 PUFA and docosahexaenoic acid concentrations were associated with higher proportions of individuals with high apo C-III. A formal interactive effect between genotype and n-3 PUFAs was confirmed even after adjustment for possible confounding variables [age, sex, body mass index, smoking, coronary artery disease (CAD)/CAD-free status, or use of lipid-lowering medications] by logistic models. Patients homozygous for the -455C APOC3 variant are poorly responsive to the apo C-III-lowering effects of n-3 PUFAs.
Dietary n-3 polyunsaturated fatty acids and the paradox of their health benefits and potential harmful effects.

PubMed

Serini, Simona; Fasano, Elena; Piccioni, Elisabetta; Cittadini, Achille R M; Calviello, Gabriella

2011-12-19

There is some evidence to support the toxicity of polyunsaturated fatty acids (PUFAs) and their oxidative products, suggesting their involvement in the pathogenesis of different chronic diseases, including cancer. It has been shown that products of PUFA oxidation may exert a carcinogenic action by forming mutagenic adducts with DNA. However, a large amount of evidence accumulated over several decades has indicated the beneficial effects of administration of n-3 PUFAs in the prevention and therapy of a series of diseases. In particular, there is much evidence that n-3 PUFAs exert anti-inflammatory and antineoplastic effects, whereas n-6 PUFAs promote inflammation and carcinogenesis. In our tissues, both of the two classes of PUFAs can be converted into bioactive products, incorporated into membrane phospholipids or bound to membrane receptors, where they may alter, often in opposite ways, transduction pathways and affect important biological processes, such as cell death and survival, inflammation, and neo-angiogenesis. In the present review, we intend to shed light on the paradox of the coexisting healthy and toxic effects of n-3 PUFAs, focusing on their possible pro-oxidant cytotoxic and carcinogenic effect, in order to understand if their increased intake, recommended by a number of health agencies worldwide and promoted by nutraceutical producers, may or may not represent a hazard to human health. © 2011 American Chemical Society
Systematic Review on N-3 and N-6 Polyunsaturated Fatty Acid Intake in European Countries in Light of the Current Recommendations - Focus on Specific Population Groups.

PubMed

Sioen, Isabelle; van Lieshout, Lilou; Eilander, Ans; Fleith, Mathilde; Lohner, Szimonetta; Szommer, Alíz; Petisca, Catarina; Eussen, Simone; Forsyth, Stewart; Calder, Philip C; Campoy, Cristina; Mensink, Ronald P

2017-01-01

Earlier reviews indicated that in many countries adults, children and adolescents consume on an average less polyunsaturated fatty acids (PUFAs) than recommended by the Food and Agriculture Organisation/World Health Organisation. The intake of total and individual n-3 and n-6 PUFAs in European infants, children, adolescents, elderly and pregnant/lactating women was evaluated systematically. The evaluations were done against recommendations of the European Food Safety Authority. Key Messages: Fifty-three studies from 17 different European countries reported an intake of total n-3 and n-6 PUFAs and/or individual n-3 or n-6 PUFAs in at least one of the specific population groups: 10 in pregnant women, 4 in lactating women, 3 in infants 6-12 months, 6 in children 1-3 years, 11 in children 4-9 years, 8 in adolescents 10-18 years and 11 in elderly >65 years. Mean linoleic acid intake was within the recommendation (4 energy percentage [E%]) in 52% of the countries, with inadequate intakes more likely in lactating women, adolescents and elderly. Mean α-linolenic acid intake was within the recommendation (0.5 E%) in 77% of the countries. In 26% of the countries, mean eicosapentaenoic acid and/or docosahexaenoic acid intake was as recommended. These results indicate that intake of n-3 and n-6 PUFAs may be suboptimal in specific population groups in Europe. © 2017 S. Karger AG, Basel.
Dietary (n-6 : n-3) Fatty Acids Alter Plasma and Tissue Fatty Acid Composition in Pregnant Sprague Dawley Rats

PubMed Central

Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

2012-01-01

The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat. PMID:22489205
Omega-3 PUFA concentration by a novel PVDF nano-composite membrane filled with nano-porous silica particles.

PubMed

Ghasemian, Samaneh; Sahari, Mohammad Ali; Barzegar, Mohsen; Ahmadi Gavlighi, Hasan

2017-09-01

In this study, polyvinylidene fluoride (PVDF) and nano-porous silica particle were used to fabricate an asymmetric nano-composite membrane. Silica particles enhanced the thermal stability of PVDF/SiO 2 membranes; increasing the decomposition temperature from 371°C to 408°C. Cross sectional morphology showed that silica particles were dispersed in polymer matrix uniformly. However, particle agglomeration was found at higher loading of silica (i.e., 20 by weight%). The separation performance of nano-composite membranes was also evaluated using the omega-3 polyunsaturated fatty acids (PUFA) concentration at a temperature and pressure of 30°C and 4bar, respectively. Silica particle increased the omega-3PUFA concentration from 34.8 by weight% in neat PVDF to 53.9 by weight% in PVDF with 15 by weight% of silica. Moreover, PVDF/SiO 2 nano-composite membranes exhibited enhanced anti-fouling property compared to neat PVDF membrane. Fouling mechanism analysis revealed that complete pore blocking was the predominant mechanism occurring in oil filtration. The concentration of omega-3 polyunsaturated fatty acids (PUFA) is important in the oil industries. While the current methods demand high energy consumptions in concentrating the omega-3, membrane separation technology offers noticeable advantages in producing pure omega-3 PUFA. Moreover, concentrating omega-3 via membrane separation produces products in the triacylglycerol form which possess better oxidative stability. In this work, the detailed mechanisms of fouling which limits the performance of membrane separation were investigated. Incorporating silica particles to polymeric membrane resulted in the formation of mixed matrix membrane with improved anti-fouling behaviour compared to the neat polymeric membrane. Hence, the industrial potential of membrane processing to concentrate omega-3 fatty acids is enhanced. Copyright © 2017. Published by Elsevier Ltd.
Role of n-3 Polyunsaturated Fatty Acids in Ameliorating the Obesity-Induced Metabolic Syndrome in Animal Models and Humans

PubMed Central

Huang, Chao-Wei; Chien, Yi-Shan; Chen, Yu-Jen; Ajuwon, Kolapo M.; Mersmann, Harry M.; Ding, Shih-Torng

2016-01-01

The incidence of obesity and its comorbidities, such as insulin resistance and type II diabetes, are increasing dramatically, perhaps caused by the change in the fatty acid composition of common human diets. Adipose tissue plays a role as the major energy reservoir in the body. An excess of adipose mass accumulation caused by chronic positive energy balance results in obesity. The n-3 polyunsaturated fatty acids (n-3 PUFA), DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) exert numerous beneficial effects to maintain physiological homeostasis. In the current review, the physiology of n-3 PUFA effects in the body is delineated from studies conducted in both human and animal experiments. Although mechanistic studies in human are limited, numerous studies conducted in animals and models in vitro provide potential molecular mechanisms of the effects of these fatty acids. Three aspects of n-3 PUFA in adipocyte regulation are discussed: (1) lipid metabolism, including adipocyte differentiation, lipolysis and lipogenesis; (2) energy expenditure, such as mitochondrial and peroxisomal fatty acid β-oxidation; and (3) inflammation, including adipokines and specialized pro-resolving lipid mediators. Additionally, the mechanisms by which n-3 PUFA regulate gene expression are highlighted. The beneficial effects of n-3 PUFA may help to reduce the incidence of obesity and its comorbidities. PMID:27735847
Systematic Review on N-3 and N-6 Polyunsaturated Fatty Acid Intake in European Countries in Light of the Current Recommendations – Focus on Specific Population Groups

PubMed Central

Sioen, Isabelle; van Lieshout, Lilou; Eilander, Ans; Fleith, Mathilde; Lohner, Szimonetta; Szommer, Alíz; Petisca, Catarina; Eussen, Simone; Forsyth, Stewart; Calder, Philip C.; Campoy, Cristina; Mensink, Ronald P.

2017-01-01

Background Earlier reviews indicated that in many countries adults, children and adolescents consume on an average less polyunsaturated fatty acids (PUFAs) than recommended by the Food and Agriculture Organisation/World Health Organisation. Summary The intake of total and individual n-3 and n-6 PUFAs in European infants, children, adolescents, elderly and pregnant/lactating women was evaluated systematically. Results The evaluations were done against recommendations of the European Food Safety Authority. Key Messages Fifty-three studies from 17 different European countries reported an intake of total n-3 and n-6 PUFAs and/or individual n-3 or n-6 PUFAs in at least one of the specific population groups: 10 in pregnant women, 4 in lactating women, 3 in infants 6–12 months, 6 in children 1–3 years, 11 in children 4–9 years, 8 in adolescents 10–18 years and 11 in elderly >65 years. Mean linoleic acid intake was within the recommendation (4 energy percentage [E%]) in 52% of the countries, with inadequate intakes more likely in lactating women, adolescents and elderly. Mean α-linolenic acid intake was within the recommendation (0.5 E%) in 77% of the countries. In 26% of the countries, mean eicosapentaenoic acid and/or docosahexaenoic acid intake was as recommended. These results indicate that intake of n-3 and n-6 PUFAs may be suboptimal in specific population groups in Europe. PMID:28190013
Dietary flavonoids increase plasma very long-chain (n-3) fatty acids in rats.

PubMed

Toufektsian, Marie-Claire; Salen, Patricia; Laporte, François; Tonelli, Chiara; de Lorgeril, Michel

2011-01-01

Flavonoids probably contribute to the health benefits associated with the consumption of fruit and vegetables. However, the mechanisms by which they exert their effects are not fully elucidated. PUFA of the (n-3) series also have health benefits. Epidemiological and clinical studies have suggested that wine flavonoids may interact with the metabolism of (n-3) PUFA and increase their blood and cell levels. The present studies in rats were designed to assess whether flavonoids actually increase plasma levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main very long-chain (n-3) PUFA. Rats were fed a corn-derived anthocyanin (ACN)-rich (ACN-rich) or ACN-free diet with constant intakes of plant and marine (n-3) PUFA for 8 wk (Expt. 1). Plasma fatty acids were measured by GC. The ACN-rich diet contained ~0.24 ± 0.01 mg of ACN/g pellets. There were no significant differences between groups in the main saturated, monounsaturated, and (n-6) fatty acids. In contrast, plasma EPA and DHA were greater in the ACN-rich diet group than in the ACN-free diet group (P < 0.05). We obtained similar results in 2 subsequent experiments in which rats were administered palm oil (80 μL/d) and consumed the ACN-rich or ACN-free diet (Expt. 2) or were supplemented with fish oil (60 mg/d, providing 35 mg DHA and 12 mg EPA) and consumed the ACN-rich or ACN-free diet (Expt. 3). In both experiments, plasma EPA and DHA were significantly greater in the ACN-rich diet group. These studies demonstrate that the consumption of flavonoids increases plasma very long-chain (n-3) PUFA levels. These data confirm previous clinical and epidemiological studies and provide new insights into the health benefits of flavonoids.
PUFA Status and Methylmercury Exposure Are Not Associated with Leukocyte Telomere Length in Mothers or Their Children in the Seychelles Child Development Study.

PubMed

Yeates, Alison J; Thurston, Sally W; Li, Huiqi; Mulhern, Maria S; McSorley, Emeir M; Watson, Gene E; Shamlaye, Conrad F; Strain, J J; Myers, Gary J; Davidson, Philip W; van Wijngaarden, Edwin; Broberg, Karin

2017-11-01

Background: Leukocyte telomere length (TL) is associated with age-related diseases and early mortality, but there is a lack of data on the determinants of TL in early life. Evidence suggests that dietary intake of marine n-3 (ω-3) polyunsaturated fatty acids (PUFAs) is protective of telomere attrition, yet the effect of methylmercury exposure, also found in fish, on TL is unknown. Objective: The aim of this study was to investigate the associations between prenatal PUFA status, methylmercury exposure, and TL in mothers and children in the SCDS (Seychelles Child Development Study), for whom fish consumption is high. Methods: Blood samples collected from 229 mothers (at 28 wk gestation and delivery) and children (at 5 y of age) in the SCDS first nutrition cohort were analyzed for PUFA concentrations. Prenatal mercury was measured in maternal hair collected at delivery. Postnatal mercury was also measured in children's hair samples with the use of a cumulative metric derived from values obtained at 3-5 y of age. Relative TL was measured in blood obtained from mothers at delivery, in cord blood, and in children at 5 y of age by quantitative polymerase chain reaction. Linear regression models were used to investigate the associations between PUFA status, methylmercury exposure, and TL. Results: Neither prenatal PUFA status or methylmercury exposure was associated with TL of the mother or child or with TL attrition rate. However, a higher prenatal n-6:n-3 PUFA ratio was significantly associated with longer TLs in the mothers (β = 0.001, P = 0.048). Child PUFA status and methylmercury exposure were not associated with child TL. However, higher family Hollingshead socioeconomic status (SES) scores at 9 mo of age were significantly associated with longer TLs in cord blood (β = 0.005, P = 0.03). Conclusions: We found no evidence that PUFA status or methylmercury exposure are determinants of TL in either the mother or child. However, our results support the hypothesis that
In male rats with concurrent iron and (n-3) fatty acid deficiency, provision of either iron or (n-3) fatty acids alone alters monoamine metabolism and exacerbates the cognitive deficits associated with combined deficiency.

PubMed

Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

2012-08-01

Concurrent deficiencies of iron (Fe) (ID) and (n-3) fatty acids [(n-3)FAD)] in rats can alter brain monoamine pathways and impair learning and memory. We examined whether repletion with Fe and DHA/EPA, alone and in combination, corrects the deficits in brain monoamine activity (by measuring monoamines and related gene expression) and spatial working and reference memory [by Morris water maze (MWM) testing] associated with deficiency. Using a 2 × 2 design, male rats with concurrent ID and (n-3)FAD [ID+(n-3)FAD] were fed an Fe+DHA/EPA, Fe+(n-3)FAD, ID+DHA/EPA, or ID+(n-3)FAD diet for 5 wk [postnatal d 56-91]. Biochemical measures and MWM performance after repletion were compared to age-matched control rats. The provision of Fe in combination with DHA/EPA synergistically increased Fe concentrations in the olfactory bulb (OB) (Fe x DHA/EPA interaction). Similarly, provision of DHA/EPA in combination with Fe resulted in higher brain DHA concentrations than provision of DHA alone in the frontal cortex (FC) and OB (P < 0.05). Dopamine (DA) receptor D1 was upregulated in the hippocampus of Fe+DHA/EPA rats (fold-change = 1.25; P < 0.05) and there were significant Fe x DHA/EPA interactions on serotonin (5-HT) in the OB and on the DA metabolite dihydroxyphenylacetic acid in the FC and striatum. Working memory performance was impaired in ID+DHA/EPA rats compared with controls (P < 0.05). In the reference memory task, Fe+DHA/EPA improved learning behavior, but Fe or DHA/EPA alone did not. These findings suggest that feeding either Fe or DHA/EPA alone to adult rats with both ID and (n-3)FAD affects the DA and 5-HT pathways differently than combined repletion and exacerbates the cognitive deficits associated with combined deficiency.
n-3 fatty acid enrichment of edible tissue of poultry: a review.

PubMed

Rymer, C; Givens, D I

2005-02-01

There is clear evidence of the nutritional benefits of consuming long-chain n-3 PUFA, which are found predominantly in oily fish. However, oily fish consumption, particularly in the United Kingdom, is declining, as is the consumption of all meats with the exception of poultry, which has increased in consumption by 73% in the last 30 yr. This pattern, if less marked, is reflected throughout Europe, and therefore one means of increasing long-chain n-3 PUFA consumption would be to increase the long-chain n-3 PUFA content in the edible tissues of poultry. This review considers the feasibility of doing this, concentrating particularly on chickens and turkeys. It begins by summarizing the benefits to human health of consuming greater quantities of n-3 FA and the sources of n-3 PUFA in the human diet. The literature on altering the FA composition of poultry meat is then reviewed, and the factors affecting the incorporation of n-3 PUFA into edible tissues of poultry are investigated. The concentration of alpha-linolenic acid (ALA) in the edible tissues of poultry is readily increased by increasing the concentration of ALA in the birds' diet (particularly meat with skin, and dark meat to a greater extent than white meat). The concentration of EPA in both white and dark meat is also increased when the birds' diet is supplemented with EPA, although supplementing the diet with the precursor (ALA) does not result in a noticeable increase in EPA content in the edible tissues. Although supplementing the birds' diets with relatively high concentrations of DHA does result in an increased concentration of DHA in the tissues, the relationship between dietary and tissue concentrations of DHA is much weaker than that observed with ALA and EPA. The impact that altering the FA composition of edible poultry tissue may have on the organoleptic and storage qualities of poultry products is also considered.
Effect of PUFAs Oral Administration on the Amount of Apoptotic Caspases Enzymes in Gastric Cancer Patients Undergoing Chemotherapy.

PubMed

Dolatkhah, Homayun; Movahedian, Ahmad; Somi, Mohammad-Hossein; Aghaei, Mahmud; Samadi, Naser; Mirza-Aghazade, Ahmad; Esfahani, Ali

2017-01-01

in individuals' mitochondria-dependent apoptosis. As PUFAs enhances caspase-3 and 9 genes expression levels, which is an important induce the mitochondrial dependent apoptosis process. The study was registered in Iran clinical trials registry center under No. IRCT2014031016922N1.
Dietary PUFA and flavonoids as deterrents for environmental pollutants.

PubMed

Watkins, Bruce A; Hannon, Kevin; Ferruzzi, Mario; Li, Yong

2007-03-01

Various nutrients and plant-derived phytochemicals are associated with a reduced risk of many diet-related chronic diseases including cardiovascular disease, cancer, diabetes, arthritis and osteoporosis. A common theme that links many chronic diseases is uncontrolled inflammation. The long-chain (LC) omega-3 polyunsaturated fatty acids (PUFA) and flavonoids are known to possess anti-inflammatory actions in cell cultures, animal models and humans. Minimizing the condition of persistent inflammation has been a primary aim for drug development, but understanding how food components attenuate this process is at the nexus for improving the human condition. The prevalence of environmental toxins such as heavy metals and organics that contribute to diminished levels of antioxidants likely aggravates inflammatory states when intakes of omega-3 PUFA and flavonoids are marginal. Scientists at Purdue University have formed a collaboration to better understand the metabolism and physiology of flavonoids. This new effort is focused on determining how candidate flavonoids and their metabolites affect gene targets of inflammation in cell culture and animal models. The challenge of this research is to understand how LC omega-3 PUFA and flavonoids affect the biology of inflammation. The goal is to determine how nutrients and phytochemicals attenuate chronic inflammation associated with a number of diet-related diseases that occur throughout the life cycle. The experimental approach involves molecular, biochemical and physiological endpoints of aging, cancer, obesity and musculoskeletal diseases. Examples include investigations on the combined effects of PUFA and cyanidins on inflammatory markers in cultures of human cancer cells. The actions of catechins and PUFA on muscle loss and osteopenia are being studied in a rodent model of disuse atrophy to explain how muscle and bone communicate to prevent tissue loss associated with injury, disease and aging. The purpose of this review is
Effect of cooking method on the fatty acid content of reduced-fat and PUFA-enriched pork patties formulated with a konjac-based oil bulking system.

PubMed

Salcedo-Sandoval, Lorena; Cofrades, Susana; Ruiz-Capillas, Claudia; Jiménez-Colmenero, Francisco

2014-12-01

The effect of cooking methods (electric grilling and pan-frying in olive oil) on the composition of reduced-fat and reduced-fat/PUFA enriched pork patties was studied. Fat reduction was performed by replacing pork backfat (38% and 100%) with konjac gel and PUFA-enrichment by replacing pork backfat (49%) with a konjac-based oil bulking system stabilizing a healthier oil combination (olive, linseed and fish oils). Cooking losses (13%-27%) were affected (p<0.05) by formulation and cooking procedure. Compared with raw products, cooked samples had higher (p<0.05) concentrations of MUFAs and PUFAs (both n-3 and n-6); the difference was greater (p<0.05) in the pan-fried patties. Fatty acid retention was generally better in pan-fried than in grilled samples. When cooked, the PUFA levels in the medium-fat/improved sample containing the oil bulking system ranged between 1.4 and 1.6g/100g (0.47-0.51 from n-3 PUFAs), with EPA+DHA concentrations of around 75mg/100g. Konjac materials were successfully used to produce pork patties with a better lipid composition. Copyright © 2014. Published by Elsevier Ltd.
The effect of feeding modified soyabean oil enriched with C18 : 4 n-3 to broilers on the deposition of n-3 fatty acids in chicken meat.

PubMed

Rymer, C; Hartnell, G F; Givens, D I

2011-03-01

Supplementing broiler diets with conventional vegetable oils has little effect on the long-chain n-3 PUFA (LC n-3 PUFA) content of the meat. The present study investigated the effect on fatty acid composition and sensory characteristics of chicken meat when broilers were fed oil extracted from soyabeans (SDASOY) that had been genetically engineered to produce C18 : 4n-3 (stearidonic acid (SDA), 240 mg/g oil). Three diets were fed to 120 birds (eight replicate pens of five birds) from 15 d to slaughter (41-50 d). Diets were identical apart from the oil added to them (45 and 50 g/kg as fed in the grower and finisher phases, respectively), which was either SDASOY, near-isogenic soya (CON) or fish oil (FISH). The LC n-3 PUFA content of the meat increased in the order CON, SDASOY and FISH. In breast meat with skin, the SDA concentration was 522, 13 and 37 (sem 14·4) mg/100 g meat for SDASOY, CON and FISH, respectively. Equivalent values for C20 : 5n-3 (EPA) were 53, 13 and 140 (sem 8·4); for C22 : 5n-3 (docosapentaenoic acid (DPA)) 65, 15 and 101 (sem 3·5); for C22 : 6n-3 (DHA) 19, 9 and 181 (sem 4·4). Leg meat (with skin) values for SDA were 861, 23 and 68 (sem 30·1); for EPA 87, 9 and 258 (sem 7·5); for DPA 95, 20 and 165 (sem 5·0); for DHA 29, 10 and 278 (sem 8·4). Aroma, taste and aftertaste of freshly cooked breast meat were not affected. Fishy aromas, tastes and aftertastes were associated with LC n-3 PUFA content of the meat, being most noticeable in the FISH leg meat (both freshly cooked and reheated) and in the reheated SDASOY leg meat.
Isolation and Characterization of the Diatom Phaeodactylum Δ5-Elongase Gene for Transgenic LC-PUFA Production in Pichia pastoris

PubMed Central

Jiang, Mulan; Guo, Bing; Wan, Xia; Gong, Yangmin; Zhang, Yinbo; Hu, Chuanjiong

2014-01-01

The diatom Phaeodactylum tricornutum can accumulate eicosapentaenoic acid (EPA) up to 30% of the total fatty acids. This species has been targeted for isolating gene encoding desaturases and elongases for long-chain polyunsaturated fatty acid (LC-PUFA) metabolic engineering. Here we first report the cloning and characterization of Δ5-elongase gene in P. tricornutum. A full-length cDNA sequence, designated PhtELO5, was shown to contain a 1110 bp open reading frame encoding a 369 amino acid polypeptide. The putative protein contains seven transmembrane regions and two elongase characteristic motifs of FLHXYHH and MYSYY, the latter being typical for microalgal Δ5-elongases. Phylogenetic analysis indicated that PhtELO5 belongs to the ELO5 group, tightly clustered with the counterpart of Thalassiosira pseudonana. Heterologous expression of PhtELO5 in Pichia pastoris confirmed that it encodes a specific Δ5-elongase capable of elongating arachidonic acid and eicosapentaenoic acid. Co-expression of PhtELO5 and IsFAD4 (a ∆4-desaturase from Isochrysis sphaerica) demonstrated that the high-efficiency biosynthetic pathway of docosahexaenoic acid was assembled in the transgenic yeast. Substrate competition revealed that PhtELO5 exhibited higher activity towards n-3 PUFA than n-6 PUFA. It is hypothesized that Phaeodactylum ELO5 may preferentially participate in biosynthesis of transgenic LC-PUFA via a n-3 pathway in the yeast host. PMID:24608969
Maternal Diet Supplementation with n-6/n-3 Essential Fatty Acids in a 1.2 : 1.0 Ratio Attenuates Metabolic Dysfunction in MSG-Induced Obese Mice

PubMed Central

Martin, Josiane Morais; Miranda, Rosiane Aparecida; Palma-Rigo, Kesia; Alves, Vander Silva; Fabricio, Gabriel Sergio; Pavanello, Audrei; Franco, Claudinéia Conationi da Silva; Ribeiro, Tatiane Aparecida; Visentainer, Jesuí Vergílio; Banafé, Elton Guntendeorfer; Martin, Clayton Antunes; Mathias, Paulo Cezar de Freitas

2016-01-01

Essential polyunsaturated fatty acids (PUFAs) prevent cardiometabolic diseases. We aimed to study whether a diet supplemented with a mixture of n-6/n-3 PUFAs, during perinatal life, attenuates outcomes of long-term metabolic dysfunction in prediabetic and obese mice. Seventy-day-old virgin female mice were mated. From the conception day, dams were fed a diet supplemented with sunflower oil and flaxseed powder (containing an n-6/n-3 PUFAs ratio of 1.2 : 1.0) throughout pregnancy and lactation, while control dams received a commercial diet. Newborn mice were treated with monosodium L-glutamate (MSG, 4 mg g−1 body weight per day) for the first 5 days of age. A batch of weaned pups was sacrificed to quantify the brain and pancreas total lipids; another batch were fed a commercial diet until 90 days of age, where glucose homeostasis and glucose-induced insulin secretion (GIIS) as well as retroperitoneal fat and Lee index were assessed. MSG-treated mice developed obesity, glucose intolerance, insulin resistance, pancreatic islet dysfunction, and higher fat stores. Maternal flaxseed diet-supplementation decreased n-6/n-3 PUFAs ratio in the brain and pancreas and blocked glucose intolerance, insulin resistance, GIIS impairment, and obesity development. The n-6/n-3 essential PUFAs in a ratio of 1.2 : 1.0 supplemented in maternal diet during pregnancy and lactation prevent metabolic dysfunction in MSG-obesity model. PMID:28050167

N-3 fatty acids reduced trans fatty acids retention and increased docosahexaenoic acid levels in the brain.

PubMed

Lavandera, Jimena Verónica; Saín, Juliana; Fariña, Ana Clara; Bernal, Claudio Adrián; González, Marcela Aída

2017-09-01

The levels of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are critical for the normal structure and function of the brain. Trans fatty acids (TFA) and the source of the dietary fatty acids (FA) interfere with long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis. The aim of this study was to investigate the effect of TFA supplementation in diets containing different proportions of n-9, n-6, and n-3 FA on the brain FA profile, including the retention of TFA, LC-PUFA levels, and n-6/n-3 PUFA ratios. These parameters were also investigated in the liver, considering that LC-PUFA are mainly bioconverted from their dietary precursors in this tissue and transported by serum to the brain. Also, stearoyl-CoA desaturase-1 (SCD1) and sterol regulatory element-binding protein-1c (SREBP-1c) gene expressions were evaluated. Male CF1 mice were fed (16 weeks) diets containing different oils (olive, corn, and rapeseed) with distinct proportions of n-9, n-6, and n-3 FA (55.2/17.2/0.7, 32.0/51.3/0.9, and 61.1/18.4/8.6), respectively, substituted or not with 0.75% of TFA. FA composition of the brain, liver, and serum was assessed by gas chromatography. TFA were incorporated into, and therefore retained in the brain, liver, and serum. However, the magnitude of retention was dependent on the tissue and type of isomer. In the brain, total TFA retention was lower than 1% in all diets. Dietary n-3 PUFA decreased TFA retention and increased DHA accretion in the brain. The results underscore the importance of the type of dietary FA on the retention of TFA in the brain and also on the changes of the FA profile.
Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid.

PubMed

Markworth, James F; Kaur, Gunveen; Miller, Eliza G; Larsen, Amy E; Sinclair, Andrew J; Maddipati, Krishna Rao; Cameron-Smith, David

2016-11-01

In contrast to the well-characterized effects of specialized proresolving lipid mediators (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little is known about the metabolic fate of the intermediary long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) docosapentaenoic acid (DPA). In this double blind crossover study, shifts in circulating levels of n-3 and n-6 PUFA-derived bioactive lipid mediators were quantified by an unbiased liquid chromatography-tandem mass spectrometry lipidomic approach. Plasma was obtained from human subjects before and after 7 d of supplementation with pure n-3 DPA, n-3 EPA or placebo (olive oil). DPA supplementation increased the SPM resolvin D5 n -3DPA (RvD5 n -3DPA ) and maresin (MaR)-1, the DHA vicinal diol 19,20-dihydroxy-DPA and n-6 PUFA derived 15-keto-PG E 2 (15-keto-PGE 2 ). EPA supplementation had no effect on any plasma DPA or DHA derived mediators, but markedly elevated monohydroxy-eicosapentaenoic acids (HEPEs), including the e-series resolvin (RvE) precursor 18-HEPE; effects not observed with DPA supplementation. These data show that dietary n-3 DPA and EPA have highly divergent effects on human lipid mediator profile, with no overlap in PUFA metabolites formed. The recently uncovered biologic activity of n-3 DPA docosanoids and their marked modulation by dietary DPA intake reveals a unique and specific role of n-3 DPA in human physiology.-Markworth, J. F., Kaur, G., Miller, E. G., Larsen, A. E., Sinclair, A. J., Maddipati, K. R., Cameron-Smith, D. Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid. © FASEB.
Enhanced increase of omega-3 index in healthy individuals with response to 4-week n-3 fatty acid supplementation from krill oil versus fish oil.

PubMed

Ramprasath, Vanu R; Eyal, Inbal; Zchut, Sigalit; Jones, Peter J H

2013-12-05

Due to structural differences, bioavailability of krill oil, a phospholipid based oil, could be higher than fish oil, a triglyceride-based oil, conferring properties that render it more effective than fish oil in increasing omega-3 index and thereby, reducing cardiovascular disease (CVD) risk. The objective was to assess the effects of krill oil compared with fish oil or a placebo control on plasma and red blood cell (RBC) fatty acid profile in healthy volunteers. Twenty four healthy volunteers were recruited for a double blinded, randomized, placebo-controlled, crossover trial. The study consisted of three treatment phases including krill or fish oil each providing 600 mg of n-3 polyunsaturated fatty acids (PUFA) or placebo control, corn oil in capsule form. Each treatment lasted 4 wk and was separated by 8 wk washout phases. Krill oil consumption increased plasma (p = 0.0043) and RBC (p = 0.0011) n-3 PUFA concentrations, including EPA and DHA, and reduced n-6:n-3 PUFA ratios (plasma: p = 0.0043, RBC: p = 0.0143) compared with fish oil consumption. Sum of EPA and DHA concentrations in RBC, the omega-3 index, was increased following krill oil supplementation compared with fish oil (p = 0.0143) and control (p < 0.0001). Serum triglycerides and HDL cholesterol concentrations did not change with any of the treatments. However, total and LDL cholesterol concentrations were increased following krill (TC: p = 0.0067, LDL: p = 0.0143) and fish oil supplementation (TC: p = 0.0028, LDL: p = 0.0143) compared with control. Consumption of krill oil was well tolerated with no adverse events. Results indicate that krill oil could be more effective than fish oil in increasing n-3 PUFA, reducing n-6:n-3 PUFA ratio, and improving the omega-3 index. ClinicalTrials.gov, NCT01323036.
Effect of dietary supplementation of omega-3 polyunsaturated fatty acid (PUFA) rich fish oil on reproductive performance of the goat (Capra hircus).

PubMed

Mahla, Ajit Singh; Chaudhari, Ravjibhai K; Verma, Atul Kumar; Singh, Amit Kumar; Singh, Sanjay Kumar; Singh, Gyanendra; Sarkar, Mihir; Dutta, Narayan; Kumar, Harendra; Krishnaswamy, Narayanan

2017-09-01

Dietary supplementation of n-3 PUFA decreases the luteolytic PGF 2α and improves the pregnancy rate in the dairy cow. However, its effect in the goat is not known. Accordingly, we studied the effect of supplementation of n-3 PUFA rich Fish oil (FO) on different reproductive events in the goat. Cycling goats (n = 30) were divided into two equal groups and fed an isocaloric and isonitrogenous diet supplemented with either FO (TRT; n = 15) or palm oil (PO) (CON; n = 15) @ 0.6 mL/kg body weight for 72 days during the breeding season. Estrus synchronization was done on day 25 and 36 of supplementation using two PG regimen and the goats in estrus were bred. Mean interval from PGF 2α administration to the onset of estrus was 12 h longer (P < 0.05) in the TRT group than that of CON. The number of preovulatory follicles (POF) and ovulation rate was significantly higher in FO supplemented goats (P < 0.05) by 39.64 and 41.35%, respectively. Though the corpus luteum diameter was significantly higher (P < 0.05) on day 5, 8 and 11 post-breeding in the TRT group, mean serum progesterone (P 4 ) did not differ significantly (P > 0.05). Mean concentration of serum estradiol (E 2 ) was significantly (P < 0.01) lower in the FO supplemented group during day 0-60 post-breeding which could be due to significantly low serum cholesterol (P < 0.01). Though the serum concentration of PGF 2α metabolite (PGFM) and PGE 2 metabolite (PGEM) in the pregnant goats was significantly (P < 0.05) lower in the TRT group on day 16 and 17 post-breeding, the ratio of PGEM to PGFM remained unaffected suggesting a favourable effect of FO supplementation on the early pregnancy. The number of embryos, twinning rate and kidding rate were high in FO supplemented group though it was non-significant. However, gestation length, birth weight of kids and neonatal behaviour were comparable between the groups (P > 0.05). In conclusion, supplementation of n-3 PUFA rich FO significantly
Regulation of Rat Hepatic L-Pyruvate Kinase Promoter Composition and Activity by Glucose, n-3 Polyunsaturated Fatty Acids, and Peroxisome Proliferator-activated Receptor-α Agonist*S

PubMed Central

Xu, Jinghua; Christian, Barbara; Jump, Donald B.

2009-01-01

Carbohydrate regulatory element-binding protein (ChREBP), MAX-like factor X(MLX), and hepatic nuclear factor-4α (HNF-4α)are key transcription factors involved in the glucose-mediated induction of hepatic L-type pyruvate kinase (L-PK) gene transcription. n-3 polyunsaturated fatty acids (PUFA) and WY14643 (peroxisome proliferator-activated receptor α (PPARα) agonist) interfere with glucose-stimulated L-PK gene transcription in vivo and in rat primary hepatocytes. Feeding rats a diet containing n-3 PUFA or WY14643 suppressed hepatic mRNAL-PK but did not suppress hepatic ChREBP or HNF-4α nuclear abundance. Hepatic MLX nuclear abundance, however, was suppressed by n-3 PUFA but not WY14643. In rat primary hepatocytes, glucose-stimulated accumulation of mRNALPK and L-PK promoter activity correlated with increased ChREBP nuclear abundance. This treatment also increased L-PK promoter occupancy by RNA polymerase II (RNA pol II), acetylated histone H3 (Ac-H3), and acetylated histone H4 (Ac-H4) but did not significantly impact L-PK promoter occupancy by ChREBP or HNF-4α. Inhibition of L-PK promoter activity by n-3 PUFA correlated with suppressed RNA pol II, Ac-H3, and Ac-H4 occupancy on the L-PK promoter. Although n-3 PUFA transiently suppressed ChREBP and MLX nuclear abundance, this treatment did not impact ChREBP-LPK promoter interaction. HNF4α-LPK promoter interaction was transiently suppressed by n-3 PUFA. Inhibition of L-PK promoter activity by WY14643 correlated with a transient decline in ChREBP nuclear abundance and decreased Ac-H4 interaction with the L-PK promoter. WY14643, however, had no impact on MLX nuclear abundance or HNF4α-LPK promoter interaction. Although overexpressed ChREBP or HNF-4α did not relieve n-3 PUFA suppression of L-PK gene expression, overexpressed MLX fully abrogated n-3 PUFA suppression of L-PK promoter activity and mRNAL-PK abundance. Overexpressed ChREBP, but not MLX, relieved the WY14643 inhibition of L-PK. In conclusion, n-3 PUFA
Effect of heat treatment on the n-3/n-6 ratio and content of polyunsaturated fatty acids in fish tissues.

PubMed

Schneedorferová, Ivana; Tomčala, Aleš; Valterová, Irena

2015-06-01

The aim of this study was to compare the effect of different heat treatments (pan-frying, oven-baking, and grilling) on the contents of polyunsaturated fatty acids (PUFAs) in fish tissue. Four fish species were examined: pike, carp, cod, and herring. High performance liquid chromatography, coupled with electrospray ionization and mass spectrometric detection (HPLC/ESI/MS), was employed for determination of intact lipid molecules containing n-3 and n-6 PUFAs. Although mostly non-polar lipids (triacylglycerols, TGs) were present in the fish tissue, the PUFAs were present preferentially in the phospholipid fraction. Omnivorous fish species (carp, herring) contained more TGs than did predatory ones (pike, cod). Higher amounts of PUFAs were detected in the marine species than in the freshwater ones. The impact of heat treatments on the lipid composition in the fish tissue seems to be species-specific, as indicated by multivariate data analysis. Herring tissue is most heat-stable, and the mildest heat treatment for PUFA preservation was oven-baking. Copyright © 2014 Elsevier Ltd. All rights reserved.
Effect of omega 3 and omega 6 fatty acid intakes from diet and supplements on plasma fatty acid levels in the first 3 years of life.

PubMed

Hoyos, Camilla; Almqvist, Catarina; Garden, Frances; Xuan, Wei; Oddy, Wendy H; Marks, Guy B; Webb, Karen L

2008-01-01

The optimal method for conducting omega (n-)3 polyunsaturated fatty acid (PUFA) supplementation trials in children is unknown. To assess the impact of n-3 and n-6 PUFA intake from the background diet on plasma levels of n-3 and n-6 PUFA in children aged 0-3 years, with and without n-3 supplementation. Subjects were randomised antenatally to receive either n-3 PUFA supplements and low n-6 PUFA cooking oils and spreads or a control intervention, designed to maintain usual fatty acid intake. Dietary intake was assessed at 18 months by 3-day weighed food record and at 3 years by food frequency questionnaire. Plasma phospholipids were measured at both time points. Associations were tested by regression. N-3 PUFA intake from background diet did not significantly affect plasma n-3 levels. In contrast, n-6 PUFA intake in background diet was positively related to plasma n-6 levels in both study groups. In addition, n-6 PUFA intake from diet was negatively associated with plasma n-3 levels at 18 months and 3 years (-0.16%/g n-6 intake, 95%CI -0.29 to -0.03 and -0.05%/g n-6 intake, 95%CI -0.09 to -0.01, respectively) in the active group, but not in the control group. Interventions intending to increase plasma n-3 PUFA in children by n-3 supplementation should also minimise n-6 PUFA intake in the background diet.
Umbilical cord PUFA are determined by maternal and child fatty acid desaturase (FADS) genetic variants in the Avon Longitudinal Study of Parents and Children (ALSPAC)

PubMed Central

Lattka, Eva; Koletzko, Berthold; Zeilinger, Sonja; Hibbeln, Joseph R.; Klopp, Norman; Ring, Susan M.; Steer, Colin D.

2012-01-01

Fetal supply with long-chain PUFA (LC-PUFA) during pregnancy is important for brain growth and visual and cognitive development and is provided by materno–fetal placental transfer. We recently showed that maternal fatty acid desaturase (FADS) genotypes modulate the amounts of LC-PUFA in maternal blood. Whether FADS genotypes influence the amounts of umbilical cord fatty acids has not been investigated until now. The aim of the present study was to investigate the influence of maternal and child FADS genotypes on the amounts of LC-PUFA in umbilical cord venous plasma as an indicator of fetal fatty acid supply during pregnancy. A total of eleven cord plasma n-6 and n-3 fatty acids were analysed for association with seventeen FADS gene cluster SNP in over 2000 mothers and children from the Avon Longitudinal Study of Parents and Children. In a multivariable analysis, the maternal genotype effect was adjusted for the child genotype and vice versa to estimate which of the two has the stronger influence on cord plasma fatty acids. Both maternal and child FADS genotypes and haplotypes influenced amounts of cord plasma LC-PUFA and fatty acid ratios. Specifically, most analysed maternal SNP were associated with cord plasma levels of the precursor n-6 PUFA, whereas the child genotypes were mainly associated with more highly desaturated n-6 LC-PUFA. This first study on FADS genotypes and cord fatty acids suggests that fetal LC-PUFA status is determined to some extent by fetal fatty acid conversion. Associations of particular haplotypes suggest specific effects of SNP rs498793 and rs968567 on fatty acid metabolism. PMID:22877655
Umbilical cord PUFA are determined by maternal and child fatty acid desaturase (FADS) genetic variants in the Avon Longitudinal Study of Parents and Children (ALSPAC).

PubMed

Lattka, Eva; Koletzko, Berthold; Zeilinger, Sonja; Hibbeln, Joseph R; Klopp, Norman; Ring, Susan M; Steer, Colin D

2013-04-14

Fetal supply with long-chain PUFA (LC-PUFA) during pregnancy is important for brain growth and visual and cognitive development and is provided by materno-fetal placental transfer. We recently showed that maternal fatty acid desaturase (FADS) genotypes modulate the amounts of LC-PUFA in maternal blood. Whether FADS genotypes influence the amounts of umbilical cord fatty acids has not been investigated until now. The aim of the present study was to investigate the influence of maternal and child FADS genotypes on the amounts of LC-PUFA in umbilical cord venous plasma as an indicator of fetal fatty acid supply during pregnancy. A total of eleven cord plasma n-6 and n-3 fatty acids were analysed for association with seventeen FADS gene cluster SNP in over 2000 mothers and children from the Avon Longitudinal Study of Parents and Children. In a multivariable analysis, the maternal genotype effect was adjusted for the child genotype and vice versa to estimate which of the two has the stronger influence on cord plasma fatty acids. Both maternal and child FADS genotypes and haplotypes influenced amounts of cord plasma LC-PUFA and fatty acid ratios. Specifically, most analysed maternal SNP were associated with cord plasma levels of the precursor n-6 PUFA, whereas the child genotypes were mainly associated with more highly desaturated n-6 LC-PUFA. This first study on FADS genotypes and cord fatty acids suggests that fetal LC-PUFA status is determined to some extent by fetal fatty acid conversion. Associations of particular haplotypes suggest specific effects of SNP rs498793 and rs968567 on fatty acid metabolism.
Dietary Echium Oil Increases Long-Chain n–3 PUFAs, Including Docosapentaenoic Acid, in Blood Fractions and Alters Biochemical Markers for Cardiovascular Disease Independently of Age, Sex, and Metabolic Syndrome12

PubMed Central

Kuhnt, Katrin; Fuhrmann, Claudia; Köhler, Melanie; Kiehntopf, Michael; Jahreis, Gerhard

2014-01-01

Dietary supplementation with echium oil (EO) containing stearidonic acid (SDA) is a plant-based strategy to improve long-chain (LC) n–3 (ω-3) polyunsaturated fatty acid (PUFA) status in humans. We investigated the effect of EO on LC n–3 PUFA accumulation in blood and biochemical markers with respect to age, sex, and metabolic syndrome. This double-blind, parallel-arm, randomized controlled study started with a 2-wk run-in period, during which participants (n = 80) were administered 17 g/d run-in oil. Normal-weight individuals from 2 age groups (20–35 and 49–69 y) were allotted to EO or fish oil (FO; control) groups. During the 8-wk intervention, participants were administered either 17 g/d EO (2 g SDA; n = 59) or FO [1.9 g eicosapentaenoic acid (EPA); n = 19]. Overweight individuals with metabolic syndrome (n = 19) were recruited for EO treatment only. During the 10-wk study, the participants followed a dietary n–3 PUFA restriction, e.g., no fish. After the 8-wk EO treatment, increases in the LC n–3 metabolites EPA (168% and 79%) and docosapentaenoic acid [DPA (68% and 39%)] were observed, whereas docosahexaenoic acid (DHA) decreased (−5% and −23%) in plasma and peripheral blood mononuclear cells, respectively. Compared with FO, the efficacy of EO to increase EPA and DPA in blood was significantly lower (∼25% and ∼50%, respectively). A higher body mass index (BMI) was associated with lower relative and net increases in EPA and DPA. Compared with baseline, EO significantly reduced serum cholesterol, LDL cholesterol, oxidized LDL, and triglyceride (TG), but also HDL cholesterol, regardless of age and BMI. In the FO group, only TG decreased. Overall, daily intake of 15–20 g EO increased EPA and DPA in blood but had no influence on DHA. EO lowered cardiovascular risk markers, e.g., serum TG, which is particularly relevant for individuals with metabolic syndrome. Natural EO could be a noteworthy source of n–3 PUFA in human nutrition. This trial
Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease

PubMed Central

Knott, L.; Avery, N.C.; Hollander, A.P.; Tarlton, J.F.

2011-01-01

Summary Objective To examine effects of high omega-3 (n-3) polyunsaturated fatty acid (PUFA) diets on development of osteoarthritis (OA) in a spontaneous guinea pig model, and to further characterise pathogenesis in this model. Modern diets low in n-3 PUFAs have been linked with increases in inflammatory disorders, possibly including OA. However, n-3 is also thought to increases bone density, which is a possible contributing factor in OA. Therefore we aim to determine the net influence of n-3 in disease development. Method OA-prone Dunkin-Hartley (DH) Guinea pigs were compared with OA-resistant Bristol Strain-2s (BS2) each fed a standard or an n-3 diet from 10 to 30 weeks (10/group). We examined cartilage and subchondral bone pathology by histology, and biochemistry, including collagen cross-links, matrix metalloproteinases (MMPs), alkaline phosphatase, glycosaminoglycan (GAG), and denatured type II collagen. Results Dietary n-3 reduced disease in OA-prone animals. Most cartilage parameters were modified by n-3 diet towards those seen in the non-pathological BS2 strain – significantly active MMP-2, lysyl-pyridinoline and total collagen cross-links – the only exception being pro MMP-9 which was lower in the BS2, yet increased with n-3. GAG content was higher and denatured type II lower in the n-3 group. Subchondral bone parameters in the DH n-3 group also changed towards those seen in the non-pathological strain, significantly calcium:phosphate ratios and epiphyseal bone density. Conclusion Dietary n-3 PUFA reduced OA in the prone strain, and most disease markers were modified towards those of the non-OA strain, though not all significantly so. Omega-3 did not increase markers of pathology in either strain. PMID:21723952
Lipid Emulsion Enriched in Omega-3 PUFA Accelerates Wound Healing: A Placebo-Controlled Animal Study.

PubMed

Peng, Yi-Chi; Yang, Fwu-Lin; Subeq, Yi-Maun; Tien, Chin-Chieh; Chao, Yann-Fen C; Lee, Ru-Ping

2018-06-01

The Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) generate bioactive lipid mediators that reduce inflammation. The present study evaluated the effect of SMOFlipid containing ω-3 PUFAs on wound healing. Rats were divided into a SMOFlipid (SMOF) group and a 0.9% saline (placebo) group, with eight rats in each group. Wound excision was performed on the dorsal surface of each rat. In the SMOF group, 1 gm/kg SMOFlipid was dissolved in 3 mL saline as a treatment; in the placebo group, 3 mL saline was prepared as a treatment. The treatments were administered intravenously at an initial rate of 0.2 mL/kg body weight/h immediately after wounding, for 72 h. Blood samples were collected for white blood cell, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 measurements at the baseline and at 1, 6, 12, 24, 48, and 72 h after intervention. Wound areas were measured over a 2-week period after excision, and a histological examination was performed. Compared with the placebo group, SMOFlipid supplementation engendered significant decreases in the wound area on day 3 (78.28 ± 5.25 vs. 105.86 ± 8.89%), day 5 (72.20 ± 4.31 vs. 96.39 ± 4.72%), day 10 (20.78 ± 1.28 vs. 39.80 ± 10.38%), and day 14 (7.56 ± 0.61 vs. 15.10 ± 2.42%). The placebo group had a higher TNF-α level than the SMOF group at 72 h. The IL-10 level was higher in the SMOF group than in the placebo group at 48 h. Histological analysis revealed a higher rate of fibroblast distribution and collagen fiber organization in the SMOF group (P = 0.01). SMOFlipid enriched in ω-3 PUFA accelerates wound healing.
Dietary intake of fish and n-3 polyunsaturated fatty acids and risks of perinatal depression: The Japan Environment and Children's Study (JECS).

PubMed

Hamazaki, Kei; Takamori, Ayako; Tsuchida, Akiko; Kigawa, Mika; Tanaka, Tomomi; Ito, Mika; Adachi, Yuichi; Saito, Shigeru; Origasa, Hideki; Inadera, Hidekuni

2018-03-01

The results of several epidemiological studies and clinical trials investigating the effects of n-3 polyunsaturated fatty acids (PUFAs) on antenatal and postnatal depression remain controversial. We investigated the possible association of dietary intake of fish and n-3 PUFAs with the risks of maternal and paternal psychological distress during pregnancy and of maternal postpartum depression in Japan. From a dataset comprising 104,102 maternal registrations and 52,426 paternal registrations in The Japan Environment and Children's Study, this study analyzed complete data on questionnaires for 75,139, 79,346, and 77,661 women during early pregnancy, mid-late pregnancy, and after pregnancy, respectively, and for 41,506 male partners. Multivariable logistic regression showed reduced risk of psychological distress in the second and third quintiles for fish intake in early pregnancy and in the second to fifth quintile in mid-late pregnancy. No reductions were observed for n-3 PUFA intake in early pregnancy but in the second to fourth quintile in mid-late pregnancy. For postpartum depression, reductions were observed in the second to fourth quintile for fish intake but only in the first quintile for n-3 PUFA intake. As for paternal psychological distress, only the fourth quintile for fish intake showed a significant reduced risk but none were shown for n-3 PUFA intake. In conclusion, fish intake was associated with some reduced risk of psychological distress during pregnancy, even for male partners. The associations were weaker for n-3 PUFA intake than for fish intake. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Microencapsulated krill and tuna oil blend raises plasma long-chain n-3 polyunsaturated fatty acid levels compared to tuna oil with similar increases in ileal contractility in rats.

PubMed

Patten, Glen S; Sanguansri, Luz; Augustin, Mary Ann; Abeywardena, Mahinda Y; Bird, Anthony R; Patch, Craig S; Belobrajdic, Damien P

2017-03-01

Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) may be more bioavailable from krill oil compared to fish oil due to their phospholipid structure. We tested whether a microencapsulated krill and tuna oil blend (ME-TOKO) provided greater LC n-3 PUFA bioavailability, improved blood lipid profiles and increased intestinal contractility compared to microencapsulated tuna oil (ME-TO). Rats were divided into three groups to receive isocaloric diets containing ME-TO, ME-TOKO and microencapsulated olive oil (ME-OO) at 0.3 or 2 g/100 g for 4 weeks. Final body and organ weights, feed intake and waste output were similar. ME-TOKO rats had higher plasma total LC n-3 PUFA levels compared to ME-TO, but liver LC n-3 PUFA levels and plasma triglyceride and cholesterol levels were similar in non-fasted rats. Diets containing 2% ME-TO and ME-TOKO also showed similar increases in ileal contractility. In summary, ME-TO bioavailability of LC n-3 PUFA was similar to ME-TOKO.
n-3 polyunsaturated fatty acid supplementation reduces insulin resistance in hepatitis C virus infected patients: a randomised controlled trial.

PubMed

Freire, T O; Boulhosa, R S S B; Oliveira, L P M; de Jesus, R P; Cavalcante, L N; Lemaire, D C; Toralles, M B P; Lyra, L G C; Lyra, A C

2016-06-01

Insulin resistance promotes liver disease progression and may be associated with a lower response rate in treated hepatitis C virus (HCV) infected patients. n-3 polyunsaturated fatty acid (PUFA) supplementation may reduce insulin resistance. The present study aimed to evaluate the effect of n-3 PUFA supplementation on insulin resistance in these patients. In a randomised, double-blind clinical trial, 154 patients were screened. After applying inclusion criteria, 52 patients [homeostasis model assessment index of insulin resistance (HOMA-IR ≥2.5)] were randomly divided into two groups: n-3 PUFA (n = 25/6000 mg day(-1) of fish oil) or control (n = 27/6000 mg day(-1) of soybean oil). Both groups were supplemented for 12 weeks and underwent monthly nutritional consultation. Biochemical tests were performed at baseline and after intervention. Statistical analysis was performed using the Wilcoxon Mann-Whitney test for comparisons and the Wilcoxon test for paired data. Statistical package r, version 3.02 (The R Project for Statistical Computing) was used and P < 0.05 (two-tailed) was considered statistically significant. Comparisons between groups showed that n-3 PUFA supplementation was more effective than the control for reducing HOMA-IR (P = 0.015) and serum insulin (P = 0.016). The n-3 PUFA group not only showed a significant reduction in HOMA-IR 3.8 (3.2-5.0) versus 2.4 (1.8-3.3) (P = 0.002); serum insulin 17.1 (13.8-20.6) μIU mL(-1) versus 10.9 (8.6-14.6) μIU mL(-1) (P = 0.001); and glycated haemoglobin 5.4% (5.0-5.7%) versus 5.1% (4.8-5.6%) (P = 0.011), but also presented an increase in interleukin-1 97.5 (0.0-199.8) pg mL(-1) versus 192.4 (102.2-266.8) pg mL(-1) (P = 0.003) and tumour necrosis factor 121.2 (0.0-171.3) pg mL(-1) versus 185.7 (98.0-246.9) pg mL(-1) (P = 0.003). n-3 PUFA supplementation reduces insulin resistance in genotype 1 HCV infected patients. © 2015 The British Dietetic Association Ltd.
Effect of caloric restriction with or without n-3 polyunsaturated fatty acids on insulin sensitivity in obese subjects: A randomized placebo controlled trial.

PubMed

Razny, Urszula; Kiec-Wilk, Beata; Polus, Anna; Goralska, Joanna; Malczewska-Malec, Malgorzata; Wnek, Dominika; Zdzienicka, Anna; Gruca, Anna; Childs, Caroline E; Kapusta, Maria; Slowinska-Solnica, Krystyna; Calder, Philip C; Dembinska-Kiec, Aldona

2015-12-01

Caloric restriction and n-3 polyunsaturated fatty acid (PUFA) supplementation protect from some of the metabolic complications. The aim of this study was to assess the influence of a low calorie diet with or without n-3 PUFA supplementation on glucose dependent insulinotropic polypeptide (GIP) output and insulin sensitivity markers in obese subjects. Obese, non-diabetic subjects (BMI 30-40 kg/m(2)) and aged 25-65 yr. were put on low calorie diet (1200-1500 kcal/day) supplemented with either 1.8 g/day n-3 PUFA (DHA/EPA, 5:1) (n = 24) or placebo capsules (n = 24) for three months in a randomized placebo controlled trial. Insulin resistance markers and GIP levels were analysed from samples obtained at fasting and during an oral glucose tolerance test (OGTT). Caloric restriction with n-3 PUFA led to a decrease of insulin resistance index (HOMA-IR) and a significant reduction of insulin output as well as decreased GIP secretion during the OGTT. These effects were not seen with caloric restriction alone. Changes in GIP output were inversely associated with changes in red blood cell EPA content whereas fasting GIP level positively correlated with HOMA-IR index. Blood triglyceride level was lowered by caloric restriction with a greater effect when n-3 PUFA were included and correlated positively with fasting GIP level. Three months of caloric restriction with DHA + EPA supplementation exerts beneficial effects on insulin resistance, GIP and triglycerides. Combining caloric restriction and n-3 PUFA improves insulin sensitivity, which may be related to a decrease of GIP levels.
Differences in omega-3 and omega-6 polyunsaturated fatty acid consumption in people at ultra-high risk of psychosis, first-episode schizophrenia, and in healthy controls.

PubMed

Pawełczyk, Tomasz; Trafalska, Elżbieta; Pawełczyk, Agnieszka; Kotlicka-Antczak, Magdalena

2017-12-01

Supplementation with omega-3 PUFA showed efficacy in reducing the risk of transition into psychosis in UHR individuals. It is uncertain whether dietary patterns can be partly responsible for n-3 deficiencies observed in susceptible participants before the diagnosis of schizophrenia. The study was designed to assess differences in omega-3 and omega-6 PUFA consumption in healthy controls (HC), UHR participants and FES patients as well as to verify the hypothesis that dietary changes in PUFA consumption are present before active psychosis develops, that is, in UHR individuals. Dietary habits during the previous year were assessed in 34 patients at UHR of psychosis, 33 patients diagnosed with FES and 33 HC participants using a validated Food-Frequency Questionnaire and the Polish Food Composition Tables. Significant differences in omega-3 and omega-6 PUFA intake were observed between study groups. UHR and FES groups reported significantly higher consumption of omega-6 PUFA in comparison with HC. FES patients also reported a higher consumption of alpha-linolenic acid (omega-3) in comparison with HC. No significant differences were seen in consumption of long-chain marine PUFA. Differences in omega-6 and omega-3 PUFA consumption exist before development of psychotic symptoms, fulfilling the criteria of schizophrenia. © 2015 Wiley Publishing Asia Pty Ltd.
Association between very long chain fatty acids in the meibomian gland and dry eye resulting from n-3 fatty acid deficiency.

PubMed

Tanaka, Hideko; Harauma, Akiko; Takimoto, Mao; Moriguchi, Toru

2015-06-01

In our previously study, we reported lower tear volume in with an n-3 fatty acid deficient mice and that the docosahexaenoic acid and total n-3 fatty acid levels in these mice are significantly reduced in the meibomian gland, which secretes an oily tear product. Furthermore, we noted very long chain fatty acids (≥25 carbons) in the meibomian gland. To verify the detailed mechanism of the low tear volume in the n-3 fatty acid-deficient mice, we identified the very long chain fatty acids in the meibomian gland, measured the fatty acid composition in the tear product. Very long chain fatty acids were found to exist as monoesters. In particular, very long chain fatty acids with 25-29 carbons existed for the most part as iso or anteiso branched-chain fatty acids. n-3 fatty acid deficiency was decreased the amount of meibum secretion from meibomian gland without change of fatty acid composition. These results suggest that the n-3 fatty acid deficiency causes the enhancement of evaporation of tear film by reducing oily tear secretion along with the decrease of meibomian gland function. Copyright © 2015 Elsevier Ltd. All rights reserved.
Cardiometabolic risk factors are influenced by Stearoyl-CoA Desaturase (SCD) -1 gene polymorphisms and n-3 polyunsaturated fatty acid supplementation.

PubMed

Rudkowska, Iwona; Julien, Pierre; Couture, Patrick; Lemieux, Simone; Tchernof, André; Barbier, Olivier; Vohl, Marie-Claude

2014-05-01

To determine if single nucleotide polymorphisms (SNPs) in stearoyl-CoA desaturase (SCD)-1 gene that encodes a key enzyme for fatty acid metabolism are associated with the response of cardiometabolic risk factors to n-3 PUFA supplementation. Two hundred and ten subjects completed a 2-week run-in period followed by 6-week supplementation with 5 g of fish oil (1.9-2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid). Risk factors were measured pre and post n-3 supplementation. Fatty acid composition of plasma phospholipids was analyzed by GC and the desaturase indices SCD16 (16:1n-7/16:0) and SCD18 (18:1n-9/18:0) were calculated. Genotyping of eight SNPs of the SCD1 gene was performed. N-3 PUFA supplementation decreased plasma triglycerides, as well as SCD16 and SCD18 indices, but increased fasting plasma glucose concentrations. SNPs in SCD1-modified cardiometabolic risk factors pre and post n-3 PUFA supplementation: triglyceride (rs508384, p = 0.0086), IL6 (rs3071, p = 0.0485), C-reactive protein (rs3829160, p = 0.0489), and SCD18 indices (rs2234970, p = 0.0337). A significant interaction effect between the SNP and n-3 PUFA supplementation was also observed for fasting plasma glucose levels (rs508384, p = 0.0262). These results suggest that cardiometabolic risk factors are modulated by genetic variations in the SCD1 gene alone or in combination with n-3 PUFA supplementation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Reversed-phase high-performance liquid chromatography purification of methyl esters of C(16)-C(28) polyunsaturated fatty acids in microalgae, including octacosaoctaenoic acid [28:8(n-3)].

PubMed

Mansour, Maged P

2005-12-02

A preparative reversed-phase (RP; C(18)) high-performance liquid chromatography (HPLC) method with gradient elution using acetonitrile (MeCN)-chloroform (CHCl(3)) (or dichloromethane (DCM)) and evaporative light-scattering detection (ELSD) with automatic multiple injection and fraction collection was used to purify milligram quantities of microalgal polyunsaturated fatty acids (PUFA), separated as methyl esters (ME). PUFA-ME purified included methyl esters of docosahexaenoic acid (DHA; 22:6(n-3)), eicosapentaenoic acid (EPA; 20:5(n-3)) and the unusual very long-chain (C(28)) highly unsaturated fatty acid (VLC-HUFA), octacosaoctaenoic acid [28:8(n-3)(4, 7, 10, 13, 16, 19, 22, 25)] from the marine dinoflagellate Scrippsiella sp. CS-295/c. Other PUFA purified from various microalgae using this RP-HPLC method to greater than 95% purity included 16:3(n-4), 16:4(n-3), 16:4(n-1) and 18:5(n-3). The number of injections required was variable and depended on the abundance of the desired PUFA-ME, and resolution from closely eluting PUFA-ME, which determined the maximum loading. The purity of these fatty acids was determined by electron impact (EI) GC-MS and the chain length and location of double bonds was determined by EI GC-MS of 4,4-dimethyl oxazoline (DMOX) derivatives formed using a low temperature method. Advantages over silver-ion HPLC for purifying PUFA-ME is that separation occurs according to chain length as well as degree of unsaturation enabling separation of PUFA-ME with the same degree of unsaturation but different chain length (i.e. between 18:5(n-3) and 20:5(n-3)). In addition, PUFA-ME are not strongly adsorbed, but elute earlier than their more saturated corresponding FAME of the same chain length. This method is robust, simple, and requires only a short re-equilibration time. It is a useful tool for preparing milligram quantities of pure PUFA-ME for bioactive screening (as free fatty acids), although many multiple injections may be required for minor PUFA

Balancing the benefits of n-3 polyunsaturated fatty acids and the risks of methylmercury exposure from fish consumption

PubMed Central

Mahaffey, Kathryn R; Sunderland, Elsie M; Chan, Hing Man; Choi, Anna L; Grandjean, Philippe; Mariën, Koenraad; Oken, Emily; Sakamoto, Mineshi; Schoeny, Rita; Weihe, Pál; Yan, Chong-Huai; Yasutake, Akira

2011-01-01

Fish and shellfish are widely available foods that provide important nutrients, particularly n-3 polyunsaturated fatty acids (n-3 PUFAs), to many populations globally. These nutrients, especially docosahexaenoic acid, confer benefits to brain and visual system development in infants and reduce risks of certain forms of heart disease in adults. However, fish and shellfish can also be a major source of methylmercury (MeHg), a known neurotoxicant that is particularly harmful to fetal brain development. This review documents the latest knowledge on the risks and benefits of seafood consumption for perinatal development of infants. It is possible to choose fish species that are both high in n-3 PUFAs and low in MeHg. A framework for providing dietary advice for women of childbearing age on how to maximize the dietary intake of n-3 PUFAs while minimizing MeHg exposures is suggested. PMID:21884130
Rapid effects of essential fatty acid deficiency on growth and development parameters and transcription of key fatty acid metabolism genes in juvenile barramundi (Lates calcarifer).

PubMed

Salini, Michael J; Turchini, Giovanni M; Wade, Nicholas M; Glencross, Brett D

2015-12-14

Barramundi (Lates calcarifer), a catadromous teleost of significant and growing commercial importance, are reported to have limited fatty acid bioconversion capability and therefore require preformed long-chain PUFA (LC-PUFA) as dietary essential fatty acid (EFA). In this study, the response of juvenile barramundi (47·0 g/fish initial weight) fed isolipidic and isoenergetic diets with 8·2% added oil was tested. The experimental test diets were either devoid of fish oil (FO), and thus with no n-3 LC-PUFA (FO FREE diet), or with a low inclusion of FO (FO LOW diet). These were compared against a control diet containing only FO (FO CTRL diet) as the added lipid source, over an 8-week period. Interim samples and measurements were taken fortnightly during the trial in order to define the aetiology of the onset and progression of EFA deficiency. After 2 weeks, the fish fed the FO FREE and FO LOW diets had significantly lower live-weights, and after 8 weeks significant differences were detected for all performance parameters. The fish fed the FO FREE diet also had a significantly higher incidence of external abnormalities. The transcription of several genes involved in fatty acid metabolism was affected after 2 weeks of feeding, showing a rapid nutritional regulation. This experiment documents the aetiology of the onset and the progression of EFA deficiency in juvenile barramundi and demonstrates that such deficiencies can be detected within 2 weeks in juvenile fish.
Effect of Omega-3 PUFAs Supplementation with Lifestyle Modification on Anthropometric Indices and Vo2 max in Overweight Women.

PubMed

Haghravan, Simin; Keshavarz, Seyed Ali; Mazaheri, Reza; Alizadeh, Zahra; Mansournia, Mohammad Ali

2016-05-01

Despite the fact that the recommendations of counteracting obesity advocate for changing lifestyle and physical activity habits, the prevalence of obesity continues to rise. The aim of the study was to investigate the effect of omega-3 PUFAs supplementation with lifestyle modification on anthropometric indices and Vo2max in overweight women. Fifty overweight women aged between 20 to 45 years were recruited in this interventional study. Women randomly were divided into two experimental groups (n = 25). Group 1 received omega-3 supplement, aerobic exercise program, and a healthy diet education. Group 2 was similar to group 1, except in that patients received placebo instead of omega-3 capsules. Experimental and placebo group subjects were asked to take one supplementary capsule every day, for 8 weeks. Anthropometric indices were measured in the fourth and eighth weeks of the trial. The maximum aerobic capacity (Vo2max) was determined using a gas analysis device. The level of significance for comparing the results before and after the trial was considered at P < 0.05. According to the data, body weight, body fat percentage, waist circumference, and abdominal skinfold thickness significantly reduced in the omega-3 treated group compared to the control group during 8 weeks after the initiation of the study (P < 0.05). In addition, supplementation of omega-3, significantly improved the VO2max outcome compared to that of the control group (P = 0.03). According to the results, it seems that omega-3 PUFAS supplementation with lifestyle modification has positive effects on anthropometric indices and Vo2max in overweight women.
PUFA-induced cell death is mediated by Yca1p-dependent and -independent pathways, and is reduced by vitamin C in yeast.

PubMed

Johansson, Magnus; Chen, Xin; Milanova, Stefina; Santos, Cristiano; Petranovic, Dina

2016-03-01

Polyunsaturated fatty acids (PUFA) such as linoleic acid (LA, n-6, C18:2) and γ-linolenic acid (GLA, n-6, C18:3) are essential and must be obtained from the diet. There has been a growing interest in establishing a bio-sustainable production of PUFA in several microorganisms, e.g. in yeast Saccharomyces cerevisiae. However, PUFAs can also be toxic to cells because of their susceptibility to peroxidation. Here we investigated the negative effects of LA and GLA production on S. cerevisiae by characterizing a strain expressing active Δ6 and Δ12 desaturases from the fungus Mucor rouxii. Previously, we showed that the PUFA-producing strain has low viability, down-regulated genes for oxidative stress response, and decreased proteasome activity. Here we show that the PUFA strain accumulates high levels of reactive oxygen species (ROS) and lipid peroxides, and accumulates damaged proteins. The PUFA strain also showed great increase in metacaspase Yca1p activity, suggesting cells could die by caspase-mediated cell death. When treated with antioxidant vitamin C, ROS, lipid peroxidation and protein carbonylation were greatly reduced, and the activity of the metacaspase was significantly decreased too, ultimately doubling the lifespan of the PUFA strain. When deleting YCA1, the caspase-like activity and the oxidative stress decreased and although the lifespan was slightly prolonged, the phenotype could not be fully reversed, pointing that Yca1p was not the main executor of cell death. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Effect of Marine-Derived n-3 Polyunsaturated Fatty Acids on C-Reactive Protein, Interleukin 6 and Tumor Necrosis Factor α: A Meta-Analysis

PubMed Central

Li, Kelei; Huang, Tao; Zheng, Jusheng; Wu, Kejian; Li, Duo

2014-01-01

Background Previous studies did not draw a consistent conclusion about the effects of marine-derived n-3 polyunsaturated fatty acids (PUFAs) on fasting blood level of C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). Methods and Findings A comprehensive search of Web of Science, PubMed, Embase and Medline (from 1950 to 2013) and bibliographies of relevant articles was undertaken. Sixty-eight RCTs with a total of 4601 subjects were included in the meta-analysis. Marine-derived n-3 PUFAs supplementation showed a lowering effect on Marine-derived n-3 PUFAs supplementation had a significant lowering effect on TNF-α, IL-6 and CRP in three groups of subjects (subjects with chronic non-autoimmune disease, subjects with chronic autoimmune disease and healthy subjects). A significant negative linear relationship between duration and effect size of marine-derived n-3 PUFAs supplementation on fasting blood levels of TNF-α and IL-6 in subjects with chronic non-autoimmune disease was observed, indicating that longer duration of supplementation could lead to a greater lowering effect. A similar linear relationship was also observed for IL-6 levels in healthy subjects. Restricted cubic spline analysis and subgroup analysis showed that the lowering effect of marine-derived n-3 PUFAs on CRP, IL-6 and TNF-α in subjects with chronic non-autoimmune disease became weakened when body mass index was greater than 30 kg/m2. The effect of marine-derived n-3 PUFAs from dietary intake was only assessed in subjects with chronic non-autoimmune disease, and a significant lowering effect was observed on IL-6, but not on CRP and TNF-α. Conclusions Marine-derived n-3 PUFAs supplementation had a significant lowering effect on CRP, IL-6 and TNF-α level. The lowering effect was most effective in non-obese subjects and consecutive long-term supplementation was recommended. PMID:24505395
Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs

PubMed Central

Galano, Jean-Marie; Guerranti, Roberto; Rossi, Marcello; Ciccoli, Lucia; Hayek, Joussef

2015-01-01

An involvement of the immune system has been suggested in Rett syndrome (RTT), a devastating neurodevelopmental disorder related to oxidative stress, and caused by a mutation in the methyl-CpG binding protein 2 gene (MECP2) or, more rarely, cyclin-dependent kinase-like 5 (CDKL5). To date, it is unclear whether both mutations may have an impact on the circulating cytokine patterns. In the present study, cytokines involved in the Th1-, Th2-, and T regulatory (T-reg) response, as well as chemokines, were investigated in MECP2- (MECP2-RTT) (n = 16) and CDKL5-Rett syndrome (CDKL5-RTT) (n = 8), before and after ω-3 polyunsaturated fatty acids (PUFAs) supplementation. A major cytokine dysregulation was evidenced in untreated RTT patients. In MECP2-RTT, a Th2-shifted balance was evidenced, whereas in CDKL5-RTT both Th1- and Th2-related cytokines (except for IL-4) were upregulated. In MECP2-RTT, decreased levels of IL-22 were observed, whereas increased IL-22 and T-reg cytokine levels were evidenced in CDKL5-RTT. Chemokines were unchanged. The cytokine dysregulation was proportional to clinical severity, inflammatory status, and redox imbalance. Omega-3 PUFAs partially counterbalanced cytokine changes, as well as aberrant redox homeostasis and the inflammatory status. RTT is associated with a subclinical immune dysregulation as the likely consequence of a defective inflammation regulatory signaling system. PMID:26236424
Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs.

PubMed

Leoncini, Silvia; De Felice, Claudio; Signorini, Cinzia; Zollo, Gloria; Cortelazzo, Alessio; Durand, Thierry; Galano, Jean-Marie; Guerranti, Roberto; Rossi, Marcello; Ciccoli, Lucia; Hayek, Joussef

2015-01-01

An involvement of the immune system has been suggested in Rett syndrome (RTT), a devastating neurodevelopmental disorder related to oxidative stress, and caused by a mutation in the methyl-CpG binding protein 2 gene (MECP2) or, more rarely, cyclin-dependent kinase-like 5 (CDKL5). To date, it is unclear whether both mutations may have an impact on the circulating cytokine patterns. In the present study, cytokines involved in the Th1-, Th2-, and T regulatory (T-reg) response, as well as chemokines, were investigated in MECP2- (MECP2-RTT) (n = 16) and CDKL5-Rett syndrome (CDKL5-RTT) (n = 8), before and after ω-3 polyunsaturated fatty acids (PUFAs) supplementation. A major cytokine dysregulation was evidenced in untreated RTT patients. In MECP2-RTT, a Th2-shifted balance was evidenced, whereas in CDKL5-RTT both Th1- and Th2-related cytokines (except for IL-4) were upregulated. In MECP2-RTT, decreased levels of IL-22 were observed, whereas increased IL-22 and T-reg cytokine levels were evidenced in CDKL5-RTT. Chemokines were unchanged. The cytokine dysregulation was proportional to clinical severity, inflammatory status, and redox imbalance. Omega-3 PUFAs partially counterbalanced cytokine changes, as well as aberrant redox homeostasis and the inflammatory status. RTT is associated with a subclinical immune dysregulation as the likely consequence of a defective inflammation regulatory signaling system.
Diet-Gene Interactions and PUFA Metabolism: A Potential Contributor to Health Disparities and Human Diseases

PubMed Central

Chilton, Floyd H.; Murphy, Robert C.; Wilson, Bryan A.; Sergeant, Susan; Ainsworth, Hannah; Seeds, Michael C.; Mathias, Rasika A.

2014-01-01

The “modern western” diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations. PMID:24853887
Polymorphisms in stearoyl coa desaturase and sterol regulatory element binding protein interact with N-3 polyunsaturated fatty acid intake to modify associations with anthropometric variables and metabolic phenotypes in Yup'ik people.

PubMed

Lemas, Dominick J; Klimentidis, Yann C; Aslibekyan, Stella; Wiener, Howard W; O'Brien, Diane M; Hopkins, Scarlett E; Stanhope, Kimber L; Havel, Peter J; Allison, David B; Fernandez, Jose R; Tiwari, Hemant K; Boyer, Bert B

2016-12-01

n-3 polyunsaturated fatty acid (n-3 PUFA) intake is associated with protection from obesity; however, the mechanisms of protection remain poorly characterized. The stearoyl CoA desaturase (SCD), insulin-sensitive glucose transporter (SLC2A4), and sterol regulatory element binding protein (SREBF1) genes are transcriptionally regulated by n-3 PUFA intake and harbor polymorphisms associated with obesity. The present study investigated how consumption of n-3 PUFA modifies associations between SCD, SLC2A4, and SREBF1 polymorphisms and anthropometric variables and metabolic phenotypes. Anthropometric variables and metabolic phenotypes were measured in a cross-sectional sample of Yup'ik individuals (n = 1135) and 33 polymorphisms were tested for main effects and interactions using linear models that account for familial correlations. n-3 PUFA intake was estimated using red blood cell nitrogen stable isotope ratios. SCD polymorphisms were associated with ApoA1 concentration and n-3 PUFA interactions with SCD polymorphisms were associated with reduced fasting cholesterol levels and waist-to-hip ratio. SLC2A4 polymorphisms were associated with hip circumference, high-density lipoprotein and ApoA1 concentrations. SREBF1 polymorphisms were associated with low-density lipoprotein and HOMA-IR and n-3 PUFA interactions were associated with reduced fasting insulin and HOMA-IR levels. The results suggest that an individual's genotype may interact with dietary n-3 PUFAs in ways that are associated with protection from obesity-related diseases in Yup'ik people. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Protective effect of dietary long-chain n-3 polyunsaturated fatty acids on bone loss in gonad-intact middle-aged male rats.

PubMed

Shen, Chwan-Li; Yeh, James K; Rasty, Jahan; Li, Yong; Watkins, Bruce A

2006-03-01

This study evaluated the effect of a fat blend containing long-chain (LC) n-3 PUFA on bone mineral density (BMD) and bone metabolism in gonad-intact middle-aged male rats (12 months old, n 28). Seven rats were killed on day 0 of dietary intervention to determine the baseline BMD. The remaining rats (seven per group) were fed a diet with one of the following dietary lipid treatments (g/kg diet): 167 g safflower oil + 33 g menhaden oil (N6 + N3 diet, control), 200 g safflower oil (N6 diet, almost devoid of LC n-3 PUFA), or 190 g menhaden oil + 10 g corn oil (N3 diet, rich in LC n-3 PUFA) for 20 weeks. After 20 weeks, all dietary treatment groups had a lower BMD compared with the baseline reference. However, rats fed the N3 diet had the highest bone mineral content and cortical + subcortical BMD compared with those fed the N6 and control N6 + N3 diet. Compared with the control (N6 + N3) group, rats fed the N3 diet had higher values for serum insulin-like growth factor-I, parathyroid hormone, 1,25-(OH)2 vitamin D3 and bone-specific alkaline phosphatase activity, but lower bone NO production and urinary Ca, whereas rats fed the N6 diet had higher bone prostaglandin E2 production and serum pyridinoline. These findings indicate a protective action of LC n-3 PUFA on ageing-induced bone loss in gonad-intact middle-aged male rats through a modulation of local factors and systemic calcitrophic hormones.
Dietary n-3 long chain polyunsaturated fatty acids in allergy prevention and asthma treatment.

PubMed

Willemsen, Linette E M

2016-08-15

The rise in non-communicable diseases, such as allergies, in westernized countries links to changes in lifestyle and diet. N-3 long chain polyunsaturated fatty acids (LCPUFA) present in marine oils facilitate a favorable milieu for immune maturation and may contribute to allergy prevention. N-3 LCPUFA can suppress innate and adaptive immune activation and induce epigenetic changes. Murine studies convincingly show protective effects of fish oil, a source of n-3 LCPUFA, in food allergy and asthma models. Observational studies in human indicate that high dietary intake of n-3 LCPUFA and low intake of n-6 PUFA may protect against the development of allergic disease early in life. High n-6 PUFA intake is also associated with an increased asthma risk while n-3 LCPUFA may be protective and reduce symptoms. The quality of the marine oil used has impact on efficacy of allergy prevention and several observations link in particular n-3 LCPUFA DHA to allergy suppression. Randomized controlled trials indicate that optimal timing, duration and dosage of n-3 LC-PUFA is required to exert an allergy protective effect. Supplementation during early pregnancy and lactation has shown promising results regarding allergy prevention. However these findings should be confirmed in a larger cohort. Although clinical trials in asthma patients reveal no consistent clinical benefits of n-3 LCPUFA supplementation on lung function, it can suppress airway inflammation. Future food-pharma approaches may reveal whether adjunct therapy with dietary n-3 LCPUFA can improve allergy prevention or immunotherapy via support of allergen specific oral tolerance induction or contribute to the efficacy of drug therapy for asthma patients. Copyright © 2016 Elsevier B.V. All rights reserved.
Polymorphisms in stearoyl CoA desaturase and sterol regulatory element binding protein interact with N-3 polyunsaturated fatty acid intake to modify associations with anthropometric variables and metabolic phenotypes in Yup'ik people

PubMed Central

Lemas, Dominick J.; Klimentidis, Yann C.; Aslibekyan, Stella; Wiener, Howard W.; O’Brien, Diane M.; Hopkins, Scarlett E.; Stanhope, Kimber L.; Havel, Peter J.; Allison, David B.; Fernandez, Jose R.; Tiwari, Hemant K.; Boyer, Bert B.

2016-01-01

Scope n-3 polyunsaturated fatty acid (n-3 PUFA) intake is associated with protection from obesity, however, the mechanisms of protection remain poorly characterized. The stearoyl CoA desaturase (SCD), insulin sensitive glucose transporter (SLC2A4), and sterol regulatory element binding protein (SREBF1) genes are transcriptionally regulated by n-3 PUFA intake and harbor polymorphisms associated with obesity. The present study investigated how consumption of n-3 PUFA modifies associations between SCD, SLC2A4, and SREBF1 polymorphisms and anthropometric variables and metabolic phenotypes. Materials and Methods Anthropometric variables and metabolic phenotypes were measured in a cross-sectional sample of Yup’ik individuals (n=1135) and thirty-three polymorphisms were tested for main effects and interactions using linear models that account for familial correlations. n-3 PUFA intake was estimated using red blood cell nitrogen stable isotope ratios. SCD polymorphisms were associated with ApoA1 concentration and n-3 PUFA interactions with SCD polymorphisms were associated with reduced fasting cholesterol levels and waist-to-hip ratio. SLC2A4 polymorphisms were associated with hip circumference, high-density lipoprotein and ApoA1 concentrations. SREBF1 polymorphisms were associated with low-density lipoprotein and HOMA-IR and n-3 PUFA interactions were associated with reduced fasting insulin and HOMA-IR levels. Conclusion These results suggest that an individual’s genotype may interact with dietary n-3 PUFAs in ways that are associated with protection from obesity-related diseases in Yup’ik people. PMID:27467133
Dietary Omega-3 Fatty Acids Prevented Adipocyte Hypertrophy by Downregulating DGAT-2 and FABP-4 in a Sex-Dependent Fashion.

PubMed

Balogun, Kayode A; Cheema, Sukhinder K

2016-01-01

Obesity is characterized by an increase in fat mass primarily as a result of adipocyte hypertrophy. Diets enriched in omega (n)-3 polyunsaturated fatty acids (PUFA) are suggested to reduce obesity, however, the mechanisms are not well understood. We investigated the effect of n-3 PUFA on adipocyte hypertrophy and the key genes involved in adipocyte hypertrophy. Female C57BL/6 mice were fed semi-purified diets (20 % w/w fat) containing high n-3 PUFA before mating, during pregnancy, and until weaning. Male and female offspring were continued on high n-3 PUFA (10 % w/w), medium n-3 PUFA (4 % w/w), or low n-3 PUFA (2 % w/w) diet for 16 weeks postweaning. Adipocyte area was quantified using microscopy, and gonadal mRNA expression of acyl CoA:diacylglycerol acyltransferase-2 (DGAT-2), fatty acid binding protein-4 (FABP-4) and leptin were measured. The high n-3 PUFA group showed higher levels of total n-3 PUFA in gonadal TAG compared to the medium and low n-3 PUFA groups (P < 0.001). The high n-3 PUFA male group had a lower adipocyte area compared to the medium and low n-3 PUFA group (P < 0.001); however, no difference was observed in females. The high n-3 PUFA male group showed lower mRNA expression of FABP-4, DGAT-2 and leptin compared to the low n-3 PUFA group, with no difference in females. Plasma lipid levels were lower in the high n-3 PUFA group compared to the other groups. Our findings show for the first time that n-3 PUFA prevents adipocyte hypertrophy by downregulating FABP-4, DGAT-2 and leptin; the effects are however sex-specific.
Functional and Structural Benefits Induced by Omega-3 Polyunsaturated Fatty Acids During Aging

PubMed Central

Cutuli, Debora

2017-01-01

Background Omega-3 polyunsaturated fatty acids (n-3 PUFA) are structural components of the brain and are indispensable for neuronal membrane synthesis. Along with decline in cognition, decreased synaptic density and neuronal loss, normal aging is accompanied by a reduction in n-3 PUFA concentration in the brain in both humans and rodents. Recently, many clinical and experimental studies have demonstrated the importance of n-3 PUFA in counteracting neurodegeneration and age-related dysfunctions. Methods Methods: This review will focus on the neuroprotective effects of n-3 PUFA on cognitive impairment, neuroinflammation and neurodegeneration during normal aging. Multiple pathways of n-3 PUFA preventive action will be examined. Results Namely, n-3 PUFA have been shown to increase the levels of several signaling factors involved in synaptic plasticity, thus leading to the increase of dendritic spines and synapses as well as the enhancement of hippocampal neurogenesis even at old age. In elderly subjects n-3 PUFA exert anti-inflammatory effects associated with improved cognitive functions. Interestingly, growing evidence highlights n-3 PUFA efficacy in preventing the loss of both gray and white matter volume and integrity. Conclusion This review shows that n-3 PUFA are essential for a successful aging and appear as ideal cognitive enhancers to be implemented in nutritional interventions for the promotion of healthy aging. PMID:27306037
Functional and Structural Benefits Induced by Omega-3 Polyunsaturated Fatty Acids During Aging.

PubMed

Cutuli, Debora

2017-01-01

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are structural components of the brain and are indispensable for neuronal membrane synthesis. Along with decline in cognition, decreased synaptic density and neuronal loss, normal aging is accompanied by a reduction in n-3 PUFA concentration in the brain in both humans and rodents. Recently, many clinical and experimental studies have demonstrated the importance of n-3 PUFA in counteracting neurodegeneration and agerelated dysfunctions. This review will focus on the neuroprotective effects of n-3 PUFA on cognitive impairment, neuroinflammation and neurodegeneration during normal aging. Multiple pathways of n-3 PUFA preventive action will be examined. Namely, n-3 PUFA have been shown to increase the levels of several signaling factors involved in synaptic plasticity, thus leading to the increase of dendritic spines and synapses as well as the enhancement of hippocampal neurogenesis even at old age. In elderly subjects n-3 PUFA exert anti-inflammatory effects associated with improved cognitive functions. Interestingly, growing evidence highlights n-3 PUFA efficacy in preventing the loss of both gray and white matter volume and integrity. This review shows that n-3 PUFA are essential for a successful aging and appear as ideal cognitive enhancers to be implemented in nutritional interventions for the promotion of healthy aging. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Genetic variation in FADS genes is associated with maternal long-chain PUFA status but not with cognitive development of infants in a high fish-eating observational study.

PubMed

Yeates, Alison J; Love, Tanzy M; Engström, Karin; Mulhern, Maria S; McSorley, Emeir M; Grzesik, Katherine; Alhamdow, Ayman; Wahlberg, Karin; Thurston, Sally W; Davidson, Philip W; van Wijngaarden, Edwin; Watson, Gene E; Shamlaye, Conrad F; Myers, G J; Strain, J J; Broberg, Karin

2015-12-01

Long-chain n-6 and n-3 PUFA (LC-PUFA), arachidonic acid (AA) (20:4n-6) and DHA (22:6n-3), are critical for optimal brain development. These fatty acids can be consumed directly from the diet, or synthesized endogenously from precursor PUFA by Δ-5 (encoded by FADS1) and Δ-6 desaturases (encoded by FADS2). The aim of this study was to determine the potential importance of maternal genetic variability in FADS1 and FADS2 genes to maternal LC-PUFA status and infant neurodevelopment in populations with high fish intakes. The Nutrition Cohorts 1 (NC1) and 2 (NC2) are longitudinal observational mother-child cohorts in the Republic of Seychelles. Maternal serum LC-PUFA was measured at 28 weeks gestation and genotyping for rs174537 (FADS1), rs174561 (FADS1), rs3834458 (FADS1-FADS2) and rs174575 (FADS2) was performed in both cohorts. The children completed the Bayley Scales of Infant Development II (BSID-II) at 30 months in NC1 and at 20 months in NC2. Complete data were available for 221 and 1310 mothers from NC1 and NC2 respectively. With increasing number of rs3834458 minor alleles, maternal concentrations of AA were significantly decreased (NC1 p=0.004; NC2 p<0.001) and precursor:product ratios for linoleic acid (LA) (18:2n-6)-to-AA (NC1 p<0.001; NC2 p<0.001) and α-linolenic acid (ALA) (18:3n-3)-to-DHA were increased (NC2 p=0.028). There were no significant associations between maternal FADS genotype and BSID-II scores in either cohort. A trend for improved PDI was found among infants born to mothers with the minor rs3834458 allele.In these high fish-eating cohorts, genetic variability in FADS genes was associated with maternal AA status measured in serum and a subtle association of the FADS genotype was found with neurodevelopment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Comparative Analysis and Distribution of Omega-3 lcPUFA Biosynthesis Genes in Marine Molluscs

PubMed Central

Surm, Joachim M.; Prentis, Peter J.; Pavasovic, Ana

2015-01-01

Recent research has identified marine molluscs as an excellent source of omega-3 long-chain polyunsaturated fatty acids (lcPUFAs), based on their potential for endogenous synthesis of lcPUFAs. In this study we generated a representative list of fatty acyl desaturase (Fad) and elongation of very long-chain fatty acid (Elovl) genes from major orders of Phylum Mollusca, through the interrogation of transcriptome and genome sequences, and various publicly available databases. We have identified novel and uncharacterised Fad and Elovl sequences in the following species: Anadara trapezia, Nerita albicilla, Nerita melanotragus, Crassostrea gigas, Lottia gigantea, Aplysia californica, Loligo pealeii and Chlamys farreri. Based on alignments of translated protein sequences of Fad and Elovl genes, the haeme binding motif and histidine boxes of Fad proteins, and the histidine box and seventeen important amino acids in Elovl proteins, were highly conserved. Phylogenetic analysis of aligned reference sequences was used to reconstruct the evolutionary relationships for Fad and Elovl genes separately. Multiple, well resolved clades for both the Fad and Elovl sequences were observed, suggesting that repeated rounds of gene duplication best explain the distribution of Fad and Elovl proteins across the major orders of molluscs. For Elovl sequences, one clade contained the functionally characterised Elovl5 proteins, while another clade contained proteins hypothesised to have Elovl4 function. Additional well resolved clades consisted only of uncharacterised Elovl sequences. One clade from the Fad phylogeny contained only uncharacterised proteins, while the other clade contained functionally characterised delta-5 desaturase proteins. The discovery of an uncharacterised Fad clade is particularly interesting as these divergent proteins may have novel functions. Overall, this paper presents a number of novel Fad and Elovl genes suggesting that many mollusc groups possess most of the
(n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary?

PubMed

Mozaffarian, Dariush; Wu, Jason H Y

2012-03-01

Considerable research supports cardiovascular benefits of consuming omega-3 PUFA, also known as (n-3) PUFA, from fish or fish oil. Whether individual long-chain (n-3) PUFA have shared or complementary effects is not well established. We reviewed evidence for dietary and endogenous sources and cardiovascular effects on biologic pathways, physiologic risk factors, and clinical endpoints of EPA [20:5(n-3)], docosapentaenoic acid [DPA, 22:5(n-3)], and DHA [22:6(n-3)]. DHA requires direct dietary consumption, with little synthesis from or retroconversion to DPA or EPA. Whereas EPA is also largely derived from direct consumption, EPA can also be synthesized in small amounts from plant (n-3) precursors, especially stearidonic acid. In contrast, DPA appears principally derived from endogenous elongation from EPA, and DPA can also undergo retroconversion back to EPA. In experimental and animal models, both EPA and DHA modulate several relevant biologic pathways, with evidence for some differential benefits. In humans, both fatty acids lower TG levels and, based on more limited studies, favorably affect cardiac diastolic filling, arterial compliance, and some metrics of inflammation and oxidative stress. All three (n-3) PUFA reduce ex vivo platelet aggregation and DHA also modestly increases LDL and HDL particle size; the clinical relevance of such findings is uncertain. Combined EPA+DHA or DPA+DHA levels are associated with lower risk of fatal cardiac events and DHA with lower risk of atrial fibrillation, suggesting direct or indirect benefits of DHA for cardiac arrhythmias (although not excluding similar benefits of EPA or DPA). Conversely, EPA and DPA, but not DHA, are associated with lower risk of nonfatal cardiovascular endpoints in some studies, and purified EPA reduced risk of nonfatal coronary syndromes in one large clinical trial. Overall, for many cardiovascular pathways and outcomes, identified studies of individual (n-3) PUFA were relatively limited, especially
Effect of dietary n - 3 polyunsaturated fatty acids on oxidant/antioxidant status in macrosomic offspring of diabetic rats.

PubMed

Guermouche, B; Soulimane-Mokhtari, N A; Bouanane, S; Merzouk, H; Merzouk, S; Narce, M

2014-01-01

The aim of this work was to determine the effect of dietary n - 3 PUFA on oxidant/antioxidant status, in vitro very low and low density lipoprotein (VLDL-LDL), and VLDL-LDL-fatty acid composition in macrosomic pups of diabetic mothers. We hypothesized that n - 3 PUFA would improve oxidative stress in macrosomia. Diabetes was induced in female Wistar rats fed with the ISIO diet (control) or with the EPAX diet (enriched in n - 3 PUFAs), by streptozotocin. The macrosomic pups were killed at birth (day 0) and at adulthood (day 90). Lipid parameters and VLDL-LDL-fatty acid composition were investigated. The oxidant/antioxidant status was determined by measuring plasma oxygen radical absorbance capacity (ORAC), hydroperoxides, carbonyl proteins, and VLDL-LDL oxidation. Macrosomic rats of ISIO fed diabetic mothers showed an increase in plasma and VLDL-LDL-triglycerides and VLDL-LDL-cholesterol levels and altered VLDL-LDL-fatty acid composition. Plasma ORAC was low with high hydroperoxide and carbonyl protein levels. The in vitro oxidizability of VLDL-LDL was enhanced in these macrosomic rats. The EPAX diet corrected lipid parameters and improved oxidant/antioxidant status but increased VLDL-LDL susceptibility to oxidation. Macrosomia is associated with lipid abnormalities and oxidative stress. n - 3 PUFA exerts favorable effects on lipid metabolism and on the oxidant/antioxidant status of macrosomic rats. However, there are no evident effects on VLDL-LDL oxidation.
PUFA diets alter the microRNA expression profiles in an inflammation rat model

PubMed Central

ZHENG, ZHENG; GE, YINLIN; ZHANG, JINYU; XUE, MEILAN; LI, QUAN; LIN, DONGLIANG; MA, WENHUI

2015-01-01

Omega-3 and -6 polyunsaturated fatty acids (PUFAs) can directly or indirectly regulate immune homeostasis via inflammatory pathways, and components of these pathways are crucial targets of microRNAs (miRNAs). However, no study has examined the changes in the miRNA transcriptome during PUFA-regulated inflammatory processes. Here, we established PUFA diet-induced autoimmune-prone (AP) and autoimmune-averse (AA) rat models, and studied their physical characteristics and immune status. Additionally, miRNA expression patterns in the rat models were compared using microarray assays and bioinformatic methods. A total of 54 miRNAs were differentially expressed in common between the AP and the AA rats, and the changes in rno-miR-19b-3p, -146b-5p and -183-5p expression were validated using stem-loop reverse transcription-quantitative polymerase chain reaction. To better understand the mechanisms underlying PUFA-regulated miRNA changes during inflammation, computational algorithms and biological databases were used to identify the target genes of the three validated miRNAs. Furthermore, Gene Ontology (GO) term annotation and KEGG pathway analyses of the miRNA targets further allowed to explore the potential implication of the miRNAs in inflammatory pathways. The predicted PUFA-regulated inflammatory pathways included the Toll-like receptor (TLR), T cell receptor (TCR), NOD-like receptor (NLR), RIG-I-like receptor (RLR), mitogen-activated protein kinase (MAPK) and the transforming growth factor-β (TGF-β) pathway. This study is the first report, to the best of our knowledge, on in vivo comparative profiling of miRNA transcriptomes in PUFA diet-induced inflammatory rat models using a microarray approach. The results provide a useful resource for future investigation of the role of PUFA-regulated miRNAs in immune homeostasis. PMID:25672643

Does consumption of LC omega-3 PUFA enhance cognitive performance in healthy school-aged children and throughout adulthood? Evidence from clinical trials.

PubMed

Stonehouse, Welma

2014-07-22

Long-chain (LC) omega-3 PUFA derived from marine sources may play an important role in cognitive performance throughout all life stages. Docosahexaenoic acid (DHA), the dominant omega-3 in the brain, is a major component of neuronal cell membranes and affects various neurological pathways and processess. Despite its critical role in brain function, human's capacity to synthesize DHA de novo is limited and its consumption through the diet is important. However, many individuals do not or rarely consume seafood. The aim of this review is to critically evaluate the current evidence from randomised controlled trials (RCT) in healthy school-aged children, younger and older adults to determine whether consumption of LC omega-3 PUFA improves cognitive performance and to make recommendations for future research. Current evidence suggests that consumption of LC omega-3 PUFA, particularly DHA, may enhance cognitive performance relating to learning, cognitive development, memory and speed of performing cognitive tasks. Those who habitually consume diets low in DHA, children with low literacy ability and malnourished and older adults with age-related cognitive decline and mild cognitive impairment seem to benefit most. However, study design limitations in many RCTs hamper firm conclusions. The measurement of a uniform biomarker, e.g., % DHA in red blood cells, is essential to establish baseline DHA-status, to determine targets for cognitive performance and to facilitate dosage recommendations. It is recommended that future studies be at least 16 weeks in duration, account for potential interaction effects of gender, age and apolipoprotein E genotype, include vegan/vegetarian populations, include measures of speed of cognitive performance and include brain imaging technologies as supportive information on working mechanisms of LC omega-3 PUFA.
Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools.

PubMed

Taha, Ameer Y; Cheon, Yewon; Faurot, Keturah F; Macintosh, Beth; Majchrzak-Hong, Sharon F; Mann, J Douglas; Hibbeln, Joseph R; Ringel, Amit; Ramsden, Christopher E

2014-05-01

Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA. Published by Elsevier Ltd.
Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools

PubMed Central

Taha, Ameer Y.; Cheon, Yewon; Faurot, Keturah F.; MacIntosh, Beth; Majchrzak-Hong, Sharon F.; Mann, J. Douglas; Hibbeln, Joseph R.; Ringel, Amit; Ramsden, Christopher E.

2014-01-01

Background Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. Objective To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, change unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Design Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to: (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Results Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Conclusion Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFA for 12 weeks further increases n-3 PUFA plasma concentrations, but also reduces AA. PMID:24675168
Dietary Omega-3 Polyunsaturated Fatty Acids Prevent Vascular Dysfunction and Attenuate Cytochrome P4501A1 Expression by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin.

PubMed

Wiest, Elani F; Walsh-Wilcox, Mary T; Rothe, Michael; Schunck, Wolf-Hagen; Walker, Mary K

2016-11-01

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) found in fish protect against cardiovascular morbidity and mortality; however, many individuals avoid fish consumption due to concerns about pollutants. We tested the hypothesis that n-3 PUFAs would prevent vascular dysfunction induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). C57Bl/6 male mice were fed a chow or n-3 PUFA diet for 10 weeks and were exposed to vehicle or 300 ng/kg/d TCDD during the final 2 weeks on each diet. Aortic vasoconstriction mediated by arachidonic acid (AA) ± SKF525 (P450 inhibitor) or SQ29548 (thromboxane/prostanoid [TP] receptor antagonist) was assessed. RBC fatty acids and expression of n-3 and n-6 PUFA metabolites were analyzed. Cytochrome P4501A1 (CYP1A1), CYP1B1, and aryl hydrocarbon receptor (AHR) expression was measured. TCDD significantly increased AA-mediated vasoconstriction on a chow diet by increasing the contribution of P450s and TP receptor to the constriction response. In contrast, the n-3 PUFA diet prevented the TCDD-induced increase in AA vasoconstriction and normalized the contribution of P450s and TP receptor. Although TCDD increased the levels of AA vasoconstrictors on the chow diet, this increase was prevent by the n-3 PUFA diet. Additionally, the n-3 PUFA diet significantly increased the levels of n-3 PUFA-derived vasodilators and TCDD increased these levels further. Interestingly, the n-3 PUFA diet significantly attenuated CYP1A1 induction by TCDD without a significant effect on AHR expression. These data suggest that n-3 PUFAs can prevent TCDD-induced vascular dysfunction by decreasing vasoconstrictors, increasing vasodilators, and attenuating CYP1A1 induction, which has been shown previously to contribute to TCDD-induced vascular dysfunction. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Omega-3 and omega-6 fatty acids suppress ER- and oxidative stress in cultured neurons and neuronal progenitor cells from mice lacking PPT1.

PubMed

Kim, Sung-Jo; Zhang, Zhongjian; Saha, Arjun; Sarkar, Chinmoy; Zhao, Zhenwen; Xu, Yan; Mukherjee, Anil B

2010-08-02

Reactive oxygen species (ROS) damage brain lipids, carbohydrates, proteins, as well as DNA and may contribute to neurodegeneration. We previously reported that ER- and oxidative stress cause neuronal apoptosis in infantile neuronal ceroid lipofuscinosis (INCL), a lethal neurodegenerative storage disease, caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. Polyunsaturated fatty acids (PUFA) are essential components of cell membrane phospholipids in the brain and excessive ROS may cause oxidative damage of PUFA leading to neuronal death. Using cultured neurons and neuroprogenitor cells from mice lacking Ppt1, which mimic INCL, we demonstrate that Ppt1-deficient neurons and neuroprogenitor cells contain high levels of ROS, which may cause peroxidation of PUFA and render them incapable of providing protection against oxidative stress. We tested whether treatment of these cells with omega-3 or omega-6 PUFA protects the neurons and neuroprogenitor cells from oxidative stress and suppress apoptosis. We report here that both omega-3 and omega-6 fatty acids protect the Ppt1-deficient cells from ER- as well as oxidative stress and suppress apoptosis. Our results suggest that PUFA supplementation may have neuroprotective effects in INCL. Published by Elsevier Ireland Ltd.
Impact of Lactobacillus fermentum and dairy lipids in the maternal diet on the fatty acid composition of pups' brain and peripheral tissues.

PubMed

Joffre, C; Dinel, A L; Aubert, A; Fressange-Mazda, C; Le Ruyet, P; Layé, S

2016-12-01

The aim of the study was to determine the effect of maternal diets administered since day 1 of gestation and containing dairy lipids or vegetable oils differing in the supply of n-3 polyunsaturated fatty acids (n-3 PUFAs) (equilibrated or deficient) and of Lactobacillus fermentum (L. fermentum) on the docosahexaenoic acid (DHA) accretion in the pups at postnatal day 14 in the prefrontal cortex (PFC) and hippocampus (HC) for brain structures and in the liver and adipose tissue for peripheral tissues. Maternal milk fatty acid composition was also assessed by analyzing the fatty acid composition of the gastric content of the pups. DHA was higher in mice supplemented with L. fermentum than in mice in the deficient group in HC and PFC and also in liver and adipose tissue. This increase could be linked to the slight but significant increase in C18:3n-3 in the maternal milk. This proportion was comparable in the dairy lipid group for which the brain DHA level was the highest. L. fermentum may have a key role in the protection of the brain during the perinatal period via the neuronal accretion of n-3 PUFAs, especially during n-3 PUFA deficiency. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Modification of high saturated fat diet with n-3 polyunsaturated fat improves glucose intolerance and vascular dysfunction

PubMed Central

Lamping, KL; Nuno, DW; Coppey, LJ; Holmes, AJ; Hu, S; Oltman, CL; Norris, AW; Yorek, MA

2013-01-01

Aims The ability of dietary enrichment with monounsaturated (MUFA), n-3, or n-6 polyunsaturated fatty acids (PUFA) to reverse glucose intolerance and vascular dysfunction resulting from excessive dietary saturated fatty acids is not resolved. We hypothesized that partial replacement of dietary saturated fats with n-3 PUFA enriched menhaden oil (MO) would provide greater improvement in glucose tolerance and vascular function compared to n-6 enriched safflower oil (SO) or MUFA-enriched olive oil (OO). Material and Methods We fed mice a high saturated fat diet (60% kcal from lard) for 12 weeks before substituting half the lard with MO, SO or OO for an additional 4 weeks. At the end of 4 weeks, we assessed glucose tolerance, insulin signaling and reactivity of isolated pressurized gracilis arteries. Results After 12 weeks of saturated fat diet, body weights were elevated and glucose tolerance abnormal compared to mice on control diet (13% kcal lard). Diet substituted with MO restored basal glucose levels, glucose tolerance, and indices of insulin signaling (phosphorylated Akt) to normal whereas restoration was limited for SO and OO substitutions. Although dilation to acetylcholine was reduced in arteries from mice on HF, OO and SO diets compared to normal diet, dilation to acetylcholine was fully restored and constriction to phenylephrine reduced in MO fed mice compared to normal. Conclusion We conclude that short term enrichment of an ongoing high fat diet with n-3 PUFA rich MO but not MUFA rich OO or n-6 PUFA rich SO reverses glucose tolerance, insulin signaling, and vascular dysfunction. PMID:22950668
The effects of omega-3 polyunsaturated Fatty Acid consumption on mammary carcinogenesis.

PubMed

Witte, Theodore R; Hardman, W Elaine

2015-05-01

The consumption of omega-3 polyunsaturated fatty acids (n-3 PUFA) is associated with a reduced risk of breast cancer. Studies in animals and in vitro have demonstrated mechanisms that could explain this apparent effect, but clinical and epidemiological studies have returned conflicting results on the practical benefits of dietary n-3 PUFA for prevention of breast cancer. Effects are often only significant within a population when comparing the highest n-3 PUFA consumption group to the lowest n-3 group or highest n-6 group. The beneficial effects of n-3 PUFA eicosapentaenoic and docosahexaenoic on the risk of breast cancer are dose dependent and are negatively affected by total n-6 consumption. The majority of the world population, including the most highly developed regions, consumes insufficient n-3 PUFA to significantly reduce breast cancer risk. This review discusses the physiological and dietary context in which reduction of breast cancer risk may occur, some proposed mechanisms of action and meaningful recommendations for consumption of n-3 PUFA in the diet of developed regions.
(n-3) Fatty Acids and Cardiovascular Health: Are Effects of EPA and DHA Shared or Complementary?123

PubMed Central

Mozaffarian, Dariush; Wu, Jason H. Y.

2012-01-01

Considerable research supports cardiovascular benefits of consuming omega-3 PUFA, also known as (n-3) PUFA, from fish or fish oil. Whether individual long-chain (n-3) PUFA have shared or complementary effects is not well established. We reviewed evidence for dietary and endogenous sources and cardiovascular effects on biologic pathways, physiologic risk factors, and clinical endpoints of EPA [20:5(n-3)], docosapentaenoic acid [DPA, 22:5(n-3)], and DHA [22:6(n-3)]. DHA requires direct dietary consumption, with little synthesis from or retroconversion to DPA or EPA. Whereas EPA is also largely derived from direct consumption, EPA can also be synthesized in small amounts from plant (n-3) precursors, especially stearidonic acid. In contrast, DPA appears principally derived from endogenous elongation from EPA, and DPA can also undergo retroconversion back to EPA. In experimental and animal models, both EPA and DHA modulate several relevant biologic pathways, with evidence for some differential benefits. In humans, both fatty acids lower TG levels and, based on more limited studies, favorably affect cardiac diastolic filling, arterial compliance, and some metrics of inflammation and oxidative stress. All three (n-3) PUFA reduce ex vivo platelet aggregation and DHA also modestly increases LDL and HDL particle size; the clinical relevance of such findings is uncertain. Combined EPA+DHA or DPA+DHA levels are associated with lower risk of fatal cardiac events and DHA with lower risk of atrial fibrillation, suggesting direct or indirect benefits of DHA for cardiac arrhythmias (although not excluding similar benefits of EPA or DPA). Conversely, EPA and DPA, but not DHA, are associated with lower risk of nonfatal cardiovascular endpoints in some studies, and purified EPA reduced risk of nonfatal coronary syndromes in one large clinical trial. Overall, for many cardiovascular pathways and outcomes, identified studies of individual (n-3) PUFA were relatively limited, especially
Biofortification of safflower: an oil seed crop engineered for ALA-targeting better sustainability and plant based omega-3 fatty acids.

PubMed

Rani, Arti; Panwar, Asha; Sathe, Manjary; Chandrashekhara, Karunakara Alageri; Kush, Anil

2018-05-11

Alpha-linolenic acid (ALA) deficiency and a skewed n6:n3 fatty acid ratio in the diet is a major explanation for the prevalence of cardiovascular diseases and inflammatory/autoimmune diseases. There is mounting evidence of the health benefits associated with omega-3 long chain polyunsaturated fatty acids (LC PUFA's). Although present in abundance in fish, a number of factors limit our consumption of fish based omega-3 PUFA's. To name a few, overexploitation of wild fish stocks has reduced their sustainability due to increased demand of aquaculture for fish oil and meal; the pollution of marine food webs has raised concerns over the ingestion of toxic substances such as heavy metals and dioxins; vegetarians do not consider fish-based sources for supplemental nutrition. Thus alternative sources are being sought and one approach to the sustainable supply of LC-PUFAs is the metabolic engineering of transgenic plants with the capacity to synthesize n3 LC-PUFAs. The present investigation was carried out with the goal of developing transgenic safflower capable of producing pharmaceutically important alpha-linolenic acid (ALA, C18:3, n3). This crop was selected as the seeds accumulate ~ 78% of the total fatty acids as linoleic acid (LA, C18:2, n6), the immediate precursor of ALA. In the present work, ALA production was achieved successfully in safflower seeds by transforming safflower hypocotyls with Arabidopsis specific delta 15 desaturase (FAD3) driven by truncated seed specific promoter. Transgenic safflower fortified with ALA is not only potentially valuable nutritional superior novel oil but also has reduced ratio of LA to ALA which is required for good health.
Perinatal ω-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood

PubMed Central

Jayasooriya, Anura P.; Ackland, M. Leigh; Mathai, Michael L.; Sinclair, Andrew J.; Weisinger, Harrison S.; Weisinger, Richard S.; Halver, John E.; Kitajka, Klára; Puskás, László G.

2005-01-01

Dietary ω-3 polyunsaturated fatty acid (PUFA) influences the expression of a number of genes in the brain. Zinc transporter (ZnT) 3 has been identified as a putative transporter of zinc into synaptic vesicles of neurons and is found in brain areas such as hippocampus and cortex. Neuronal zinc is involved in the formation of amyloid plaques, a major characteristic of Alzheimer's disease. The present study evaluated the influence of dietary ω-3 PUFA on the expression of the ZnT3 gene in the brains of adult male Sprague-Dawley rats. The rats were raised and/or maintained on a control (CON) diet that contained ω-3 PUFA or a diet deficient (DEF) in ω-3 PUFA. ZnT3 gene expression was analyzed by using real-time PCR, free zinc in brain tissue was determined by zinquin staining, and total zinc concentrations in plasma and cerebrospinal fluid were determined by atomic absorption spectrophotometry. Compared with CON-raised animals, DEF-raised animals had increased expression of ZnT3 in the brain that was associated with an increased level of free zinc in the hippocampus. In addition, compared with CON-raised animals, DEF-raised animals had decreased plasma zinc level. No difference in cerebrospinal fluid zinc level was observed. The results suggest that overexpression of ZnT3 due to a perinatal ω-3 PUFA deficiency caused abnormal zinc metabolism in the brain. Conceivably, the influence of dietary ω-3 PUFA on brain zinc metabolism could explain the observation made in population studies that the consumption of fish is associated with a reduced risk of dementia and Alzheimer's disease. PMID:15883362
Perinatal omega-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood.

PubMed

Jayasooriya, Anura P; Ackland, M Leigh; Mathai, Michael L; Sinclair, Andrew J; Weisinger, Harrison S; Weisinger, Richard S; Halver, John E; Kitajka, Klára; Puskás, László G

2005-05-17

Dietary omega-3 polyunsaturated fatty acid (PUFA) influences the expression of a number of genes in the brain. Zinc transporter (ZnT) 3 has been identified as a putative transporter of zinc into synaptic vesicles of neurons and is found in brain areas such as hippocampus and cortex. Neuronal zinc is involved in the formation of amyloid plaques, a major characteristic of Alzheimer's disease. The present study evaluated the influence of dietary omega-3 PUFA on the expression of the ZnT3 gene in the brains of adult male Sprague-Dawley rats. The rats were raised and/or maintained on a control (CON) diet that contained omega-3 PUFA or a diet deficient (DEF) in omega-3 PUFA. ZnT3 gene expression was analyzed by using real-time PCR, free zinc in brain tissue was determined by zinquin staining, and total zinc concentrations in plasma and cerebrospinal fluid were determined by atomic absorption spectrophotometry. Compared with CON-raised animals, DEF-raised animals had increased expression of ZnT3 in the brain that was associated with an increased level of free zinc in the hippocampus. In addition, compared with CON-raised animals, DEF-raised animals had decreased plasma zinc level. No difference in cerebrospinal fluid zinc level was observed. The results suggest that overexpression of ZnT3 due to a perinatal omega-3 PUFA deficiency caused abnormal zinc metabolism in the brain. Conceivably, the influence of dietary omega-3 PUFA on brain zinc metabolism could explain the observation made in population studies that the consumption of fish is associated with a reduced risk of dementia and Alzheimer's disease.
Does Consumption of LC Omega-3 PUFA Enhance Cognitive Performance in Healthy School-Aged Children and throughout Adulthood? Evidence from Clinical Trials

PubMed Central

Stonehouse, Welma

2014-01-01

Long-chain (LC) omega-3 PUFA derived from marine sources may play an important role in cognitive performance throughout all life stages. Docosahexaenoic acid (DHA), the dominant omega-3 in the brain, is a major component of neuronal cell membranes and affects various neurological pathways and processess. Despite its critical role in brain function, human’s capacity to synthesize DHA de novo is limited and its consumption through the diet is important. However, many individuals do not or rarely consume seafood. The aim of this review is to critically evaluate the current evidence from randomised controlled trials (RCT) in healthy school-aged children, younger and older adults to determine whether consumption of LC omega-3 PUFA improves cognitive performance and to make recommendations for future research. Current evidence suggests that consumption of LC omega-3 PUFA, particularly DHA, may enhance cognitive performance relating to learning, cognitive development, memory and speed of performing cognitive tasks. Those who habitually consume diets low in DHA, children with low literacy ability and malnourished and older adults with age-related cognitive decline and mild cognitive impairment seem to benefit most. However, study design limitations in many RCTs hamper firm conclusions. The measurement of a uniform biomarker, e.g., % DHA in red blood cells, is essential to establish baseline DHA-status, to determine targets for cognitive performance and to facilitate dosage recommendations. It is recommended that future studies be at least 16 weeks in duration, account for potential interaction effects of gender, age and apolipoprotein E genotype, include vegan/vegetarian populations, include measures of speed of cognitive performance and include brain imaging technologies as supportive information on working mechanisms of LC omega-3 PUFA. PMID:25054550
Association of serum n-3 polyunsaturated fatty acids with psychological distress in the second and third trimesters of pregnancy: Adjunct Study of Japan Environment and Children's Study.

PubMed

Hamazaki, Kei; Harauma, Akiko; Tanabe, Satoru; Namai, Miho; Moriguchi, Toru; Inadera, Hidekuni

2016-11-01

The results of several epidemiological studies and clinical trials investigating the effects of n-3 polyunsaturated fatty acids (PUFAs) on antenatal and postnatal depression remain controversial. In a previous case-control study of early pregnancy in Japan, we found an inverse association between eicosapentaenoic acid and risk of psychological distress after adjusting for possible confounders. Here, in a 1:2 matched case-control study, we further investigated the possible relationship between serum n-3 PUFAs and risk of psychological distress in the second and third trimesters of pregnancy. The psychological distress group (n=71) consisted of subjects with a score of ≥13 on the Kessler Psychological Distress Scale. The control group (n=142) was matched for age, educational level, and family income. Fatty acid composition of total lipid was determined from serum samples by gas chromatography. Associations between fatty acid levels and incidence of psychological distress were evaluated by logistic regression. Sixty-six percent of blood samples were collected in the second trimester and the remainder in the third. There were no significant differences in any of the n-3 PUFAs between the two groups. After adjustment for possible confounders, none of the n-3 PUFAs showed an association with risk of psychological distress. Peripheral n-3 PUFA levels might not influence the risk of psychological distress in later pregnancy. Further research is warranted to clarify this finding. Copyright © 2016 Elsevier Ltd. All rights reserved.
Effect of consumption of tomato juice enriched with n-3 polyunsaturated fatty acids on the lipid profile, antioxidant biomarker status, and cardiovascular disease risk in healthy women.

PubMed

García-Alonso, F J; Jorge-Vidal, V; Ros, G; Periago, M J

2012-06-01

We compared the effects of consumption of n-3 polyunsaturated fatty acids (PUFA)-enriched tomato juice versus plain tomato juice on the serum lipid profile and levels of biomarkers related to antioxidant status and cardiovascular disease (CVD) risk in women. Eighteen healthy women participated in a 2-week intervention trial involving the daily intake of 500 mL of n-3 PUFA-enriched juice (n = 11) or plain tomato juice (n = 7). Each serving of enriched juice provided 250 mg of eicosapentaenoic acid (EPA) plus docosahexanoic acid (DHA). Both juices provided natural antioxidant compounds such as phenolics (181 mg) and lycopene (26.5 mg). Intervention with the enriched juice had no effect on the lipid profile, and serum levels of triglycerides and cholesterol (total, LDL, and HDL) remained unchanged. The serum antioxidant status improved following juice intake, as revealed by an increase in total antioxidant capacity and a slight decrease in lipid peroxidation. The serum levels of homocysteine, a cardiovascular risk factor, decreased following n-3 PUFA-enriched juice consumption. A decrease in vascular adhesion molecule 1 (VCAM-1) levels was also noted after intake of either plain or enriched tomato juice, whereas intercellular adhesion molecule 1 (ICAM-1) levels only decreased following intake of the enriched juice. Overall, stronger positive amelioration of CVD risk factors was observed following the intake of n-3 PUFA-enriched juice than after plain tomato juice consumption, which suggested a possible synergistic action between n-3 PUFAs and tomato antioxidants.
Meta-analysis of erythrocyte polyunsaturated fatty acid biostatus in bipolar disorder.

PubMed

McNamara, Robert K; Welge, Jeffrey A

2016-05-01

Dietary deficiency in polyunsaturated fatty acids (PUFAs), including the omega-3 fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), and excesses in omega-6 fatty acids, including linoleic acid (LA; 18:2n-6) and arachidonic acid (AA; 20:4n-6), may be associated with the pathophysiology of bipolar disorder. In an effort to provide clarification regarding the relationship between PUFA biostatus and bipolar disorder, this meta-analysis investigated studies comparing erythrocyte (red blood cell) membrane PUFA composition in patients with bipolar disorder and healthy controls. A meta-analysis was performed on case-control studies comparing erythrocyte PUFA (EPA, DHA, LA and AA) levels in patients with bipolar I disorder and healthy controls. Standardized effect sizes were calculated and combined using a random effects model. Six eligible case-control studies comprising n = 118 bipolar I patients and n = 147 healthy controls were included in the analysis. Compared with healthy controls, patients with bipolar I disorder exhibited robust erythrocyte DHA deficits (p = 0.0008) and there was a trend for lower EPA (p = 0.086). There were no significant differences in LA (p = 0.42) or AA (p = 0.64). Bipolar I disorder is associated with robust erythrocyte DHA deficits. These findings add to a growing body of evidence implicating omega-3 PUFA deficiency in the pathophysiology of bipolar disorder. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
SCD1 activity in muscle increases triglyceride PUFA content, exercise capacity, and PPARδ expression in mice[S

PubMed Central

Rogowski, Michael P.; Flowers, Matthew T.; Stamatikos, Alexis D.; Ntambi, James M.; Paton, Chad M.

2013-01-01

Stearoyl-CoA desaturase (SCD)1 converts saturated fatty acids into monounsaturated fatty acids. Using muscle overexpression, we sought to determine the role of SCD1 expression in glucose and lipid metabolism and its effects on exercise capacity in mice. Wild-type C57Bl/6 (WT) and SCD1 muscle transgenic (SCD1-Tg) mice were generated, and expression of the SCD1 transgene was restricted to skeletal muscle. SCD1 overexpression was associated with increased triglyceride (TG) content. The fatty acid composition of the muscle revealed a significant increase in polyunsaturated fatty acid (PUFA) content of TG, including linoleate (18:2n6). Untrained SCD1-Tg mice also displayed significantly increased treadmill exercise capacity (WT = 6.6 ± 3 min, Tg = 71.9 ± 9.5 min; P = 0.0009). SCD1-Tg mice had decreased fasting plasma glucose, glucose transporter (GLUT)1 mRNA, fatty acid oxidation, mitochondrial content, and increased peroxisome proliferator-activated receptor (PPAR)δ and Pgc-1 protein expression in skeletal muscle. In vitro studies in C2C12 myocytes revealed that linoleate (18:2n6) and not oleate (18:1n9) caused a 3-fold increase in PPARδ and a 9-fold increase in CPT-1b with a subsequent increase in fat oxidation. The present model suggests that increasing delta-9 desaturase activity of muscle increases metabolic function, exercise capacity, and lipid oxidation likely through increased PUFA content, which increases PPARδ expression and activity. However, the mechanism of action that results in increased PUFA content of SCD1-Tg mice remains to be elucidated. PMID:23918045
Role of CYP1A1 in modulating the vascular and blood pressure benefits of omega-3 polyunsaturated fatty acids.

PubMed

Agbor, Larry N; Wiest, Elani F; Rothe, Michael; Schunck, Wolf-Hagen; Walker, Mary K

2014-12-01

The mechanisms that mediate the cardiovascular protective effects of omega 3 (n-3) polyunsaturated fatty acids (PUFAs) have not been fully elucidated. Cytochrome P450 1A1 efficiently metabolizes n-3 PUFAs to potent vasodilators. Thus, we hypothesized that dietary n-3 PUFAs increase nitric oxide (NO)-dependent blood pressure regulation and vasodilation in a CYP1A1-dependent manner. CYP1A1 wild-type (WT) and knockout (KO) mice were fed an n-3 or n-6 PUFA-enriched diet for 8 weeks and were analyzed for tissue fatty acids and metabolites, NO-dependent blood pressure regulation, NO-dependent vasodilation of acetylcholine (ACh) in mesenteric resistance arterioles, and endothelial NO synthase (eNOS) and phospho-Ser1177-eNOS expression in the aorta. All mice fed the n-3 PUFA diet showed significantly higher levels of n-3 PUFAs and their metabolites, and significantly lower levels of n-6 PUFAs and their metabolites. In addition, KO mice on the n-3 PUFA diet accumulated significantly higher levels of n-3 PUFAs in the aorta and kidney without a parallel increase in the levels of their metabolites. Moreover, KO mice exhibited significantly less NO-dependent regulation of blood pressure on the n-3 PUFA diet and significantly less NO-dependent, ACh-mediated vasodilation in mesenteric arterioles on both diets. Finally, the n-3 PUFA diet significantly increased aortic phospho-Ser1177-eNOS/eNOS ratio in the WT compared with KO mice. These data demonstrate that CYP1A1 contributes to eNOS activation, NO bioavailability, and NO-dependent blood pressure regulation mediated by dietary n-3 PUFAs. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.
Omega 3 and omega 6 fatty acids intake and dietary sources in a representative sample of Spanish adults.

PubMed

González-Rodríguez, Liliana G; Aparicio, Aránzazu; López-Sobaler, Ana M; Ortega, Rosa M

2013-01-01

The present study analyzes the intake of omega 3 (n-3 PUFAs) and omega 6 (n-6 PUFAs) and dietary sources in a representative sample of Spanish adults. For this purpose 418 adults (18 - 60 y), from 15 Spanish provinces were studied. The intake of energy and nutrients [specifically, the n-3 polyunsaturated fatty acids (PUFAs,) α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA); and the n-6 PUFA, linoleic acid (LA)] was determined using a 24-hour recall questionnaire for two days. The Multiple Source Method (MSM) was used to estimate participants usual fatty acid intake. The total n-3 PUFAs intake was 1.8 ± 0.60 g/day (ALA: 1.3 ± 0.32, EPA: 0.16 ± 0.14, and DHA: 0.33 ± 0.21 g/day) and n-6 PUFA intake was 11.0 ± 2.7 g/day (LA: 10.8 ± 2.7 g/day). A high proportion of participants did not meet their nutrient intake goals for total n-3 PUFAs (84.7 %), ALA (45.0 %), and EPA plus DHA (62.9 %). The main food sources for ALA were oil, dairy products, and meat; for EPA fish; for DHA, fish, eggs, and meat; and for LA, oils, meat, and cereals. Therefore, an increase in the intake of foods rich in n-3 PUFAs or the use of supplements with n-3 PUFAs might help to improve the n-3 PUFA intake.
Dietary omega-3 polyunsaturated fatty acids improve the neurolipidome and restore the DHA status while promoting functional recovery after experimental spinal cord injury.

PubMed

Figueroa, Johnny D; Cordero, Kathia; Llán, Miguel S; De Leon, Marino

2013-05-15

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome.

Dietary Omega-3 Polyunsaturated Fatty Acids Improve the Neurolipidome and Restore the DHA Status while Promoting Functional Recovery after Experimental Spinal Cord Injury

PubMed Central

Figueroa, Johnny D.; Cordero, Kathia; llán, Miguel S.

2013-01-01

Abstract Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome. PMID:23294084
Diversity of fatty acid composition of symbiotic dinoflagellates in corals: evidence for the transfer of host PUFAs to the symbionts.

PubMed

Imbs, Andrey B; Yakovleva, Irina M; Dautova, Tatiana N; Bui, Long H; Jones, Paul

2014-05-01

High diversity of fatty acid (FA) composition of endosymbiotic dinoflagellates of the Symbiodinium group (zooxanthellae) isolated from different cnidarian groups has been found. To explain this diversity, FA composition of the total lipids of pure symbiont fractions (SF) and host cell tissue fractions (HF) isolated from one hydrocoral, two soft coral, and seven hard coral species inhabiting the shallow waters of the South China Sea (Vietnam) were compared. Symbiodinium phylogenetic clade designation for each SF was also determined, however, the relationship between the clade designation and FA composition of Symbiodinium was not found. The profiles of marker polyunsaturated FAs (PUFAs) of symbionts (18:4n-3, 18:5n-3, 20:5n-3) did not depend on taxonomic designation of the host and reflected only a specimen-specific diversity of the SF lipids. Several FAs such as 20:0, C24 PUFAs, 22:5n-6, and 18:2n-7 concentrated in HF lipids but were also found in SF lipids. For ten cnidarian species studied, the principal components analysis of total FAs (27 variables) of the symbiotic fractions was performed. The clear division of the symbiotic dinoflagellates according to the host systematic identity was found on a subclass level. This division was mainly caused by the FAs specific for the host lipids of each cnidarian subclasses such as hard corals, soft corals, and hydrocorals. Thus, the coral hosts affect the FA profile of their symbionts and cause the diversity of FA composition of Symbiodinium. The transfer of FAs from the coral host to their symbiotic dinoflagellates and modulation of PUFA biosynthesis in symbionts by the host are considered as possible reasons of the diversity studied. Copyright © 2014 Elsevier Ltd. All rights reserved.
Genome-Wide Interaction Study of Omega-3 PUFAs and Other Fatty Acids on Inflammatory Biomarkers of Cardiovascular Health in the Framingham Heart Study.

PubMed

Veenstra, Jenna; Kalsbeek, Anya; Westra, Jason; Disselkoen, Craig; Smith, Caren; Tintle, Nathan

2017-08-18

Numerous genetic loci have been identified as being associated with circulating fatty acid (FA) levels and/or inflammatory biomarkers of cardiovascular health (e.g., C-reactive protein). Recently, using red blood cell (RBC) FA data from the Framingham Offspring Study, we conducted a genome-wide association study of over 2.5 million single nucleotide polymorphisms (SNPs) and 22 RBC FAs (and associated ratios), including the four Omega-3 FAs (ALA, DHA, DPA, and EPA). Our analyses identified numerous causal loci. In this manuscript, we investigate the extent to which polyunsaturated fatty acid (PUFA) levels moderate the relationship of genetics to cardiovascular health biomarkers using a genome-wide interaction study approach. In particular, we test for possible gene-FA interactions on 9 inflammatory biomarkers, with 2.5 million SNPs and 12 FAs, including all Omega-3 PUFAs. We identified eighteen novel loci, including loci which demonstrate strong evidence of modifying the impact of heritable genetics on biomarker levels, and subsequently cardiovascular health. The identified genes provide increased clarity on the biological functioning and role of Omega-3 PUFAs, as well as other common fatty acids, in cardiovascular health, and suggest numerous candidate loci for future replication and biological characterization.
Omega-3 fatty acid deficiency disrupts endocytosis, neuritogenesis, and mitochondrial protein pathways in the mouse hippocampus

PubMed Central

English, Jane A.; Harauma, Akiko; Föcking, Melanie; Wynne, Kieran; Scaife, Caitriona; Cagney, Gerard; Moriguchi, Toru; Cotter, David R.

2013-01-01

Omega-3 fatty acid (n-3 FA) deficiency is an environmental risk factor for schizophrenia, yet characterization of the consequences of deficiency at the protein level in the brain is limited. We aimed to identify the protein pathways disrupted as a consequence of chronic n-3 deficiency in the hippocampus of mice. Fatty acid analysis of the hippocampus following chronic dietary deficiency revealed a 3-fold decrease (p < 0.001) in n-3 FA levels. Label free LC-MS/MS analysis identified and profiled 1008 proteins, of which 114 were observed to be differentially expressed between n-3 deficient and control groups (n = 8 per group). The cellular processes that were most implicated were neuritogenesis, endocytosis, and exocytosis, while specific protein pathways that were most significantly dysregulated were mitochondrial dysfunction and clathrin mediated endocytosis (CME). In order to characterize whether these processes and pathways are ones influenced by antipsychotic medication, we used LC-MS/MS to test the differential expression of these 114 proteins in the hippocampus of mice chronically treated with the antipsychotic agent haloperidol. We observed 23 of the 114 proteins to be differentially expressed, 17 of which were altered in the opposite direction to that observed following n-3 deficiency. Overall, our findings point to disturbed synaptic function, neuritogenesis, and mitochondrial function as a consequence of dietary deficiency in n-3 FA. This study greatly aids our understanding of the molecular mechanism by which n-3 deficiency impairs normal brain function, and provides clues as to how n-3 FA exert their therapeutic effect in early psychosis. PMID:24194745
Deficiency of Lipoprotein Lipase in Neurons Decreases AMPA Receptor Phosphorylation and Leads to Neurobehavioral Abnormalities in Mice

PubMed Central

Yu, Tian; Taussig, Matthew D.; DiPatrizio, Nicholas V.; Astarita, Giuseppe; Piomelli, Daniele; Bergman, Bryan C.; Dell’Acqua, Mark L.; Eckel, Robert H.; Wang, Hong

2015-01-01

Alterations in lipid metabolism have been found in several neurodegenerative disorders, including Alzheimer’s disease. Lipoprotein lipase (LPL) hydrolyzes triacylglycerides in lipoproteins and regulates lipid metabolism in multiple organs and tissues, including the central nervous system (CNS). Though many brain regions express LPL, the functions of this lipase in the CNS remain largely unknown. We developed mice with neuron-specific LPL deficiency that became obese on chow by 16 wks in homozygous mutant mice (NEXLPL-/-) and 10 mo in heterozygous mice (NEXLPL+/-). In the present study, we show that 21 mo NEXLPL+/- mice display substantial cognitive function decline including poorer learning and memory, and increased anxiety with no difference in general motor activities and exploratory behavior. These neurobehavioral abnormalities are associated with a reduction in the 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) receptor subunit GluA1 and its phosphorylation, without any alterations in amyloid β accumulation. Importantly, a marked deficit in omega-3 and omega-6 polyunsaturated fatty acids (PUFA) in the hippocampus precedes the development of the neurobehavioral phenotype of NEXLPL+/- mice. And, a diet supplemented with n-3 PUFA can improve the learning and memory of NEXLPL+/- mice at both 10 mo and 21 mo of age. We interpret these findings to indicate that LPL regulates the availability of PUFA in the CNS and, this in turn, impacts the strength of synaptic plasticity in the brain of aging mice through the modification of AMPA receptor and its phosphorylation. PMID:26263173
Long-chain n-3 fatty acids enhance neonatal insulin-regulated protein metabolism in piglets by differentially altering muscle lipid composition

PubMed Central

Bergeron, Karen; Julien, Pierre; Davis, Teresa A.; Myre, Alexandre; Thivierge, M. Carole

2009-01-01

This study investigated the role of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFAs) of muscle phospholipids in the regulation of neonatal metabolism. Twenty-eight piglets were weaned at 2 days of age and raised on one of two milk formulas that consisted of either a control formula supplying 0% or a formula containing 3.5% LCn-3PUFAs until 10 or 28 days of age. There was a developmental decline in the insulin sensitivity of amino acid disposal in control pigs during the first month of life, with a slope of −2.24 μmol·kg−1·h−1 (P = 0.01) per unit of insulin increment, as assessed using hyperinsulinemic-euglycemic-euaminoacidemic clamps. LCn-3PUFA feeding blunted this developmental decline, resulting in differing insulin sensitivities (P < 0.001). When protein metabolism was assessed under parenteral feeding-induced hyperinsulinemia, LCn-3PUFAs reduced by 16% whole body oxidative losses of amino acids (from 238 to 231 μmol·kg−1·h−1; P = 0.06), allowing 41% more amino acids to accrete into body proteins (from 90 to 127 μmol·kg−1·h−1; P = 0.06). The fractional synthetic rate of muscle mixed proteins remained unaltered by the LCn-3PUFA feeding. However, LCn-3PUFAs retarded a developmental increase in the essential-to-nonessential amino acid ratio of the muscle intracellular free pool (P = 0.05). Overall, alterations in metabolism were concomitant with a preferential incorporation of LCn-3PUFAs into muscle total membrane phospholipids (P < 0.001), in contrast to intramuscular triglycerides. These results underscore the potential role of LCn-3PUFAs as regulators of different aspects of protein metabolism in the neonate. PMID:17673528
Blockade by N-3 polyunsaturated fatty acid of the Kv4.3 current stably expressed in Chinese hamster ovary cells

PubMed Central

Singleton, C B; Valenzuela, S M; Walker, B D; Tie, H; Wyse, K R; Bursill, J A; Qiu, M R; Breit, S N; Campbell, T J

1999-01-01

The Kv4.3 gene is believed to encode a large proportion of the transient outward current (Ito), responsible for the early phase of repolarization of the human cardiac action potential. There is evidence that this current is involved in the dispersion of refractoriness which develops during myocardial ischaemia and which predisposes to the development of potentially fatal ventricular tachyarrhythmias. Epidemiological, clinical, animal, and cellular studies indicate that these arrhythmias may be ameliorated in myocardial ischaemia by n-3 polyunsaturated fatty acids (n-3 PUFA) present in fish oils. We describe stable transfection of the Kv4.3 gene into a mammalian cell line (Chinese hamster ovary cells), and using patch clamp techniques have shown that the resulting current closely resembles human Ito. The current is rapidly activating and inactivating, with both processes being well fit by double exponential functions (time constants of 3.8±0.2 and 5.3±0.4 ms for activation and 20.0±1.2 and 96.6±6.7 ms for inactivation at +45 mV at 23°C). Activation and steady state inactivation both show voltage dependence (V1/2 of activation=−6.7±2.5 mV, V1/2 of steady state inactivation=−51.3±0.2 mV at 23°C). Current inactivation and recovery from inactivation are faster at physiologic temperature (37°C) compared to room temperature (23°C). The n-3 PUFA docosahexaenoic acid blocks the Kv4.3 current with an IC50 of 3.6 μmol L−1. Blockade of the transient outward current may be an important mechanism by which n-3 PUFA provide protection against the development of ventricular fibrillation during myocardial ischaemia. PMID:10433502
Omega-3 fatty acids (fish-oil) and depression-related cognition in healthy volunteers.

PubMed

Antypa, N; Van der Does, A J W; Smelt, A H M; Rogers, R D

2009-09-01

Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation may be beneficial in the treatment of several psychiatric disorders, including depression. A small number of studies have suggested that there may also be cognitive and mood effects in healthy samples. The purpose of the present study was to investigate the effects of n-3 PUFA on depression-relevant cognitive functioning in healthy individuals. Fifty-four healthy university students were randomized to receive either n-3 PUFA supplements or placebo for 4 weeks in a double-blind design. The test battery included measures of cognitive reactivity, attention, response inhibition, facial emotion recognition, memory and risky decision-making. Results showed few effects of n-3 PUFAs on cognition and mood states. The n-3 PUFA group made fewer risk-averse decisions than the placebo group. This difference appeared only in non-normative trials of the decision-making test, and was not accompanied by increased impulsiveness. N-3 PUFAs improved scores on the control/perfectionism scale of the cognitive reactivity measure. No effects were found on the other cognitive tasks and no consistent effects on mood were observed. The present findings indicate that n-3 PUFA supplementation may have a selective effect on risky decision making in healthy volunteers, which is unrelated to impulsiveness.
n-3 and n-6 Fatty Acid Changes in the Erythrocyte Membranes of Patients with 658240251 Clostridium difficile Infection.

PubMed

Czepiel, Jacek; Gdula-Argasińska, Joanna; Garlicki, Aleksander

2016-01-01

The implications of circulating essential fatty acids (FA) on the inflammatory risk profile and clinical outcome are still unclear. In order to gain a deeper understanding of the role of polyunsaturated fatty acids (PUFA) in the pathogenesis of acute infection, we analyzed the FA content in red blood cell (RBC) membranes of patients with Clostridium difficile infection (CDI) and controls. We prospectively studied 60 patients including 30 patients with CDI and 30 controls to assess lipid concentrations in erythrocyte membranes using gas chromatography. We observed a higher level of saturated fatty acids (SFA) in RBC membranes from patients with CDI. In patients with CDI, we also noticed a higher level of 20:4 n-6 FA and only a small amounts of C20:2n-6, C20:3n-6 FAs, arachidonic acid (AA) precursors, which suggest an intense inflammatory reaction in the organism during infection. We also noticed low levels of n-3 FA in the RBC membranes of patients infected with CDI. There is a deficit of n-3 FA in patients with CDI. n-3 FA are probably used during CDI as precursors of pro-resolving mediators that may indicate a therapeutic role of n-3 PUFAs in CDI. The changes in fatty acids in erythrocyte membranes during CDI alter their functions which may have an impact on the clinical outcome.
Metabolic engineering of Pseudomonas putida for production of docosahexaenoic acid based on a myxobacterial PUFA synthase.

PubMed

Gemperlein, Katja; Zipf, Gregor; Bernauer, Hubert S; Müller, Rolf; Wenzel, Silke C

2016-01-01

Long-chain polyunsaturated fatty acids (LC-PUFAs) can be produced de novo via polyketide synthase-like enzymes known as PUFA synthases, which are encoded by pfa biosynthetic gene clusters originally discovered from marine microorganisms. Recently similar gene clusters were detected and characterized in terrestrial myxobacteria revealing several striking differences. As the identified myxobacterial producers are difficult to handle genetically and grow very slowly we aimed to establish heterologous expression platforms for myxobacterial PUFA synthases. Here we report the heterologous expression of the pfa gene cluster from Aetherobacter fasciculatus (SBSr002) in the phylogenetically distant model host bacteria Escherichia coli and Pseudomonas putida. The latter host turned out to be the more promising PUFA producer revealing higher production rates of n-6 docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). After several rounds of genetic engineering of expression plasmids combined with metabolic engineering of P. putida, DHA production yields were eventually increased more than threefold. Additionally, we applied synthetic biology approaches to redesign and construct artificial versions of the A. fasciculatus pfa gene cluster, which to the best of our knowledge represents the first example of a polyketide-like biosynthetic gene cluster modulated and synthesized for P. putida. Combination with the engineering efforts described above led to a further increase in LC-PUFA production yields. The established production platform based on synthetic DNA now sets the stage for flexible engineering of the complex PUFA synthase. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.
Whole Blood ω-3 Fatty Acids Are Inversely Associated with Carotid Intima-Media Thickness in Indigenous Mexican Women.

PubMed

Monge, Adriana; Harris, William S; Ortiz-Panozo, Eduardo; Yunes, Elsa; Cantu-Brito, Carlos; Catzin-Kuhlmann, Andres; López-Ridaura, Ruy; Lajous, Martín

2016-07-01

Long-chain ω-3 (n-3) polyunsaturated fatty acids (PUFAs) may reduce the risk of atherosclerosis. The association between n-3 PUFAs and cardiovascular disease may vary across different populations, and there is limited information on Hispanic individuals with mixed Amerindian and European origin. We evaluated the cross-sectional relations between whole blood n-3 PUFAs and carotid intima-media thickness (IMT) in Mexican women living in Mexico and assessed whether this relation was different in women who spoke an indigenous language compared with women who did not. In 2012-2013, we assessed the association between blood n-3 PUFAs and IMT in 1306 women free of disease in Chiapas and Yucatan, Mexico. We categorized blood n-3 PUFAs (% of total FAs) in quartiles and adjusted linear regression models by age, indigenous language, site, socioeconomic status, education, smoking, menopause, diabetes, hypertension, hypercholesterolemia, body mass index, physical activity, and diet. We stratified analyses by indigenous/nonindigenous language speakers (n = 315 of 991). Whole blood n-3 PUFAs (means ± SDs) were 3.58% ± 0.78% of total FAs. We did not observe a significant association between n-3 PUFAs and IMT in the overall study population. However, the adjusted mean difference of IMT was -6.5% (95% CI: -10.7%, -2.3%; P-trend < 0.0001) for indigenous women in the highest quartile compared with the lowest quartile of blood n-3 PUFAs. In nonindigenous women, we did not observe an association (-0.6%; 95% CI: -3.0%, 1.8%, comparing extreme quartiles; P-trend = 1.00). Overall, circulating n-3 PUFAs were not associated with IMT. However, we observed a strong statistically significant inverse association with IMT in indigenous Mexican women. Future studies should evaluate genetic markers that may reflect differences in n-3 PUFA metabolism across populations. © 2016 American Society for Nutrition.
High-protein-PUFA supplementation, red blood cell membranes, and plasma antioxidant activity in volleyball athletes.

PubMed

Malaguti, Marco; Baldini, Marta; Angeloni, Cristina; Biagi, Pierluigi; Hrelia, Silvana

2008-06-01

The authors evaluated the role of a high-protein, low-calorie, polyunsaturated fatty-acid (PUFA) -supplemented diet on anthropometric parameters, erythrocyte-membrane fatty-acid composition, and plasma antioxidant defenses of nonprofessional volleyball athletes. The athletes were divided in two groups: One (n = 5) followed the Mediterranean diet, and the other (n = 6) followed a high-protein, low-calorie diet with a 3-g/day fish-oil supplementation. All the athletes had anthropometric measurements taken, both at the beginning and at the end of the study, which lasted for 2 months. Body-mass index and total body fat were significantly diminished in the second group, while they remained unchanged in the first. Plasma total antioxidant activity (TAA) was significantly increased in the plasma of both groups, with no differences between the groups, suggesting that physical activity, not the different diets, is the main contributor to the increase of plasma TAA. The second group showed a significant increase in erythrocyte-membrane PUFA content and in the unsaturation index value (UI) because of the fish-oil supplementation.A high-protein, low-carbohydrate, fish-oil-supplemented diet seems to be useful only when the aim of the diet is to obtain weight loss in a short-term period. The significant increase in the UI of erythrocyte membranes indicates the potential for harm, because a high intake of PUFA might increase susceptibility to lipid peroxidation not counterbalanced by a higher increase in TAA. Adherence to the Mediterranean diet seems to be the better choice.
Fish Oil-Derived Long-Chain n-3 Polyunsaturated Fatty Acids Reduce Expression of M1-Associated Macrophage Markers in an ex vivo Adipose Tissue Culture Model, in Part through Adiponectin.

PubMed

De Boer, Anna A; Monk, Jennifer M; Liddle, Danyelle M; Power, Krista A; Ma, David W L; Robinson, Lindsay E

2015-01-01

Adipose tissue (AT) macrophages (ATM) play a key role in obesity-associated pathologies, and their phenotype can be influenced by the local tissue microenvironment. Interestingly, long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) and the LC n-3 PUFA-upregulated adipokine, adiponectin (Ad), may mitigate excessive ATM inflammatory M1-polarization responses. However, to what extent LC n-3 PUFA and Ad work in concert to affect macrophage phenotype has not been examined. Thus, we used an established ex vivo AT organ culture model using visceral AT from mice fed a control (CON; 10% w/w safflower oil) n-6 PUFA-rich diet or an isocaloric fish oil (FO; 3% w/w menhaden oil + 7% w/w safflower oil)-derived LC n-3 PUFA-rich diet to generate AT conditioned media (ACM). We then evaluated if CON or FO ACM affected macrophage polarization markers in a model designed to mimic acute [18 h ACM plus lipopolysaccharide (LPS) for the last 6 h] or chronic (macrophages treated with LPS-challenged CON or FO ACM for 24 h) inflammation ± Ad-neutralizing antibody and the LPS-neutralizing agent, polymyxin B. In the acute inflammation model, macrophages treated with FO ACM had decreased lipid uptake and mRNA expression of M1 markers (Nos2, Nfκb, Il6, Il18, Ccl2, and Ccl5) compared with CON ACM (p ≤ 0.05); however, these effects were largely attenuated when Ad was neutralized (p > 0.05). Furthermore, in the chronic inflammation model, macrophages treated with FO ACM had decreased mRNA expression of M1 markers (Nos2, Tnfα, Ccl2, and Il1β) and IL-6 and CCL2 secretion (p ≤ 0.05); however, some of these effects were lost when Ad was neutralized, and were further exacerbated when both Ad and LPS were neutralized. Taken together, this work shows that LC n-3 PUFA and Ad work in concert to suppress certain M1 macrophage responses. Thus, future strategies to modulate the ATM phenotype should consider the role of both LC n-3 PUFA and Ad in mitigating obese AT
Fish Oil-Derived Long-Chain n-3 Polyunsaturated Fatty Acids Reduce Expression of M1-Associated Macrophage Markers in an ex vivo Adipose Tissue Culture Model, in Part through Adiponectin

PubMed Central

De Boer, Anna A.; Monk, Jennifer M.; Liddle, Danyelle M.; Power, Krista A.; Ma, David W. L.; Robinson, Lindsay E.

2015-01-01

Adipose tissue (AT) macrophages (ATM) play a key role in obesity-associated pathologies, and their phenotype can be influenced by the local tissue microenvironment. Interestingly, long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) and the LC n-3 PUFA-upregulated adipokine, adiponectin (Ad), may mitigate excessive ATM inflammatory M1-polarization responses. However, to what extent LC n-3 PUFA and Ad work in concert to affect macrophage phenotype has not been examined. Thus, we used an established ex vivo AT organ culture model using visceral AT from mice fed a control (CON; 10% w/w safflower oil) n-6 PUFA-rich diet or an isocaloric fish oil (FO; 3% w/w menhaden oil + 7% w/w safflower oil)-derived LC n-3 PUFA-rich diet to generate AT conditioned media (ACM). We then evaluated if CON or FO ACM affected macrophage polarization markers in a model designed to mimic acute [18 h ACM plus lipopolysaccharide (LPS) for the last 6 h] or chronic (macrophages treated with LPS-challenged CON or FO ACM for 24 h) inflammation ± Ad-neutralizing antibody and the LPS-neutralizing agent, polymyxin B. In the acute inflammation model, macrophages treated with FO ACM had decreased lipid uptake and mRNA expression of M1 markers (Nos2, Nfκb, Il6, Il18, Ccl2, and Ccl5) compared with CON ACM (p ≤ 0.05); however, these effects were largely attenuated when Ad was neutralized (p > 0.05). Furthermore, in the chronic inflammation model, macrophages treated with FO ACM had decreased mRNA expression of M1 markers (Nos2, Tnfα, Ccl2, and Il1β) and IL-6 and CCL2 secretion (p ≤ 0.05); however, some of these effects were lost when Ad was neutralized, and were further exacerbated when both Ad and LPS were neutralized. Taken together, this work shows that LC n-3 PUFA and Ad work in concert to suppress certain M1 macrophage responses. Thus, future strategies to modulate the ATM phenotype should consider the role of both LC n-3 PUFA and Ad in mitigating obese AT
Perinatal n-3 fatty acid deficiency selectively reduces myo-inositol levels in the adult rat PFC: an in vivo (1)H-MRS study.

PubMed

McNamara, Robert K; Able, Jessica; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lindquist, Diana M

2009-03-01

To investigate the effects of omega-3 fatty acid deficiency on phosphatidylinositol signaling in brain, myo-inositol (mI) concentrations were determined in the prefrontal cortex (PFC) of omega-3 fatty acid deficient rats by in vivo proton magnetic resonance spectroscopy ((1)H-MRS). To generate graded deficits in PFC docosahexaenoic acid (22:6n-3) (DHA) composition, perinatal and postweaning alpha-linolenic acid (18:3n-3) (ALA) deficiency models were used. Adult male rats were scanned in a 7T Bruker Biospec system and a (1)H-MRS spectrum acquired from the bilateral medial PFC. Rats were then challenged with SKF83959, a selective agonist at phosphoinositide (PI)-coupled dopamine D(1) receptors. Postmortem PFC fatty acid composition was determined by gas chromatography. Relative to controls, PFC DHA composition was significantly reduced in adult postweaning (-27%) and perinatal (-65%) ALA-deficiency groups. Basal PFC mI concentrations were significantly reduced in the perinatal deficiency group (-21%, P = 0.001), but not in the postweaning deficiency group (-1%, P = 0.86). Among all rats, DHA composition was positively correlated with mI concentrations and the mI/creatine (Cr) ratio. SKF83959 challenge significantly increased mI concentrations only in the perinatal deficiency group (+16%, P = 0.02). These data demonstrate that perinatal deficits in cortical DHA accrual significantly and selectively reduce mI concentrations and augment receptor-generated mI synthesis.
n-3 Fatty Acids Induce Neurogenesis of Predominantly POMC-Expressing Cells in the Hypothalamus.

PubMed

Nascimento, Lucas F R; Souza, Gabriela F P; Morari, Joseane; Barbosa, Guilherme O; Solon, Carina; Moura, Rodrigo F; Victório, Sheila C; Ignácio-Souza, Letícia M; Razolli, Daniela S; Carvalho, Hernandes F; Velloso, Lício A

2016-03-01

Apoptosis of hypothalamic neurons is believed to play an important role in the development and perpetuation of obesity. Similar to the hippocampus, the hypothalamus presents constitutive and stimulated neurogenesis, suggesting that obesity-associated hypothalamic dysfunction can be repaired. Here, we explored the hypothesis that n-3 polyunsaturated fatty acids (PUFAs) induce hypothalamic neurogenesis. Both in the diet and injected directly into the hypothalamus, PUFAs were capable of increasing hypothalamic neurogenesis to levels similar or superior to the effect of brain-derived neurotrophic factor (BDNF). Most of the neurogenic activity induced by PUFAs resulted in increased numbers of proopiomelanocortin but not NPY neurons and was accompanied by increased expression of BDNF and G-protein-coupled receptor 40 (GPR40). The inhibition of GPR40 was capable of reducing the neurogenic effect of a PUFA, while the inhibition of BDNF resulted in the reduction of global hypothalamic cell. Thus, PUFAs emerge as a potential dietary approach to correct obesity-associated hypothalamic neuronal loss. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Omega-3 Fatty Acids, Oxidative Stress, and Leukocyte Telomere Length: A Randomized Controlled Trial

PubMed Central

Kiecolt-Glaser, Janice K.; Epel, Elissa S.; Belury, Martha A.; Andridge, Rebecca; Lin, Jue; Glaser, Ronald; Malarkey, William B.; Hwang, Beom Seuk; Blackburn, Elizabeth

2012-01-01

Shorter telomeres have been associated with poor health behaviors, age-related diseases, and early mortality. Telomere length is regulated by the enzyme telomerase, and is linked to exposure to proinflammatory cytokines and oxidative stress. In our recent randomized controlled trial, omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation lowered the concentration of serum proinflammatory cytokines. This study assessed whether n-3 PUFA supplementation also affected leukocyte telomere length, telomerase, and oxidative stress. In addition to testing for group differences, changes in the continuous n-6:n-3 PUFA ratio were assessed to account for individual differences in adherence, absorption, and metabolism. The double-blind 4-month trial included 106 healthy sedentary overweight middle-aged and older adults who received (1) 2.5 g/day n-3 PUFAs, (2) l.25 g/day n-3 PUFAs, or (3) placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Supplementation significantly lowered oxidative stress as measured by F2-isoprostanes (p=0.02). The estimated geometric mean log-F2-isoprostanes values were 15% lower in the two supplemented groups compared to placebo. Although group differences for telomerase and telomere length were nonsignificant, changes in the n-6:n-3 PUFA plasma ratios helped clarify the intervention’s impact: telomere length increased with decreasing n-6:n-3 ratios, p=0.02. The data suggest that lower n-6:n-3 PUFA ratios can impact cell aging. The triad of inflammation, oxidative stress, and immune cell aging represents important pre-disease mechanisms that may be ameliorated through nutritional interventions. This translational research broadens our understanding of the potential impact of the n-6:n-3 PUFA balance. ClinicalTrials.gov identifier: NCT00385723 PMID:23010452
Food products as vehicles for n-3 fatty acid supplementation.

PubMed

Martin, Lisa; Zarn, Dayna; Hansen, Anne Marie; Wismer, Wendy; Mazurak, Vera

2008-01-01

An n-3 polyunsaturated fatty acid (PUFA) supplement was incorporated into three food products previously determined to be preferred by cancer patients, and overall acceptability of these foods was evaluated. Preliminary testing was performed; an internal panel determined initial acceptability of foods with the supplement added. Taste panel evaluations were held at the Cross Cancer Institute in Edmonton, Alberta. Each participant completed a questionnaire rating aroma, flavour, and overall acceptance on a seven-point hedonic scale (1 = dislike extremely, 7 = like extremely), as well as ability to consume each food daily. Foods were well-liked by patients and non-patients. Mean +/- standard deviation acceptance scores for the three foods were pasta sauce 5.9 +/- 0.94 (n=90), oatmeal 6.1 +/- 0.88 (n=79), and smoothie 5.9 +/- 1.12 (n=126). Overall, 94% of patients and non-patients gave tomato pasta sauce, oatmeal, and the smoothie an acceptance score of at least 5. The supplement was incorporated successfully into three foods, which were highly accepted by patients with cancer. Further research should focus on incorporating the supplement into flavoured or sweet foods, as these appear most effective. Microencapsulated fish oil in food products may be used as an alternative to fish oil capsules for delivering n-3 PUFA in clinical trials.
Omega 3 polyunsaturated fatty acids and body weight.

PubMed

Martínez-Victoria, Emilio; Yago, María Dolores

2012-06-01

In animal studies, n-3 PUFA have been shown to influence body composition and to reduce the accumulation of body fat, thereby affecting body weight homeostasis. In addition, it has been suggested that an additional supply of n-3 PUFA during pregnancy or lactation, or both, would have a beneficial effect on birth weight and infant growth and development. The purpose of the present study was to systematically review interventional clinical trials on the effects of dietary n-3 PUFA supplementation on body weight in adult subjects and in infants whose mothers were supplemented with these fatty acids during pregnancy and/or lactation. A systematic search, focused on n-3 PUFA and body weight, and limited to controlled clinical trials, was performed in different databases. The quality of all included studies was assessed against set criteria, and results of eligible trials were compared. There were few studies targeting this topic. In adults, all of the five studies included, except for one, show no change in body weight by dietary supplementation with n-3 PUFA. Within those trials conducted in pregnant and/or lactating women in which a main outcome was birth weight or growth in infancy, two showed a modest increase in birth weight and the rest showed no effect. None of the trials showed an effect of maternal n-3 PUFA supplementation on infant's weight at the short term. However, it should be noted that a number of limitations, including a variety of experimental designs, type and doses of n-3 PUFA, and high attrition rates, among others, make impossible to draw robust conclusions from this review.
Healthy n-6/n-3 fatty acid composition from five European game meat species remains after cooking.

PubMed

Valencak, Teresa G; Gamsjäger, Lisa; Ohrnberger, Sarah; Culbert, Nicole J; Ruf, Thomas

2015-06-27

Intensive farming of livestock along with recent food scandals and consumer deception have increased awareness about risks for human nutrition. In parallel, the demand for meat obtained under more natural conditions from animals that can freely forage has largely increased. Interestingly, the consumption of game meat has not become more common despite its excellent quality and content of polyunsaturated fatty acids (PUFAs). We addressed the question if game meat fatty acid composition is modified through kitchen preparation. By analysing muscle fatty acid (FA) composition (polar and total lipids) of five European game species in a raw and a processed state, we aimed to quantify the proportion of PUFA that are oxidised and hydrogenated during processing. All game meat species originated from local hunters and free-living individuals. To mimic a realistic situation a professional chef prepared the meat samples with gentle use of heat in a standardised way. Expectedly, the overall content of polyunsaturated fatty acids declined during the cooking process but the decrease size was <5% and the nutritiously most important n-3/n-6 ratio was not affected by processing (F1,54 = 0.46; p = 0.5). Generally, our samples contained species-specific high PUFA and n-3 FA contents but we point out that differentiating between species is necessary. Game meat thus provides a healthy meat source, as cooking does not substantially alter its favourable fatty acid composition. Further research is needed to elucidate species-specific differences and the role of habitat quality and locomotion for tissue composition.

Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice.

PubMed

Sapieha, P; Chen, J; Stahl, A; Seaward, M R; Favazza, T L; Juan, A M; Hatton, C J; Joyal, J-S; Krah, N M; Dennison, R J; Tang, J; Kern, T S; Akula, J D; Smith, L E H

2012-07-23

Diabetic retinopathy (DR) is associated with hyperglycemia-driven microvascular pathology and neuronal compromise in the retina. However, DR is also linked to dyslipidemia. As omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are protective in proliferative retinopathy, we investigated the capacity of ω-3PUFAs to preserve retinal function in a mouse model of type 2 diabetes mellitus (T2DM). Male leptin-receptor-deficient (db/db) mice were maintained for 22 weeks (4 weeks-26 weeks of life) on calorically and compositionally matched diets, except for 2% enrichment in either ω-3 or ω-6PUFAs. Visual function was assessed at 9, 14 and 26 weeks by electroretinography. Retinal capillary and neuronal integrity, as well as glucose challenge responses, were assessed on each diet. The ω-3PUFA diet significantly preserved retinal function in the mouse model of T2DM to levels similar to those observed in nondiabetic control mice on normal chow. Conversely, retinal function gradually deteriorated in db/db mice on a ω-6PUFA-rich diet. There was also an enhanced ability of ω-3PUFA-fed mice to respond to glucose challenge. The protection of visual function appeared to be independent of cytoprotective or anti-inflammatory effects of ω-3PUFAs. This study identifies beneficial effects of dietary ω-3PUFAs on visual function in T2DM. The data are consistent with dyslipidemia negatively impacting retinal function. As ω-3PUFA lipid dietary interventions are readily available, safe and inexpensive, increasing ω-3PUFA intake in diabetic patients may slow the progression of vision loss in T2DM.
Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice

PubMed Central

Sapieha, P; Chen, J; Stahl, A; Seaward, M R; Favazza, T L; Juan, A M; Hatton, C J; Joyal, J-S; Krah, N M; Dennison, R J; Tang, J; Kern, T S; Akula, J D; Smith, L E H

2012-01-01

Objective: Diabetic retinopathy (DR) is associated with hyperglycemia-driven microvascular pathology and neuronal compromise in the retina. However, DR is also linked to dyslipidemia. As omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are protective in proliferative retinopathy, we investigated the capacity of ω-3PUFAs to preserve retinal function in a mouse model of type 2 diabetes mellitus (T2DM). Design: Male leptin-receptor-deficient (db/db) mice were maintained for 22 weeks (4 weeks–26 weeks of life) on calorically and compositionally matched diets, except for 2% enrichment in either ω-3 or ω-6PUFAs. Visual function was assessed at 9, 14 and 26 weeks by electroretinography. Retinal capillary and neuronal integrity, as well as glucose challenge responses, were assessed on each diet. Results: The ω-3PUFA diet significantly preserved retinal function in the mouse model of T2DM to levels similar to those observed in nondiabetic control mice on normal chow. Conversely, retinal function gradually deteriorated in db/db mice on a ω-6PUFA-rich diet. There was also an enhanced ability of ω-3PUFA-fed mice to respond to glucose challenge. The protection of visual function appeared to be independent of cytoprotective or anti-inflammatory effects of ω-3PUFAs. Conclusion: This study identifies beneficial effects of dietary ω-3PUFAs on visual function in T2DM. The data are consistent with dyslipidemia negatively impacting retinal function. As ω-3PUFA lipid dietary interventions are readily available, safe and inexpensive, increasing ω-3PUFA intake in diabetic patients may slow the progression of vision loss in T2DM. PMID:23448719
Effects of dietary omega-3/omega-6 fatty acid ratios on reproduction in the young breeder rooster.

PubMed

Feng, Yun; Ding, Yu; Liu, Juan; Tian, Ye; Yang, Yanzhou; Guan, Shuluan; Zhang, Cheng

2015-03-21

Polyunsaturated fatty acids (PUFAs) are necessary for the body's metabolism, growth and development. Although PUFAs play an important role in the regulation of reproduction, their role in testis development in the rooster is unknown. The present study was conducted to investigate the effects of omega-3/omega-6 (n-3/n-6, PUFAs) ratios on reproductive performance in young breeder roosters. Plasma levels of reproductive hormones, testis development, and reproductive hormone receptor and StAR mRNA expression were also assessed. Although PUFAs (n-3/n-6: 1/4.15) had no significant effect on the testis index (P > 0.05), the spermatogonial development and germ cell layers were increased. Moreover, serum levels of hormones (GnRH, FSH, LH and T) on day 35 were also significantly increased by PUFAs (n-3/n-6: 1/4.15). To investigate whether PUFAs regulate the expression of hormone receptors and StAR, real time-PCR was used to measure GnRHR, FSHR, LHR and StAR mRNA levels. PUFAs significantly increased the mRNA levels of all of these genes. These results indicate that PUFAs enhance the reproductive performance of young roosters by increasing hormone secretion and function, the latter by up-regulating receptor expression. These findings provide a sound basis for a balanced n-3/n-6 PUFA ratio being beneficial to young rooster reproduction.
Fatty acid supply with complementary foods and LC-PUFA status in healthy infants: results of a randomised controlled trial.

PubMed

Libuda, Lars; Mesch, Christina M; Stimming, Madlen; Demmelmair, Hans; Koletzko, Berthold; Warschburger, Petra; Blanke, Katharina; Reischl, Eva; Kalhoff, Hermann; Kersting, Mathilde

2016-06-01

Introduction of complementary food usually leads to decreasing intakes of long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFA), compared to full breastfeeding. In the randomised controlled PINGU intervention trial, we tested the effects of complementary foods with different contents of alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) on term infant LC-PUFA status. Healthy infants born at term were randomised to receive from the introduction of complementary feeding at the age of 4 to 6 months until age of 10 months ready-made complementary meals either with ALA-rich rapeseed oil (intervention group (IG)-R), with salmon twice weekly to provide preformed DHA (IG-F), or with linoleic acid-rich corn oil (control group, CG). Fatty acid composition was assessed in erythrocyte (RBC) and plasma glycerophospholipids. Complete data of fatty acids in RBC (plasma) were available from 158 (155) infants. After intervention, infants assigned to IG-F showed higher RBC and plasma percentages of eicosapentaenoic acid (EPA), DHA, and total n-3 LC-PUFA than CG (each p < 0.001). In IG-R, levels of ALA and the ratio of ALA to LA in plasma and RBC (all p < 0.0001) as well as RBC-EPA (p < 0.0001) were higher than in CG, while DHA levels did not differ between IG-R and CG. Regular fish consumption during complementary feeding enhances infant EPA and DHA status. The usage of rapeseed oil in small amounts concordant with EU-law for commercial meals enhances endogenic EPA-synthesis, but does not affect DHA status. Provision of oily fish with complementary feeds is advisable to prevent a decline of DHA status. www.clinicaltrials.gov , identifier: NCT01487889, title: Polyunsaturated fatty acids in child nutrition-a German multimodal optimisation study (PINGU).
Botanical oils enriched in n-6 and n-3 FADS2 products are equally effective in preventing atherosclerosis and fatty liver.

PubMed

Shewale, Swapnil V; Boudyguina, Elena; Zhu, Xuewei; Shen, Lulu; Hutchins, Patrick M; Barkley, Robert M; Murphy, Robert C; Parks, John S

2015-06-01

Echium oil (EO), which is enriched in 18:4 n-3, the immediate product of fatty acid desaturase 2 (FADS2) desaturation of 18:3 n-3, is as atheroprotective as fish oil (FO). The objective of this study was to determine whether botanical oils enriched in the FADS2 products 18:3 n-6 versus 18:4 n-3 are equally atheroprotective. LDL receptor KO mice were fed one of four atherogenic diets containing 0.2% cholesterol and 10% calories as palm oil (PO) plus 10% calories as: 1) PO; 2) borage oil (BO; 18:3 n-6 enriched); 3) EO (18:4 n-3 enriched); or 4) FO for 16 weeks. Mice fed BO, EO, and FO versus PO had significantly lower plasma total and VLDL cholesterol concentrations; hepatic neutral lipid content and inflammation, aortic CE content, aortic root intimal area and macrophage content; and peritoneal macrophage inflammation, CE content, and ex vivo chemotaxis. Atheromas lacked oxidized CEs despite abundant generation of macrophage 12/15 lipooxygenase-derived metabolites. We conclude that botanical oils enriched in 18:3 n-6 and 18:4 n-3 PUFAs beyond the rate-limiting FADS2 enzyme are equally effective in preventing atherosclerosis and hepatosteatosis compared with saturated/monounsaturated fat due to cellular enrichment of ≥20 PUFAs, reduced plasma VLDL, and attenuated macrophage inflammation. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.
Comparative Study of Different Polar Groups of EPA-Enriched Phospholipids on Ameliorating Memory Loss and Cognitive Deficiency in Aged SAMP8 Mice.

PubMed

Zhou, Miao-Miao; Che, Hong-Xia; Huang, Jia-Qi; Zhang, Tian-Tian; Xu, Jie; Xue, Chang-Hu; Wang, Yu-Ming

2018-04-01

Recent studies have shown that omega-3 PUFAs enriched phospholipids (n-3 PUFA-PLs) have beneficial effects on memory and cognition. However, most reports only attribute the benefit to docosahexaenoic acid (DHA) and pay little attention to eicosapentaenoic acid (EPA). We investigate the effect of EPA-enriched phospholipids on cognitive deficiency in senescence-accelerated prone 8 (SAMP8) mouse. Ten-month-old SAMP8 mice are fed with 2% (w/w) EPA-enriched phosphatidylcholine/phosphatidyl ethanolamine (EPA-PC/PE; EPA:DHA = 46.8:3.01) or 2% EPA-enriched phosphatidylserine (EPA-PS; biosynthesized from EPA-PC/PE) for 8 weeks; we then test the behavioral performances in the Barnes maze test and Morris maze test; the changes of oxidative stress, apoptosis, neurotrophic factors, tau phosphorylation, and Aβ pathology are also measured. The results of behavior tests indicate that both EPA-PC/PE and EPA-PS significantly improve memory and cognitive deficiency. It is found that remarkable amelioration of oxidative stress and apoptosis occurs in both EPA-PC/PE and EPA-PS groups. EPA-PS shows more ameliorative effects than EPA-PC/PE on neurotrophic activity by decreasing hyper-phosphorylation of tau and depressing the generation and accumulation of β-amyloid peptide (Aβ). These data suggest that EPA-PS exhibits better effects than EPA-PC/PE on ameliorating memory and cognitive function, which might be attributed to the phospholipid polar groups. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Nutrition and Inflammation in Older Individuals: Focus on Vitamin D, n-3 Polyunsaturated Fatty Acids and Whey Proteins.

PubMed

Ticinesi, Andrea; Meschi, Tiziana; Lauretani, Fulvio; Felis, Giovanna; Franchi, Fabrizio; Pedrolli, Carlo; Barichella, Michela; Benati, Giuseppe; Di Nuzzo, Sergio; Ceda, Gian Paolo; Maggio, Marcello

2016-03-29

Chronic activation of the inflammatory response, defined as inflammaging, is the key physio-pathological substrate for anabolic resistance, sarcopenia and frailty in older individuals. Nutrients can theoretically modulate this phenomenon. The underlying molecular mechanisms reducing the synthesis of pro-inflammatory mediators have been elucidated, particularly for vitamin D, n-3 polyunsaturated fatty acids (PUFA) and whey proteins. In this paper, we review the current evidence emerging from observational and intervention studies, performed in older individuals, either community-dwelling or hospitalized with acute disease, and evaluating the effects of intake of vitamin D, n-3 PUFA and whey proteins on inflammatory markers, such as C-Reactive Protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). After the analysis, we conclude that there is sufficient evidence for an anti-inflammatory effect in aging only for n-3 PUFA intake, while the few existing intervention studies do not support a similar activity for vitamin D and whey supplements. There is need in the future of large, high-quality studies testing the effects of combined dietary interventions including the above mentioned nutrients on inflammation and health-related outcomes.
Nutrition and Inflammation in Older Individuals: Focus on Vitamin D, n-3 Polyunsaturated Fatty Acids and Whey Proteins

PubMed Central

Ticinesi, Andrea; Meschi, Tiziana; Lauretani, Fulvio; Felis, Giovanna; Franchi, Fabrizio; Pedrolli, Carlo; Barichella, Michela; Benati, Giuseppe; Di Nuzzo, Sergio; Ceda, Gian Paolo; Maggio, Marcello

2016-01-01

Chronic activation of the inflammatory response, defined as inflammaging, is the key physio-pathological substrate for anabolic resistance, sarcopenia and frailty in older individuals. Nutrients can theoretically modulate this phenomenon. The underlying molecular mechanisms reducing the synthesis of pro-inflammatory mediators have been elucidated, particularly for vitamin D, n-3 polyunsaturated fatty acids (PUFA) and whey proteins. In this paper, we review the current evidence emerging from observational and intervention studies, performed in older individuals, either community-dwelling or hospitalized with acute disease, and evaluating the effects of intake of vitamin D, n-3 PUFA and whey proteins on inflammatory markers, such as C-Reactive Protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). After the analysis, we conclude that there is sufficient evidence for an anti-inflammatory effect in aging only for n-3 PUFA intake, while the few existing intervention studies do not support a similar activity for vitamin D and whey supplements. There is need in the future of large, high-quality studies testing the effects of combined dietary interventions including the above mentioned nutrients on inflammation and health-related outcomes. PMID:27043616
Postprandial lipid responses do not differ following consumption of butter or vegetable oil when consumed with omega-3 polyunsaturated fatty acids.

PubMed

Dias, Cintia B; Phang, Melinda; Wood, Lisa G; Garg, Manohar L

2015-04-01

Dietary saturated fat (SFA) intake has been associated with elevated blood lipid levels and increased risk for the development of chronic diseases. However, some animal studies have demonstrated that dietary SFA may not raise blood lipid levels when the diet is sufficient in omega-3 polyunsaturated fatty acids (n-3PUFA). Therefore, in a randomised cross-over design, we investigated the postprandial effects of feeding meals rich in either SFA (butter) or vegetable oil rich in omega-6 polyunsaturated fatty acids (n-6PUFA), in conjunction with n-3PUFA, on blood lipid profiles [total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triacylglycerol (TAG)] and n-3PUFA incorporation into plasma lipids over a 6-h period. The incremental area under the curve for plasma cholesterol, LDL-C, HDL-C, TAG and n-3PUFA levels over 6 h was similar in the n-6PUFA compared to SFA group. The postprandial lipemic response to saturated fat is comparable to that of n-6PUFA when consumed with n-3PUFA; however, sex-differences in response to dietary fat type are worthy of further attention.
Docosahexaenoic Acid (DHA) and Hepatic Gene Transcription1,3

PubMed Central

Jump, Donald B.; Botolin, Daniela; Wang, Yun; Xu, Jinghua; Demeure, Olivier; Christian, Barbara

2008-01-01

The type and quantity of dietary fat ingested contributes to the onset and progression of chronic diseases, like diabetes and atherosclerosis. The liver plays a central role in whole body lipid metabolism and responds rapidly to changes in dietary fat composition. Polyunsaturated fatty acids (PUFA) play a key role in membrane composition and function, metabolism and the control of gene expression. Certain PUFA, like the n-3 PUFA, enhance hepatic fatty acid oxidation and inhibit fatty acid synthesis and VLDL secretion, in part, by regulating gene expression. Our studies have established that key transcription factors, like PPARα, SREBP-1, ChREBP and MLX, are regulated by n-3 PUFA, which in turn control levels of proteins involved in lipid and carbohydrate metabolism. Of the n-3 PUFA, 22:6,n-3 has recently been established as a key controller of hepatic lipid synthesis. 22:6,n-3 controls the 26S proteasomal degradation of the nuclear form of SREBP-1. SREBP-1 is a major transcription factor that controls the expression of multiple genes involved fatty acid synthesis and desaturation. 22:6,n-3 suppresses nuclear SREBP-1 which, in turn suppresses lipogenesis. This mechanism is achieved, in part, through control of the phosphorylation status of protein kinases. This review will examine both the general features of PUFA-regulated hepatic gene transcription and highlight the unique mechanisms by which 22:6,n-3 impacts gene expression. The outcome of this analysis will reveal that changes in hepatic 22:6,n-3 content has a major impact on hepatic lipid and carbohydrate metabolism. Moreover, the mechanisms involve 22:6,n-3 control of several well-known signaling pathways, such as Akt, Erk1/2, Gsk3β and PKC (novel or atypical). 22:6,n-3 control of these same signaling pathways in non-hepatic tissues may help explain the diverse actions of n-3 PUFA on such complex physiological processes as visual acuity and learning. PMID:18343222
Dietary Patterns, n-3 Fatty Acids Intake from Seafood and High Levels of Anxiety Symptoms during Pregnancy: Findings from the Avon Longitudinal Study of Parents and Children

PubMed Central

Vaz, Juliana dos Santos; Kac, Gilberto; Emmett, Pauline; Davis, John M.; Golding, Jean; Hibbeln, Joseph R.

2013-01-01

Background Little is known about relationships between dietary patterns, n-3 polyunsaturated fatty acids (PUFA) intake and excessive anxiety during pregnancy. Objective To examine whether dietary patterns and n-3 PUFA intake from seafood are associated with high levels of anxiety during pregnancy. Design Pregnant women enrolled from 1991–1992 in ALSPAC (n 9,530). Dietary patterns were established from a food frequency questionnaire using principal component analysis. Total intake of n-3 PUFA (grams/week) from seafood was also examined. Symptoms of anxiety were measured at 32 weeks of gestation with the Crown-Crisp Experiential Index; scores ≥9 corresponding to the 85th percentile was defined as high anxiety symptoms. Multivariate logistic regression models were used to estimate the OR and 95% CI, adjusted by socioeconomic and lifestyle variables. Results Multivariate results showed that women in the highest tertile of the health-conscious (OR 0.77; 0.65–0.93) and the traditional (OR 0.84; 0.73–0.97) pattern scores were less likely to report high levels of anxiety symptoms. Women in the highest tertile of the vegetarian pattern score (OR 1.25; 1.08–1.44) were more likely to have high levels of anxiety, as well as those with no n-3 PUFA intake from seafood (OR 1.53; 1.25–1.87) when compared with those with intake of >1.5 grams/week. Conclusions The present study provides evidence of a relationship between dietary patterns, fish intake or n-3 PUFA intake from seafood and symptoms of anxiety in pregnancy, and suggests that dietary interventions could be used to reduce high anxiety symptoms during pregnancy. PMID:23874437
Evaluation of phosphorus, protein, and n-3 fatty-acid content in 15 marine fish species identifies the species most beneficial to renal patients.

PubMed

Castro-Gonzalez, Isabel; Miranda-Becerra, Daniela; Montano-Benavides, Sara

2009-11-01

Among 15 marine fish species, we sought to identify those most beneficial to renal patients by evaluating their phosphorus (P), protein (PC), and n-3 fatty-acid (n-3 PUFA) content. These 15 species are all edible. They were obtained and sampled randomly, and were filleted to obtain 100g, enabling us to perform the analysis in triplicate. Crude protein was analyzed with a Kjeltec, and minerals were analyzed using atomic absorption spectrophotometry. The PC values (g/100g) ranged from 14.3 (blue runner; BR) to 22.8 (California butterfly ray). The fish with the highest P (mg/100g) content were spotted sea trout (ST), gafftopsail fish (CF) (289), and BR (274), followed by smalltail shark (272). The species with the lowest ratio of P:n-3 PUFA was dollar fish (DF) (0.28), followed by BR, ST, and vermilion snapper (range, 0.28 to 0.67). The highest ratio of P:n-3 PUFA was found in the small-tail shark (11.6). Fish with a high n-3 PUFA/g PC content were DF (41.7), BR (38.05), ST (34.8), and CF (22.5). There was a tendency of P to increase as muscle fat increased (mg P/100g), i.e., lean fish (194), semifatty fish (239), and fatty fish (262). The regular inclusion in the diet, at least three times a week, of the species DF, BR, CF, ST, caitipa mojarra, vermillion snapper, and pot snapper can be considered beneficial to the general health status of renal patients.
Alterations in neuronal morphology and synaptophysin expression in the rat brain as a result of changes in dietary n-6: n-3 fatty acid ratios.

PubMed

Hajjar, Toktam; Goh, Yong Meng; Rajion, Mohamed Ali; Vidyadaran, Sharmili; Li, Tan Ai; Ebrahimi, Mahdi

2013-07-26

Polyunsaturated fatty acids (PUFA) play important roles in brain fatty acid composition and behavior through their effects on neuronal properties and gene expression. The hippocampus plays an important role in the formation of memory, especially spatial memory and navigation. This study was conducted to examine the effects of PUFA and specifically different dietary n-6: n-3 fatty acid ratios (FAR) on the number and size of hippocampal neurons and the expression of synaptophysin protein in the hippocampus of rats. Forty 3-week old male Sprague-Dawley rats were allotted into 4 groups. The animals received experimental diets with different n-6: n-3 FAR of either 65:1, 26.5:1, 22:1 or 4.5:1 for 14 weeks. The results showed that a lowering dietary n-6: n-3 FAR supplementation can increase the number and size of neurons. Moreover, lowering the dietary n-6: n-3 FAR led to an increase in the expression of the pre-synaptic protein synaptophysin in the CA1 hippocampal subregion of the rat brain. These findings support the notion that decreasing the dietary n-6: n-3 FAR will lead to an intensified hippocampal synaptophysin expression and increased neuron size and proliferation in the rat brain.
Modulation of the endogenous omega-3 fatty acid and oxylipin profile in vivo-A comparison of the fat-1 transgenic mouse with C57BL/6 wildtype mice on an omega-3 fatty acid enriched diet.

PubMed

Ostermann, Annika I; Waindok, Patrick; Schmidt, Moritz J; Chiu, Cheng-Ying; Smyl, Christopher; Rohwer, Nadine; Weylandt, Karsten-H; Schebb, Nils Helge

2017-01-01

Dietary intervention and genetic fat-1 mice are two models for the investigation of effects associated with omega-3 polyunsaturated fatty acids (n3-PUFA). In order to assess their power to modulate the fatty acid and oxylipin pattern, we thoroughly compared fat-1 and wild-type C57BL/6 mice on a sunflower oil diet with wild-type mice on the same diet enriched with 1% EPA and 1% DHA for 0, 7, 14, 30 and 45 days. Feeding led after 14-30 days to a high steady state of n3-PUFA in all tissues at the expense of n6-PUFAs. Levels of n3-PUFA achieved by feeding were higher compared to fat-1 mice, particularly for EPA (max. 1.7% in whole blood of fat-1 vs. 7.8% following feeding). Changes in PUFAs were reflected in most oxylipins in plasma, brain and colon: Compared to wild-type mice on a standard diet, arachidonic acid metabolites were overall decreased while EPA and DHA oxylipins increased with feeding more than in fat-1 mice. In plasma of n3-PUFA fed animals, EPA and DHA metabolites from the lipoxygenase and cytochrome P450 pathways dominated over ARA derived counterparts.Fat-1 mice show n3-PUFA level which can be reached by dietary interventions, supporting the applicability of this model in n3-PUFA research. However, for specific questions, e.g. the role of EPA derived mediators or concentration dependent effects of (individual) PUFA, feeding studies are necessary.
Hypothalamic fatty acid sensing in Senegalese sole (Solea senegalensis): response to long-chain saturated, monounsaturated, and polyunsaturated (n-3) fatty acids.

PubMed

Conde-Sieira, Marta; Bonacic, Kruno; Velasco, Cristina; Valente, Luisa M P; Morais, Sofia; Soengas, José L

2015-12-15

We assessed the presence of fatty acid (FA)-sensing mechanisms in hypothalamus of Senegalese sole (Solea senegalensis) and investigated their sensitivity to FA chain length and/or level of unsaturation. Stearate (SA, saturated FA), oleate (OA, monounsaturated FA of the same chain length), α-linolenate [ALA, a n-3 polyunsaturated fatty acid (PUFA) of the same chain length], and eicosapentanoate (EPA, a n-3 PUFA of a larger chain length) were injected intraperitoneally. Parameters related to FA sensing and neuropeptide expression in the hypothalamus were assessed after 3 h and changes in accumulated food intake after 4, 24, and 48 h. Three FA sensing systems characterized in rainbow trout were also found in Senegalese sole and were activated by OA in a way similar to that previously characterized in rainbow trout and mammals. These hypothalamic FA sensing systems were also activated by ALA, differing from mammals, where n-3 PUFAs do not seem to activate FA sensors. This might suggest additional roles and highlights the importance of n-3 PUFA in fish diets, especially in marine species. The activation of FA sensing seems to be partially dependent on acyl chain length and degree of saturation, as no major changes were observed after treating fish with SA or EPA. The activation of FA sensing systems by OA and ALA, but not SA or EPA, is further reflected in the expression of hypothalamic neuropeptides involved in the control of food intake. Both OA and ALA enhanced anorexigenic capacity compatible with the activation of FA sensing systems. Copyright © 2015 the American Physiological Society.
Changes in Fatty Acid Composition and Distribution of N-3 Fatty Acids in Goat Tissues Fed Different Levels of Whole Linseed

PubMed Central

Zakaria, Md. Zuki Abu Bakar; Meng, Goh Yong; Sazili, Awis Qurni

2014-01-01

The effects of feeding different levels of whole linseed on fatty acid (FA) composition of muscles and adipose tissues of goat were investigated. Twenty-four Crossed Boer bucks were assigned randomly into three treatment diets: L0, L10, or L20, containing 0%, 10%, or 20% whole linseed, respectively. The goats were slaughtered after 110 days of feeding. Samples from the longissimus dorsi, supraspinatus, semitendinosus, and subcutaneous fat (SF) and perirenal fat (PF) were taken for FA analyses. In muscles, the average increments in α-linolenic (ALA) and total n-3 PUFA were 6.48 and 3.4, and 11.48 and 4.78 for L10 and L20, respectively. In the adipose tissues, the increments in ALA and total n-3 PUFA were 3.07- and 6.92-fold and 3.00- and 7.54-fold in SF and PF for L10 and L20, respectively. The n-6 : n-3 ratio of the muscles was decreased from up to 8.86 in L0 to 2 or less in L10 and L20. The PUFA : SFA ratio was increased in all the tissues of L20 compared to L0. It is concluded that both inclusion levels (10% and 20%) of whole linseed in goat diets resulted in producing meat highly enriched with n-3 PUFA with desirable n-6 : n-3 ratio. PMID:25478601
Co-Enzyme Q10 and n-3 Polyunsaturated Fatty Acid Supplementation Reverse Intermittent Hypoxia-Induced Growth Restriction and Improved Antioxidant Profiles in Neonatal Rats.

PubMed

Beharry, Kay D; Cai, Charles L; Henry, Michael M; Chowdhury, Sara; Valencia, Gloria B; Aranda, Jacob V

2017-12-16

Neonatal intermittent hypoxia (IH) increases the risk for many morbidities in extremely low birth weight/gestational age (ELBW/ELGA) neonates with compromised antioxidant systems and poor growth. We hypothesized that supplementation with coenzyme Q10 (CoQ10, ubiquinol) or n -3 polyunsaturated fatty acids (PUFAs) during neonatal IH improves antioxidant profiles and somatic growth in neonatal rats. Newborn rats were exposed to two IH paradigms at birth (P0): (1) 50% O₂ with brief hypoxic episodes (12% O₂); or (2) room air (RA) with brief hypoxia, until P14 during which they received daily oral CoQ10 in olive oil, n -3 PUFAs in fish oil, or olive oil only from P0 to P14. Pups were studied at P14 or placed in RA until P21 for recovery from IH (IHR). Body weight and length; organ weights; and serum antioxidants and growth factors were determined at P14 and P21. Neonatal IH resulted in sustained reductions in somatic growth, an effect that was reversed with n -3 PUFAs. Improved growth was associated with higher serum growth factors. CoQ10 decreased superoxide dismutase (SOD) and glutathione, but increased catalase, suggesting reduced oxidative stress. Further studies are needed to determine the synergistic effects of CoQ10 and n -3 PUFA co-administration for the prevention of IH-induced oxidative stress and postnatal growth deficits.
Omega-3 polyunsaturated fatty acids ameliorate neuroinflammation and mitigate ischemic stroke damage through interactions with astrocytes and microglia.

PubMed

Zendedel, Adib; Habib, Pardes; Dang, Jon; Lammerding, Leoni; Hoffmann, Stefanie; Beyer, Cordian; Slowik, Alexander

2015-01-15

Omega-3 polyunsaturated fatty acids (PUFA n3) provide neuroprotection due to their anti-inflammatory and anti-apoptotic properties as well as their regulatory function on growth factors and neuronal plasticity. These qualities enable PUFA n3 to ameliorate stroke outcome and limit neuronal damage. Young adult male rats received transient middle cerebral artery occlusion (tMCAO). PUFA n3 were intravenously administered into the jugular vein immediately after stroke and 12h later. We analyzed stroke volume and behavioral performance as well as the regulation of functionally-relevant genes in the penumbra. The extent of ischemic damage was reduced and behavioral performance improved subject to applied PUFA n3. Expression of Tau and growth-associated protein-43 genes were likewise restored. Ischemia-induced increase of cytokine mRNA levels was abated by PUFA n3. Using an in vitro approach, we demonstrate that cultured astroglial and microglia directly respond to PUFA n3 administration by preventing ischemia-induced increase of cyclooxygenase 2, hypoxia-inducible factor 1alpha, inducible nitric oxide synthase, and interleukin 1beta. Cultured cortical neurons also appeared as direct targets, since PUFA n3 shifted the Bcl-2-like protein 4 (Bax)/B-cell lymphoma 2 (Bcl 2) ratio towards an anti-apoptotic constellation. Thus, PUFA n3 reveal a high neuroprotective and anti-inflammatory potential in an acute ischemic stroke model by targeting astroglial and microglial function as well as improving neuronal survival strategies. Our findings signify the potential clinical feasibility of PUFA n3 therapeutic treatment in stroke and other acute neurological diseases. Copyright © 2014 Elsevier B.V. All rights reserved.
A Metabolomic Analysis of Omega-3 Fatty Acid-Mediated Attenuation of Western Diet-Induced Nonalcoholic Steatohepatitis in LDLR -/- Mice

PubMed Central

Depner, Christopher M.; Traber, Maret G.; Bobe, Gerd; Kensicki, Elizabeth; Bohren, Kurt M.; Milne, Ginger; Jump, Donald B.

2013-01-01

Background Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease and a risk factor for cirrhosis, hepatocellular carcinoma and liver failure. Previously, we reported that dietary docosahexaenoic acid (DHA, 22:6,n-3) was more effective than eicosapentaenoic acid (EPA, 20:5,n-3) at reversing western diet (WD) induced NASH in LDLR-/- mice. Methods Using livers from our previous study, we carried out a global non-targeted metabolomic approach to quantify diet-induced changes in hepatic metabolism. Results Livers from WD + olive oil (WD + O)-fed mice displayed histological and gene expression features consistent with NASH. The metabolomic analysis of 320 metabolites established that the WD and n-3 polyunsaturated fatty acid (PUFA) supplementation had broad effects on all major metabolic pathways. Livers from WD + O-fed mice were enriched in saturated (SFA) and monounsaturated fatty acids (MUFA), palmitoyl-sphingomyelin, cholesterol, n-6 PUFA, n-6 PUFA-containing phosphoglycerolipids, n-6 PUFA-derived oxidized lipids (12-HETE) and depleted of C20-22 n-3 PUFA-containing phosphoglycerolipids, C20-22 n-3 PUFA-derived oxidized lipids (18-HEPE, 17,18-DiHETE) and S-lactoylglutathione, a methylglyoxal detoxification product. WD + DHA was more effective than WD + EPA at attenuating WD + O-induced changes in NASH gene expression markers, n-6 PUFA and oxidized lipids, citrate and S-lactosyl glutathione. Diet-induced changes in hepatic MUFA and sphingolipid content were associated with changes in expression of enzymes involved in MUFA and sphingolipid synthesis. Changes in hepatic oxidized fatty acids and S-lactoylglutathione, however, correlated with hepatic n-3 and n-6 C20-22 PUFA content. Hepatic C20-22 n-3 PUFA content was inversely associated with hepatic α-tocopherol and ascorbate content and positively associated with urinary F2- and F3-isoprostanes, revealing diet effects on whole body oxidative stress. Conclusion DHA regulation of
A metabolomic analysis of omega-3 fatty acid-mediated attenuation of western diet-induced nonalcoholic steatohepatitis in LDLR-/- mice.

PubMed

Depner, Christopher M; Traber, Maret G; Bobe, Gerd; Kensicki, Elizabeth; Bohren, Kurt M; Milne, Ginger; Jump, Donald B

2013-01-01

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease and a risk factor for cirrhosis, hepatocellular carcinoma and liver failure. Previously, we reported that dietary docosahexaenoic acid (DHA, 22:6,n-3) was more effective than eicosapentaenoic acid (EPA, 20:5,n-3) at reversing western diet (WD) induced NASH in LDLR(-/-) mice. Using livers from our previous study, we carried out a global non-targeted metabolomic approach to quantify diet-induced changes in hepatic metabolism. Livers from WD + olive oil (WD + O)-fed mice displayed histological and gene expression features consistent with NASH. The metabolomic analysis of 320 metabolites established that the WD and n-3 polyunsaturated fatty acid (PUFA) supplementation had broad effects on all major metabolic pathways. Livers from WD + O-fed mice were enriched in saturated (SFA) and monounsaturated fatty acids (MUFA), palmitoyl-sphingomyelin, cholesterol, n-6 PUFA, n-6 PUFA-containing phosphoglycerolipids, n-6 PUFA-derived oxidized lipids (12-HETE) and depleted of C20-22 n-3 PUFA-containing phosphoglycerolipids, C20-22 n-3 PUFA-derived oxidized lipids (18-HEPE, 17,18-DiHETE) and S-lactoylglutathione, a methylglyoxal detoxification product. WD + DHA was more effective than WD + EPA at attenuating WD + O-induced changes in NASH gene expression markers, n-6 PUFA and oxidized lipids, citrate and S-lactosyl glutathione. Diet-induced changes in hepatic MUFA and sphingolipid content were associated with changes in expression of enzymes involved in MUFA and sphingolipid synthesis. Changes in hepatic oxidized fatty acids and S-lactoylglutathione, however, correlated with hepatic n-3 and n-6 C20-22 PUFA content. Hepatic C20-22 n-3 PUFA content was inversely associated with hepatic α-tocopherol and ascorbate content and positively associated with urinary F2- and F3-isoprostanes, revealing diet effects on whole body oxidative stress. DHA regulation of hepatic SFA, MUFA, PUFA

Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.

PubMed

Lemaitre, Rozenn N; Tanaka, Toshiko; Tang, Weihong; Manichaikul, Ani; Foy, Millennia; Kabagambe, Edmond K; Nettleton, Jennifer A; King, Irena B; Weng, Lu-Chen; Bhattacharya, Sayanti; Bandinelli, Stefania; Bis, Joshua C; Rich, Stephen S; Jacobs, David R; Cherubini, Antonio; McKnight, Barbara; Liang, Shuang; Gu, Xiangjun; Rice, Kenneth; Laurie, Cathy C; Lumley, Thomas; Browning, Brian L; Psaty, Bruce M; Chen, Yii-Der I; Friedlander, Yechiel; Djousse, Luc; Wu, Jason H Y; Siscovick, David S; Uitterlinden, André G; Arnett, Donna K; Ferrucci, Luigi; Fornage, Myriam; Tsai, Michael Y; Mozaffarian, Dariush; Steffen, Lyn M

2011-07-01

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10⁻⁶⁴) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10⁻⁵⁸) and docosapentaenoic acid (DPA, p = 4 x 10⁻¹⁵⁴). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10⁻¹²) and DPA (p = 1 x 10⁻⁴³) and lower docosahexaenoic acid (DHA, p = 1 x 10⁻¹⁵). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10⁻⁸). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.
Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE Consortium

PubMed Central

Kabagambe, Edmond K.; Nettleton, Jennifer A.; King, Irena B.; Weng, Lu-Chen; Bhattacharya, Sayanti; Bandinelli, Stefania; Bis, Joshua C.; Rich, Stephen S.; Jacobs, David R.; Cherubini, Antonio; McKnight, Barbara; Liang, Shuang; Gu, Xiangjun; Rice, Kenneth; Laurie, Cathy C.; Lumley, Thomas; Browning, Brian L.; Psaty, Bruce M.; Chen, Yii-Der I.; Friedlander, Yechiel; Djousse, Luc; Wu, Jason H. Y.; Siscovick, David S.; Uitterlinden, André G.; Arnett, Donna K.; Ferrucci, Luigi; Fornage, Myriam; Tsai, Michael Y.; Mozaffarian, Dariush; Steffen, Lyn M.

2011-01-01

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3×10−64) and lower levels of eicosapentaenoic acid (EPA, p = 5×10−58) and docosapentaenoic acid (DPA, p = 4×10−154). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10−12) and DPA (p = 1×10−43) and lower docosahexaenoic acid (DHA, p = 1×10−15). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1×10−8). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries. PMID:21829377
Restoration of fillet n-3 long-chain polyunsaturated fatty acid is improved by a modified fish oil finishing diet strategy for atlantic salmon (Salmo salar L.) smolts fed palm fatty acid distillate.

PubMed

Codabaccus, Mohamed B; Bridle, Andrew R; Nichols, Peter D; Carter, Chris G

2012-01-11

Reducing the lipid content in fish prior to feeding a fish oil finishing diet (FOFD) has the potential to improve n-3 long-chain (≥ C(20)) polyunsaturated fatty acid (LC-PUFA) restoration. This study had two main objectives: (1) determine whether feeding Atlantic salmon smolt a 75% palm fatty acid distillate diet (75PFAD) improves the apparent digestibility (AD) of saturated fatty acids (SFA) and (2) examine whether a food deprivation period after growth on 75PFAD leads to higher n-3 LC-PUFA restoration in the fillet when applying a FOFD. The AD of SFA was higher for 75PFAD compared to that of a fish oil (FO) diet. The relative level (as % total fatty acids (FA)) of n-3 LC-PUFA was higher in unfed fish compared to that in continuously fed fish after 21 and 28 day FOFD periods, respectively. Our results suggest that a food deprivation period prior to feeding a FOFD improves the efficiency of n-3 LC-PUFA restoration in the fillet of Atlantic salmon smolt.
Nutrition and the psychoneuroimmunology of postpartum depression.

PubMed

Ellsworth-Bowers, E R; Corwin, E J

2012-06-01

Postpartum depression (PPD) is a relatively common and often severe mood disorder that develops in women after childbirth. The aetiology of PPD is unclear, although there is emerging evidence to suggest a psychoneuroimmune connection. Additionally, deficiencies in n-3 PUFA, B vitamins, vitamin D and trace minerals have been implicated. This paper reviews evidence for a link between micronutrient status and PPD, analysing the potential contribution of each micronutrient to psychoneuroimmunological mechanisms of PPD. Articles related to PPD and women's levels of n-3 PUFA, B vitamins, vitamin D and the trace minerals Zn and Se were reviewed. Findings suggest that while n-3 PUFA levels have been shown to vary inversely with PPD and link with psychoneuroimmunology, there is mixed evidence regarding the ability of n-3 PUFA to prevent or treat PPD. B vitamin status is not clearly linked to PPD, even though it seems to vary inversely with depression in non-perinatal populations and may have an impact on immunity. Vitamin D and the trace minerals Zn and Se are linked to PPD and psychoneuroimmunology by intriguing, but small, studies. Overall, evidence suggests that certain micronutrient deficiencies contribute to the development of PPD, possibly through psychoneuroimmunological mechanisms. Developing a better understanding of these mechanisms is important for guiding future research, clinical practice and health education regarding PPD.
Different sources of omega-3 polyunsaturated fatty acids affects apparent digestibility, tissue deposition, and tissue oxidative stability in growing female rats.

PubMed

Tou, Janet C; Altman, Stephanie N; Gigliotti, Joseph C; Benedito, Vagner A; Cordonier, Elizabeth L

2011-10-14

Numerous health benefits associated with increased omega-3 polyunsaturated fatty acid (n-3 PUFA) consumption has lead to an increasing variety of available n-3 PUFA sources. However, sources differ in the type, amount, and structural form of the n-3 PUFAs. Therefore, the objective of this study was to determine the effect of different sources of ω-3 PUFAs on digestibility, tissue deposition, eicosanoid metabolism, and oxidative stability. Female Sprague-Dawley rats (age 28 d) were randomly assigned (n = 10/group) to be fed a high fat 12% (wt) diet consisting of either corn oil (CO) or n-3 PUFA rich flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) oil for 8 weeks. Rats were individually housed in metabolic cages to determine fatty acid digestibility. Diet and tissue fatty acid composition was analyzed by gas chromatography and lipid classes using thin layer chromatography. Eicosanoid metabolism was determined by measuring urinary metabolites of 2-series prostaglandins (PGs) and thromoboxanes (TXBs) using enzyme immunoassays. Oxidative stability was assessed by measuring thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) using colorimetric assays. Gene expression of antioxidant defense enzymes was determined by real time quantitative polymerase chain reaction (RT-qPCR). Rats fed KO had significantly lower DHA digestibility and brain DHA incorporation than SO and TO-fed rats. Of the n-3 PUFA sources, rats fed SO and TO had the highest n-3 PUFAs digestibility and in turn, tissue accretion. Higher tissue n-3 LC-PUFAs had no significant effect on 2-series PG and TXB metabolites. Despite higher tissue n-3 LC-PUFA deposition, there was no increase in oxidation susceptibility indicated by no significant increase in TBARS or decrease in TAC and gene expression of antioxidant defense enzymes, in SO or TO-fed rats. On the basis that the optimal n-3 PUFA sources should provide high digestibility and efficient tissue
Spatial and visual discrimination reversals in adult and geriatric rats exposed during gestation to methylmercury and n-3 polyunsaturated fatty acids

PubMed Central

Paletz, Elliott M.; Day, Jeremy J.; Craig-Schmidt, Margaret C.; Newland, M. Christopher

2007-01-01

Fish contain essential long chain polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), an omega-3 (or n-3) PUFA, but are also the main source of exposure to methylmercury (MeHg), a potent developmental neurotoxicant. Since n-3 PUFAs support neural development and function, benefits deriving from a diet rich in n-3s have been hypothesized to protect against deleterious effects of gestational MeHg exposure. To determine whether protection occurs at the behavioral level, female Long-Evans rats were exposed, in utero, to 0, 0.5, or 5 ppm of Hg as MeHg via drinking water, approximating exposures of 0, 40, and 400 μg Hg/kg/day and producing 0, 0.29, and 5.50 ppm of total Hg in the brains of siblings at birth. They also received pre- and postnatal exposure to one of two diets, both based on the AIN-93 semipurified formulation. A “fish-oil” diet was high in, and a “coconut-oil” diet was devoid of, DHA. Diets were approximately equal in α-linolenic acid and n-6 PUFAs. As adults, the rats were first assessed with a spatial discrimination reversal (SDR) procedure and later with a visual (nonspatial) discrimination reversal (VDR) procedure. MeHg increased the number of errors to criterion for both SDR and VDR during the first reversal, but effects were smaller or nonexistent on the original discrimination and on later reversals. No such MeHg-related deficits were seen when the rats were retested on SDR after two years of age. These results are consistent with previous reports and hypotheses that gestational MeHg exposure produces perseverative responding. No interactions between Diet and MeHg were found, suggesting that n-3 PUFAs do not guard against these behavioral effects. Brain Hg concentrations did not differ between the diets, either. In geriatric rats, failures to respond were less common and response latencies were shorter for rats fed the fish oil diet, suggesting that exposure to a diet rich in n-3s may lessen the impact of age
The Current Role of Omega-3 Fatty Acids in the Management of Atrial Fibrillation.

PubMed

Christou, Georgios A; Christou, Konstantinos A; Korantzopoulos, Panagiotis; Rizos, Evangelos C; Nikas, Dimitrios N; Goudevenos, John A

2015-09-22

The main dietary source of omega-3 polyunsaturated fatty acids (n-3 PUFA) is fish, which contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the present manuscript, we aimed to review the current evidence regarding the clinical role of n-3 PUFA in the prevention of atrial fibrillation (AF) and the possible underlying mechanisms. A literature search based on PubMed listings was performed using "Omega-3 fatty acids" and "atrial fibrilation" as key search terms. n-3 PUFA have been shown to attenuate structural atrial remodeling, prolong atrial effective refractory period through the prevention of reentry and suppress ectopic firing from pulmonary veins. Dietary fish intake has been found to have no effect on the incidence of AF in the majority of studies. Circulating DHA has been consistently reported to be inversely associated with AF risk, whereas EPA has no such effect. The majority of studies investigating the impact of n-3 PUFA supplementation on the incidence of AF following cardiac surgery reported no benefit, though most of them did not use n-3 PUFA pretreatment for adequate duration. Studies using adequate four-week pretreatment with n-3 PUFA before cardioversion of AF showed a reduction of the AF incidence. Although n-3 PUFA have antiarrhythmogenic properties, their clinical efficacy on the prevention of AF is not consistently supported. Further well-designed studies are needed to overcome the limitations of the existing studies and provide robust conclusions.
The Current Role of Omega-3 Fatty Acids in the Management of Atrial Fibrillation

PubMed Central

Christou, Georgios A.; Christou, Konstantinos A.; Korantzopoulos, Panagiotis; Rizos, Evangelos C.; Nikas, Dimitrios N.; Goudevenos, John A.

2015-01-01

Background: The main dietary source of omega-3 polyunsaturated fatty acids (n-3 PUFA) is fish, which contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the present manuscript, we aimed to review the current evidence regarding the clinical role of n-3 PUFA in the prevention of atrial fibrillation (AF) and the possible underlying mechanisms. Methods: A literature search based on PubMed listings was performed using “Omega-3 fatty acids” and “atrial fibrilation” as key search terms. Results: n-3 PUFA have been shown to attenuate structural atrial remodeling, prolong atrial effective refractory period through the prevention of reentry and suppress ectopic firing from pulmonary veins. Dietary fish intake has been found to have no effect on the incidence of AF in the majority of studies. Circulating DHA has been consistently reported to be inversely associated with AF risk, whereas EPA has no such effect. The majority of studies investigating the impact of n-3 PUFA supplementation on the incidence of AF following cardiac surgery reported no benefit, though most of them did not use n-3 PUFA pretreatment for adequate duration. Studies using adequate four-week pretreatment with n-3 PUFA before cardioversion of AF showed a reduction of the AF incidence. Conclusions: Although n-3 PUFA have antiarrhythmogenic properties, their clinical efficacy on the prevention of AF is not consistently supported. Further well-designed studies are needed to overcome the limitations of the existing studies and provide robust conclusions. PMID:26402674
Docosahexaneoic acid (22:6,n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26S proteasome-dependent pathways

PubMed Central

Botolin, Daniela; Wang, Yun; Christian, Barbara; Jump, Donald B.

2009-01-01

Insulin induces and dietary n-3 PUFAs suppress hepatic de novo lipogenesis by controlling sterol-regulatory element binding protein-1 nuclear abundance (nSREBP-1). Our goal was to define the mechanisms involved in this regulatory process. Insulin treatment of rat primary hepatocytes rapidly augments nSREBP-1 and mRNASREBP-1c while suppressing mRNAInsig-2 but not mRNAInsig-1. These events are preceded by rapid but transient increases in Akt and Erk phosphorylation. Removal of insulin from hepatocytes leads to a rapid decline in nSREBP-1 [half-time (T1/2) ~ 10 h] that is abrogated by inhibitors of 26S proteasomal degradation. 22:6,n-3, the major n-3 PUFA accumulating in livers of fish oil-fed rats, suppresses hepatocyte levels of nSREBP-1, mRNASREBP-1c, and mRNAInsig-2 but modestly and transiently induces mRNAInsig-1. More importantly, 22:6,n-3 accelerates the disappearance of hepatocyte nSREBP-1 (T1/2 ~ 4 h) through a 26S proteasome-dependent process. 22:6,n-3 has minimal effects on microsomal SREBP-1 and sterol-regulatory element binding protein cleavage-activating protein or nuclear SREBP-2. 22:6,n-3 transiently inhibits insulin-induced Akt phosphorylation but induces Erk phosphorylation. Inhibitors of Erk phosphorylation, but not overexpressed constitutively active Akt, rapidly attenuate 22:6,n-3 suppression of nSREBP-1. Thus, 22:6,n-3 suppresses hepatocyte nSREBP-1 through 26S proteasome- and Erk-dependent pathways. These studies reveal a novel mechanism for n-3 PUFA regulation of hepatocyte nSREBP-1 and lipid metabolism.—Botolin, D., Y. Wang, B. Christian, and D. B. Jump. Docosahexaneoic acid (22:6,n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26S proteasome-dependent pathways. PMID:16222032
Omega-3 dietary Fatty Acid status of healthy older adults in Tasmania, Australia: an observational study.

PubMed

Pittaway, J K; Chuang, L T; Ahuja, K D K; Beckett, J M; Glew, R H; Ball, M J

2015-05-01

To determine the dietary and supplement intake of omega-3 (n-3) polyunsaturated fatty acids (PUFA) of older Tasmanian adults; their plasma n-3 PUFA status and the relationship between n-3 PUFA intake and plasma status. Cross-sectional study. Launceston and surrounding regions, Tasmania, Australia. Seventy-three community-dwelling older adults: 23 men aged 70 ± 6.1 years and 50 women aged 70 ± 6.7 years. A validated, semi-quantitative food frequency questionnaire estimated dietary PUFA intake. The plasma phospholipid fraction of venous blood samples was analysed for fatty acid content. Anthropometric data was recorded. Thirty-five participants (48%) regularly ingested a fish oil supplement. Their plasma n-3 PUFA profile contained significantly more eicosapentaenoic acid (EPA) (odds ratio 3.14; 95% CI 1.37% to 7.30%; p<0.05) and docosahexaenoic acid (DHA) (odds ratio 2.64; 95% CI 1.16% to 6.01%; p<0.05) than non-supplement users. Fish and meat were the main dietary sources of n-3 PUFAs. Participants most commonly consumed fish 3-4 times per week. Significant associations of dietary α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA) and DHA with plasma n-3 PUFAs were noted but not always between dietary and plasma counterparts. Without the use of fish oil supplements, most study participants were unable to meet the recommended daily intake of 0.5g EPA and DHA combined; however, the plasma n-3 PUFA profile of non-supplement-users was still robust compared to other Australian and overseas studies.
Insulin-Sensitizing Effects of Omega-3 Fatty Acids: Lost in Translation?

PubMed Central

Lalia, Antigoni Z.; Lanza, Ian R.

2016-01-01

Omega-3 polyunsaturated fatty acids (n-3 PUFA) of marine origin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have been long studied for their therapeutic potential in the context of type 2 diabetes, insulin resistance, and glucose homeostasis. Glaring discordance between observations in animal and human studies precludes, to date, any practical application of n-3 PUFA as nutritional therapeutics against insulin resistance in humans. Our objective in this review is to summarize current knowledge and provide an up-to-date commentary on the therapeutic value of EPA and DHA supplementation for improving insulin sensitivity in humans. We also sought to discuss potential mechanisms of n-3 PUFA action in target tissues, in specific skeletal muscle, based on our recent work, as well as in liver and adipose tissue. We conducted a literature search to include all preclinical and clinical studies performed within the last two years and to comment on representative studies published earlier. Recent studies support a growing consensus that there are beneficial effects of n-3 PUFA on insulin sensitivity in rodents. Observational studies in humans are encouraging, however, the vast majority of human intervention studies fail to demonstrate the benefit of n-3 PUFA in type 2 diabetes or insulin-resistant non-diabetic people. Nevertheless, there are still several unanswered questions regarding the potential impact of n-3 PUFA on metabolic function in humans. PMID:27258299
Providing male rats deficient in iron and n-3 fatty acids with iron and alpha-linolenic acid alone affects brain serotonin and cognition differently from combined provision.

PubMed

Baumgartner, Jeannine; Smuts, Cornelius M; Zimmermann, Michael B

2014-06-13

We recently showed that a combined deficiency of iron (ID) and n-3 fatty acids (n-3 FAD) in rats disrupts brain monoamine metabolism and produces greater memory deficits than ID or n-3 FAD alone. Providing these double-deficient rats with either iron (Fe) or preformed docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) alone affected brain monoamine pathways differently from combined repletion and even exacerbated cognitive deficits associated with double-deficiency. Iron is a co-factor of the enzymes responsible for the conversion of alpha-linolenic acid (ALA) to EPA and DHA, thus, the provision of ALA with Fe might be more effective in restoring brain EPA and DHA and improving cognition in double-deficient rats than ALA alone. In this study we examined whether providing double-deficient rats with ALA and Fe, alone or in combination, can correct deficits in monoamine metabolism and cognition associated with double-deficiency. Using a 2 × 2 design, male rats with concurrent ID and n-3 FAD were fed an Fe + ALA, Fe + n-3 FAD, ID + ALA, or ID + n-3 FAD diet for 5 weeks (postnatal day 56-91). Biochemical measures, and spatial working and reference memory (using the Morris water maze) were compared to age-matched controls. In the hippocampus, we found a significant Fe × ALA interaction on DHA: Compared to the group receiving ALA alone, DHA was significantly higher in the Fe + ALA group. In the brain, we found significant antagonistic Fe × ALA interactions on serotonin concentrations. Provision of ALA alone impaired working memory compared with age-matched controls, while in the reference memory task ALA provided with Fe significantly improved performance. These results indicate that providing either iron or ALA alone to double-deficient rats affects serotonin pathways and cognitive performance differently from combined provision. This may be partly explained by the enhancing effect of Fe on the conversion of ALA to EPA and DHA.
Providing male rats deficient in iron and n-3 fatty acids with iron and alpha-linolenic acid alone affects brain serotonin and cognition differently from combined provision

PubMed Central

2014-01-01

Background We recently showed that a combined deficiency of iron (ID) and n-3 fatty acids (n-3 FAD) in rats disrupts brain monoamine metabolism and produces greater memory deficits than ID or n-3 FAD alone. Providing these double-deficient rats with either iron (Fe) or preformed docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) alone affected brain monoamine pathways differently from combined repletion and even exacerbated cognitive deficits associated with double-deficiency. Iron is a co-factor of the enzymes responsible for the conversion of alpha-linolenic acid (ALA) to EPA and DHA, thus, the provision of ALA with Fe might be more effective in restoring brain EPA and DHA and improving cognition in double-deficient rats than ALA alone. Methods In this study we examined whether providing double-deficient rats with ALA and Fe, alone or in combination, can correct deficits in monoamine metabolism and cognition associated with double-deficiency. Using a 2 × 2 design, male rats with concurrent ID and n-3 FAD were fed an Fe + ALA, Fe + n-3 FAD, ID + ALA, or ID + n-3 FAD diet for 5 weeks (postnatal day 56–91). Biochemical measures, and spatial working and reference memory (using the Morris water maze) were compared to age-matched controls. Results In the hippocampus, we found a significant Fe × ALA interaction on DHA: Compared to the group receiving ALA alone, DHA was significantly higher in the Fe + ALA group. In the brain, we found significant antagonistic Fe × ALA interactions on serotonin concentrations. Provision of ALA alone impaired working memory compared with age-matched controls, while in the reference memory task ALA provided with Fe significantly improved performance. Conclusion These results indicate that providing either iron or ALA alone to double-deficient rats affects serotonin pathways and cognitive performance differently from combined provision. This may be partly explained by the enhancing effect of Fe on
Influence of omega-3 fatty acids on skeletal muscle protein metabolism and mitochondrial bioenergetics in older adults.

PubMed

Lalia, Antigoni Z; Dasari, Surendra; Robinson, Matthew M; Abid, Hinnah; Morse, Dawn M; Klaus, Katherine A; Lanza, Ian R

2017-04-01

Omega-3 polyunsaturated fatty acids (n3-PUFA) are recognized for their anti-inflammatory effects and may be beneficial in the context of sarcopenia. We determined the influence of n3-PUFA on muscle mitochondrial physiology and protein metabolism in older adults. Twelve young (18-35 years) and older (65-85 years) men and women were studied at baseline. Older adults were studied again following n3-PUFA supplementation (3.9g/day, 16 weeks). Muscle biopsies were used to evaluate respiratory capacity (high resolution respirometry) and oxidant emissions (spectrofluorometry) in isolated mitochondria. Maximal respiration was significantly lower in older compared to young. n3-PUFA did not change respiration, but significantly reduced oxidant emissions. Participants performed a single bout of resistance exercise, followed by biopsies at 15 and 18 hours post exercise. Several genes involved in muscle protein turnover were significantly altered in older adults at baseline and following exercise, yet muscle protein synthesis was similar between age groups under both conditions. Following n3-PUFA supplementation, mixed muscle, mitochondrial, and sarcoplasmic protein synthesis rates were increased in older adults before exercise. n3-PUFA increased post-exercise mitochondrial and myofibrillar protein synthesis in older adults. These results demonstrate that n3-PUFA reduce mitochondrial oxidant emissions, increase postabsorptive muscle protein synthesis, and enhance anabolic responses to exercise in older adults.
Influence of omega-3 fatty acids on skeletal muscle protein metabolism and mitochondrial bioenergetics in older adults

PubMed Central

Lalia, Antigoni Z.; Dasari, Surendra; Robinson, Matthew M.; Abid, Hinnah; Morse, Dawn M.; Klaus, Katherine A.; Lanza, Ian R.

2017-01-01

Omega-3 polyunsaturated fatty acids (n3-PUFA) are recognized for their anti-inflammatory effects and may be beneficial in the context of sarcopenia. We determined the influence of n3-PUFA on muscle mitochondrial physiology and protein metabolism in older adults. Twelve young (18-35 years) and older (65-85 years) men and women were studied at baseline. Older adults were studied again following n3-PUFA supplementation (3.9g/day, 16 weeks). Muscle biopsies were used to evaluate respiratory capacity (high resolution respirometry) and oxidant emissions (spectrofluorometry) in isolated mitochondria. Maximal respiration was significantly lower in older compared to young. n3-PUFA did not change respiration, but significantly reduced oxidant emissions. Participants performed a single bout of resistance exercise, followed by biopsies at 15 and 18 hours post exercise. Several genes involved in muscle protein turnover were significantly altered in older adults at baseline and following exercise, yet muscle protein synthesis was similar between age groups under both conditions. Following n3-PUFA supplementation, mixed muscle, mitochondrial, and sarcoplasmic protein synthesis rates were increased in older adults before exercise. n3-PUFA increased post-exercise mitochondrial and myofibrillar protein synthesis in older adults. These results demonstrate that n3-PUFA reduce mitochondrial oxidant emissions, increase postabsorptive muscle protein synthesis, and enhance anabolic responses to exercise in older adults. PMID:28379838
In-Depth Study of the Interaction, Sensitivity, and Gating Modulation by PUFAs on K+ Channels; Interaction and New Targets

PubMed Central

Moreno, Cristina; de la Cruz, Alicia; Valenzuela, Carmen

2016-01-01

Voltage gated potassium channels (KV) are membrane proteins that allow selective flow of K+ ions in a voltage-dependent manner. These channels play an important role in several excitable cells as neurons, cardiomyocytes, and vascular smooth muscle. Over the last 20 years, it has been shown that omega-3 polyunsaturated fatty acids (PUFAs) enhance or decrease the activity of several cardiac KV channels. PUFAs-dependent modulation of potassium ion channels has been reported to be cardioprotective. However, the precise cellular mechanism underlying the cardiovascular benefits remained unclear in part because new PUFAs targets and signaling pathways continue being discovered. In this review, we will focus on recent data available concerning the following aspects of the KV channel modulation by PUFAs: (i) the exact residues involved in PUFAs-KV channels interaction; (ii) the structural PUFAs determinants important for their effects on KV channels; (iii) the mechanism of the gating modulation of KV channels and, finally, (iv) the PUFAs modulation of a few new targets present in smooth muscle cells (SMC), KCa1.1, K2P, and KATP channels, involved in vascular relaxation. PMID:27933000
Requirements of n-3 very long-chain PUFA in Atlantic salmon (Salmo salar L): effects of different dietary levels of EPA and DHA on fish performance and tissue composition and integrity.

PubMed

Bou, Marta; Berge, Gerd M; Baeverfjord, Grete; Sigholt, Trygve; Østbye, Tone-Kari; Romarheim, Odd Helge; Hatlen, Bjarne; Leeuwis, Robin; Venegas, Claudia; Ruyter, Bente

2017-01-01

Farmed salmon feeds have changed from purely marine-based diets with high levels of EPA and DHA in the 1990s to the current 70 % plant-based diets with low levels of these fatty acids (FA). The aim of this study was to establish the impacts of low dietary EPA and DHA levels on performance and tissue integrity of Atlantic salmon (Salmo salar). Atlantic salmon (50 g) in seawater were fed fourteen experimental diets, containing five levels (0, 0·5, 1·0, 1·5 and 2·0 %) of EPA, DHA or a 1:1 EPA+DHA plus control close to a commercial diet, to a final weight of 400 g. Lack of EPA and DHA did not influence mortality, but the n-3-deficient group exhibited moderately slower growth than those fed levels above 0·5 %. The heart and brain conserved EPA and DHA levels better than skeletal muscle, liver, skin and intestine. Decreased EPA and DHA favoured deposition of pro-inflammatory 20 : 4n-6 and 20 : 3n-6 FA in membrane phospholipids in all tissues. When DHA was excluded from diets, 18 : 3n-3 and EPA were to a large extent converted to DHA. Liver, skeletal and cardiac muscle morphology was normal in all groups, with the exception of cytoplasm packed with large or foamy vacuoles and sometimes swollen enterocytes of intestine in both deficient and EPA groups. DHA supplementation supported normal intestinal structure, and 2·0 % EPA+DHA alleviated deficiency symptoms. Thus, EPA and DHA dietary requirements cannot be based exclusively on growth; tissue integrity and fish health also need to be considered.
In ovo exposure to omega-3 fatty acids does not enhance omega-3 long-chain polyunsaturated fatty acid metabolism in broiler chickens.

PubMed

Kanakri, K; Carragher, J; Muhlhausler, B; Hughes, R; Gibson, R

2017-10-01

The content of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) in chicken meat can be boosted by feeding broilers a diet containing α-linolenic acid (ALA, from flaxseed oil), some of which is converted by hepatic enzymes to n-3 LCPUFA. However, most of the accumulated n-3 polyunsaturated fatty acid (PUFA) in meat tissues is still in the form of ALA. Despite this, the levels of chicken diets are being enhanced by the inclusion of vegetable and marine sources of omega-3 fats. This study investigated whether the capacity of chicken for n-3 LCPUFA accumulation could be enhanced or inhibited by exposure to an increased supply of ALA or n-3 LCPUFA in ovo. Breeder hens were fed either flaxseed oil (High-ALA), fish oil (high n-3 LCPUFA) or tallow- (low n-3 PUFA, Control) based diets. The newly hatched chicks in each group were fed either the High-ALA or the Control diets until harvest at 42 days' post-hatch. The n-3 PUFA content of egg yolk and day-old chick meat closely matched the n-3 PUFA composition of the maternal diet. In contrast, the n-3 PUFA composition of breast and leg meat tissues of the 42-day-old offspring closely matched the diet fed post-hatch, with no significant effect of maternal diet. Indeed, there was an inhibition of n-3 LCPUFA accumulation in meat of the broilers from the maternal Fish-Oil diet group when fed the post-hatch High-ALA diet. Therefore, this approach is not valid to elevate n-3 LCPUFA in chicken meat.
Altered erythrocyte membrane fatty acid profile in typical Rett syndrome: effects of omega-3 polyunsaturated fatty acid supplementation.

PubMed

Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia; Durand, Thierry; Galano, Jean-Marie; Cortelazzo, Alessio; Zollo, Gloria; Guerranti, Roberto; Gonnelli, Stefano; Caffarelli, Carla; Rossi, Marcello; Pecorelli, Alessandra; Valacchi, Giuseppe; Ciccoli, Lucia; Hayek, Joussef

2014-11-01

This study mainly aims at examining the erythrocyte membrane fatty acid (FAs) profile in Rett syndrome (RTT), a genetically determined neurodevelopmental disease. Early reports suggest a beneficial effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on disease severity in RTT. A total of 24 RTT patients were assigned to ω-3 PUFAs-containing fish oil for 12 months in a randomized controlled study (average DHA and EPA doses of 72.9, and 117.1mg/kgb.w./day, respectively). A distinctly altered FAs profile was detectable in RTT, with deficient ω-6 PUFAs, increased saturated FAs and reduced trans 20:4 FAs. FAs changes were found to be related to redox imbalance, subclinical inflammation, and decreased bone density. Supplementation with ω-3 PUFAs led to improved ω-6/ω-3 ratio and serum plasma lipid profile, decreased PUFAs peroxidation end-products, normalization of biochemical markers of inflammation, and reduction of bone hypodensity as compared to the untreated RTT group. Our data indicate that a significant FAs abnormality is detectable in the RTT erythrocyte membranes and is partially rescued by ω-3 PUFAs. Copyright © 2014 Elsevier Ltd. All rights reserved.
Supplementation with n-3, n-6, n-9 fatty acids in an insulin-resistance animal model: does it improve VLDL quality?

PubMed

Lucero, D; Olano, C; Bursztyn, M; Morales, C; Stranges, A; Friedman, S; Macri, E V; Schreier, L; Zago, V

2017-05-24

Insulin-resistance (IR), of increased cardiovascular risk, is characterized by the production of altered VLDL with greater atherogenicity. Dietary fatty acids influence the type of circulating VLDL. But, it is not clear how dietary fatty acids impact VLDL characteristics in IR. to evaluate the effects of n-3, n-6 and n-9 fatty acid supplementation on preventing atherogenic alterations in VLDL, in a diet-induced IR rat model. Male Wistar rats (180-200 g) were fed: standard diet (control, n = 8) and a sucrose rich diet (30% sucrose in water/12 weeks, SRD; n = 24). Simultaneously, SRD was subdivided into SRD-C (standard diet), and three other groups supplemented (15% w/w) with: fish oil (SRD-n3), sunflower oil (SRD-n6) and high oleic sunflower oil (SRD-n9). Lipid profile, free fatty acids, glucose, and insulin were measured. Isolated VLDL (d < 1.006 g ml -1 ) was characterized by chemical composition and size (size exclusion-HPLC). In comparison with SRD-C: SRD-n3 showed an improved lipoprotein profile (p < 0.01), with lower levels of insulin and HOMA-IR (p < 0.05). SRD-n6 showed increased levels of HDL-cholesterol and lower insulin levels. SRD-n9 did not exhibit differences in lipid and IR profile, and even favored weight gain and visceral fat. Only SRD-n3 prevented the alterations in VLDL-TG% (54.2 ± 4.4% vs. 68.6 ± 8.2, p < 0.05) and showed lower large VLDL-% (22.5[19.7-35.6] vs. 49.1[15.5-82.0], p < 0.05), while SRD-n6 and SRD-n9 did not show effects. In IR, while n-3 PUFA showed expected favorable effects, supplementation with n-6 PUFA and n-9 MUFA did not prevent atherogenic alterations of VLDL. Thus, the recommendations of supplementation with these fatty acids in general diet should be revised.

Influence of oilseed supplement ranging in n-6/n-3 ratio on fatty acid composition and Δ5-, Δ6-desaturase protein expression in steer muscles.

PubMed

Turner, T D; Mitchell, A; Duynisveld, J; Pickova, J; Doran, O; McNiven, M A

2012-12-01

This study investigated effects of roasted or extruded oilseed supplementation ranging in n-6/n-3 ratios from 0.3 to 5.0 on the fatty acid composition and expression of delta-5 desaturase (Δ5d) and Δ6-desaturase (Δ6d) protein in commercial steer cheek (m. masseter) and diaphragm (pars costalis diaphragmatis) muscles. In general, the n-6/n-3 ratio of the diet had a subsequent effect on the muscle n-6/n-3 ratio (P < 0.05), with muscle 18:2n-6 and 18:3n-3 content relating to proportion of dietary soya bean and linseed (P < 0.01). Compared with canola, pure linseed and soya bean diets reduced 14:1c-9 and 16:1c-9 (P < 0.05) but increased 18:1t-11 and c-9,t-11 conjugated linoleic acid (CLA) content (P < 0.01). Oilseed processing had a minor influence but extruded oilseeds increase 18:1t-11 and c-9,t-11 CLA compared with roasted (P < 0.05). Polar lipid 18:3n-3 and n-3 long-chain polyunsaturated fatty acid (LC, ⩾20 carbons PUFA) derivative content increased in relation to dietary linseed supplementation in the diaphragm (P < 0.01), whereas only 18:3n-3 was increased in the cheek (P < 0.01). Protein expression did not differ between diets; however, in each muscle the Δ5d protein expression had a stronger association with the desaturase products rather than the precursors. The relationship between Δ5d protein expression and the muscle LC n-6/n-3 ratio was negative in both muscles (P < 0.05). The relationship between Δ6d protein expression and the LC n-6/n-3 ratio was positive in the cheek (P < 0.001) and negative in the diaphragm (P < 0.05). In conclusion, diet n-6/n-3 ratio affected muscle 18:2n-6 and 18:3n-3 deposition, whereas the Δ5d and Δ6d protein expression had some influence on the polar lipid LC-PUFA profile. Results reaffirm that processed oilseeds can be used to increase the proportion of fatty acids potentially beneficial for human health, by influencing the formation of LC-PUFA and reducing the n-6/n-3 ratio.
Assessment of essential fatty acid and omega3-fatty acid status by measurement of erythrocyte 20:3omega9 (Mead acid), 22:5omega6/20:4omega6 and 22:5omega6/22:6omega3.

PubMed

Fokkema, M R; Smit, E N; Martini, I A; Woltil, H A; Boersma, E R; Muskiet, F A J

2002-11-01

Early suspicion of essential fatty acid deficiency (EFAD) or omega3-deficiency may rather focus on polyunsaturated fatty acid (PUFA) or long-chain PUFA (LCP) analyses than clinical symptoms. We determined cut-off values for biochemical EFAD, omega3-and omega3/22:6omega3 [docosahexaenoic acid (DHA)]-deficiency by measurement of erythrocyte 20:3omega9 (Mead acid), 22:5omega6/20:4omega6 and 22:5omega6/22:6omega3, respectively. Cut-off values, based on 97.5 percentiles, derived from an apparently healthy omnivorous group (six Dominica breast-fed newborns, 32 breast-fed and 27 formula+LCP-fed Dutch low-birth-weight infants, 31 Jerusalem infants, 33 Dutch 3.5-year-old infants, 69 omnivorous Dutch adults and seven Dominica mothers) and an apparently healthy group with low dietary LCP intake (81 formula-fed Dutch low-birth-weight infants, 12 Dutch vegans). Cut-off values were evaluated by their application in an EFAD suspected group of 108, mostly malnourished, Pakistani children, three pediatric patients with chronic fat-malabsorption (abetal-ipoproteinemia, congenital jejunal and biliary atresia) and one patient with a peroxisomal beta-oxidation disorder. Erythrocyte 20:3omega9, 22:5omega6/20:4omega6 and 22:5omega6/22:6omega3 proved age-dependent up to 0.2 years. Cut-off values for ages above 0.2 years were: 0.46mol% 20:3omega9 for EFAD, 0.068mol/mol 22:5omega6/20:4omega6 for omega3-deficiency, 0.22mol/mol 22:5omega6/22:6omega3 for omega3/DHA-marginality and 0.48mol/mol 22:5omega6/22:6omega3 for omega3/DHA-deficiency. Use of RBC 20:3omega9 and 22:5omega6/20:4omega6 cut-off values identified 20.4% of the Pakistani subjects as EFAD+omega3-deficient, 12.9% as EFAD+omega3-sufficient, 38.9% as EFA-sufficient+omega3-deficient and 27.8% as EFA-sufficient+omega3-sufficient. The patient with the peroxisomal disorder was classified as EFA-sufficient, omega3-sufficient (based on RBC 22:5omega6/20:4omega6) and omega3/DHA-deficient (based on RBC 22:5omega6/22:6omega3). The three
Marine n-3 polyunsaturated fatty acids in patients with end-stage renal failure and in subjects without kidney disease: a comparative study.

PubMed

Madsen, Trine; Christensen, Jeppe H; Svensson, My; Witt, Petra M; Toft, Egon; Schmidt, Erik B

2011-03-01

Patients with end-stage renal disease treated with chronic hemodialysis (HD) are reported to have low levels of marine n-3 polyunsaturated fatty acids (PUFA) in plasma and cell membranes compared with healthy subjects. The aim of this study was to investigate whether n-3 PUFA levels in plasma and cells are lower in HD patients as compared with subjects without kidney disease. A comparative study was carried out. This study was carried out at the Departments of Nephrology and Cardiology, Aalborg Hospital, Aarhus University Hospital, Denmark. This study consisted of 2 study populations comprising HD patients and 5 study populations comprising subjects without kidney disease. The fatty acid distribution in plasma phospholipids and platelet phospholipids was measured using gas chromatography. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) levels in plasma or serum phospholipids and platelet phospholipids in HD patients were compared with n-3 PUFA levels in subjects without kidney disease. EPA and DHA were lower and AA/EPA was higher in plasma/serum phospholipids in HD patients than in subjects without kidney disease. Similarly, higher AA and AA/EPA and lower EPA and DHA levels were found in platelet phospholipids of HD patients. Adjustment for gender, age, and habitual intake of fish and fish oil supplements did not change these results. HD patients have lower n-3 PUFA levels in plasma and cells compared with subjects without kidney disease. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
A systematic review and meta-analysis of the n-3 polyunsaturated fatty acids effects on inflammatory markers in colorectal cancer.

PubMed

Mocellin, Michel C; Camargo, Carolina Q; Nunes, Everson Araujo; Fiates, Giovanna M R; Trindade, Erasmo B S M

2016-04-01

Cancer and inflammation are closely related and an exacerbated inflammatory process can lead to tumor progression and a worse prognosis for the patient with cancer. Scientific literature has shown evidence that n-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory action, and for this reason could be useful as an adjuvant in the treatment of some cancers. A systematic review and meta-analysis of the literature was conducted until September, 2014, to evaluate the effects of n-3 PUFA on inflammatory mediators in colorectal cancer (CRC) patients. Clinical trials were systematically searched in three electronic databases and screening reference lists. Random meta-analysis model was used to calculate the overall and stratified effect sizes. Nine trials, representing 475 patients with CRC, evaluated effects of n-3 PUFA on cytokines (n = 6) and/or acute phase proteins (n = 5) levels. n-3 PUFA reduce the levels of IL-6 (SMD -2.34; 95% CI -4.37, -0.31; p = 0.024) and increase albumin (SMD 0.31; 95% CI 0.06, 0.56; p = 0.014) in overall analyses. In stratified analyses, reduction in IL-6 levels occurs in surgical patients that received 0.2 g/kg of fish oil parenterally at postoperative period (SMD -0.65; 95% CI -1.06, -0.24; p = 0.002), while, increase in albumin concentration occurs in surgical patients that received ≥ 2.5 g/d of EPA + DHA orally at preoperative period (SMD 0.34; 95% CI 0.02, 0.66; p = 0.038). In patients undergoing chemotherapy, the supplementation of 0.6 g/d of EPA + DHA during 9 week reduces CRP levels (SMD -0.95; 95% CI -1.73, -0.17; p = 0.017), and CRP/albumin ratio (SMD -0.95; 95% CI -1.73, -0.18; p = 0.016). The results suggest benefits on some inflammatory mediators with the use of n-3 PUFA on CRC patients, but these benefits are specific to certain supplementation protocols involving duration, dose and route of administration, and also, the concomitant anti-cancer treatment adopted. Copyright © 2015 Elsevier Ltd and
Co-Enzyme Q10 and n-3 Polyunsaturated Fatty Acid Supplementation Reverse Intermittent Hypoxia-Induced Growth Restriction and Improved Antioxidant Profiles in Neonatal Rats

PubMed Central

Cai, Charles L.; Henry, Michael M.; Chowdhury, Sara; Valencia, Gloria B.; Aranda, Jacob V.

2017-01-01

Neonatal intermittent hypoxia (IH) increases the risk for many morbidities in extremely low birth weight/gestational age (ELBW/ELGA) neonates with compromised antioxidant systems and poor growth. We hypothesized that supplementation with coenzyme Q10 (CoQ10, ubiquinol) or n-3 polyunsaturated fatty acids (PUFAs) during neonatal IH improves antioxidant profiles and somatic growth in neonatal rats. Newborn rats were exposed to two IH paradigms at birth (P0): (1) 50% O2 with brief hypoxic episodes (12% O2); or (2) room air (RA) with brief hypoxia, until P14 during which they received daily oral CoQ10 in olive oil, n-3 PUFAs in fish oil, or olive oil only from P0 to P14. Pups were studied at P14 or placed in RA until P21 for recovery from IH (IHR). Body weight and length; organ weights; and serum antioxidants and growth factors were determined at P14 and P21. Neonatal IH resulted in sustained reductions in somatic growth, an effect that was reversed with n-3 PUFAs. Improved growth was associated with higher serum growth factors. CoQ10 decreased superoxide dismutase (SOD) and glutathione, but increased catalase, suggesting reduced oxidative stress. Further studies are needed to determine the synergistic effects of CoQ10 and n-3 PUFA co-administration for the prevention of IH-induced oxidative stress and postnatal growth deficits. PMID:29258174
Different sources of omega-3 polyunsaturated fatty acids affects apparent digestibility, tissue deposition, and tissue oxidative stability in growing female rats

PubMed Central

2011-01-01

Background Numerous health benefits associated with increased omega-3 polyunsaturated fatty acid (n-3 PUFA) consumption has lead to an increasing variety of available n-3 PUFA sources. However, sources differ in the type, amount, and structural form of the n-3 PUFAs. Therefore, the objective of this study was to determine the effect of different sources of ω-3 PUFAs on digestibility, tissue deposition, eicosanoid metabolism, and oxidative stability. Methods Female Sprague-Dawley rats (age 28 d) were randomly assigned (n = 10/group) to be fed a high fat 12% (wt) diet consisting of either corn oil (CO) or n-3 PUFA rich flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) oil for 8 weeks. Rats were individually housed in metabolic cages to determine fatty acid digestibility. Diet and tissue fatty acid composition was analyzed by gas chromatography and lipid classes using thin layer chromatography. Eicosanoid metabolism was determined by measuring urinary metabolites of 2-series prostaglandins (PGs) and thromoboxanes (TXBs) using enzyme immunoassays. Oxidative stability was assessed by measuring thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) using colorimetric assays. Gene expression of antioxidant defense enzymes was determined by real time quantitative polymerase chain reaction (RT-qPCR). Results Rats fed KO had significantly lower DHA digestibility and brain DHA incorporation than SO and TO-fed rats. Of the n-3 PUFA sources, rats fed SO and TO had the highest n-3 PUFAs digestibility and in turn, tissue accretion. Higher tissue n-3 LC-PUFAs had no significant effect on 2-series PG and TXB metabolites. Despite higher tissue n-3 LC-PUFA deposition, there was no increase in oxidation susceptibility indicated by no significant increase in TBARS or decrease in TAC and gene expression of antioxidant defense enzymes, in SO or TO-fed rats. Conclusions On the basis that the optimal n-3 PUFA sources should provide high
Intake levels of dietary long-chain PUFAs modify the association between genetic variation in FADS and LDL-C.

PubMed

Hellstrand, S; Sonestedt, E; Ericson, U; Gullberg, B; Wirfält, E; Hedblad, B; Orho-Melander, M

2012-06-01

Polymorphisms of the FA desaturase (FADS) gene cluster have been associated with LDL, HDL, and triglyceride concentrations. Because FADS converts α-linolenic acid (ALA) and linoleic acid into PUFAs, we investigated the interaction between different PUFA intakes and the FADS polymorphism rs174547 (T>C) on fasting blood lipid and lipoprotein concentrations. We included 4,635 individuals (60% females, 45-68 years) from the Swedish population-based Malmö Diet and Cancer cohort. Dietary intakes were assessed by a modified diet history method including 7-day registration of cooked meals. The C-allele of rs174547 was associated with lower LDL concentration (P = 0.03). We observed significant interaction between rs174547 and long-chain ω-3 PUFA intakes on LDL (P = 0.01); the C-allele was only associated with lower LDL among individuals in the lowest tertile of long-chain ω-3 PUFA intakes (P < 0.001). In addition, significant interaction was observed between rs174547 and the ratio of ALA and linoleic FA intakes on HDL (P = 0.03). However, no significant associations between the C-allele and HDL were detected within the intake tertiles of the ratio. Our findings suggest that dietary intake levels of different PUFAs modify the associated effect of genetic variation in FADS on LDL and HDL.
The distinct spectra of tumor-associated Apc mutations in mismatch repair-deficient Apc1638N mice define the roles of MSH3 and MSH6 in DNA repair and intestinal tumorigenesis.

PubMed

Kuraguchi, M; Yang, K; Wong, E; Avdievich, E; Fan, K; Kolodner, R D; Lipkin, M; Brown, A M; Kucherlapati, R; Edelmann, W

2001-11-01

In mammalian cells, mismatch recognition has been attributed to two partially redundant heterodimeric protein complexes of MutS homologues, MSH2-MSH3 and MSH2-MSH6. We have conducted a comparative analysis of Msh3 and Msh6 deficiency in mouse intestinal tumorigenesis by generating Apc1638N mice deficient in Msh3, Msh6 or both. We have found that Apc1638N mice defective in Msh6 show reduced survival and a 6-7-fold increase in intestinal tumor multiplicity. In contrast, Msh3-deficient Apc1638N mice showed no difference in survival and intestinal tumor multiplicity as compared with Apc1638N mice. However, when Msh3 deficiency is combined with Msh6 deficiency (Msh3(-/-)Msh6(-/-)Apc1638N), the survival rate of the mice was further reduced compared to Msh6(-/-)Apc(1638N) mice because of a high multiplicity of intestinal tumors at a younger age. Almost 90% of the intestinal tumors from both Msh6(-/-)Apc1638N and Msh3(-/-)Msh6(-/-)Apc1638N mice contained truncation mutations in the wild-type Apc allele. Apc mutations in Msh6(-/-)Apc1638N mice consisted predominantly of base substitutions (93%) creating stop codons, consistent with a major role for Msh6 in the repair of base-base mismatches. However, in Msh3(-/-)Msh6(-/-)Apc1638N tumors, we observed a mixture of base substitutions (46%) and frameshifts (54%), indicating that in Msh6(-/-)Apc1638N mice frameshift mutations in the Apc gene were suppressed by Msh3. Interestingly, all except one of the Apc mutations detected in mismatch repair-deficient intestinal tumors were located upstream of the third 20-amino acid beta-catenin binding repeat and before all of the Ser-Ala-Met-Pro repeats, suggesting that there is selection for loss of multiple domains involved in beta-catenin regulation. Our analysis therefore has revealed distinct mutational spectra and clarified the roles of Msh3 and Msh6 in DNA repair and intestinal tumorigenesis.
A diet with 3% of energy from a mixture of Omega-3 fatty acids significantly increases in vivo lipid peroxidation in postmenopausal women

USDA-ARS?s Scientific Manuscript database

Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA) are recommended by public health organizations to reduce the risk of disease. However, n-3 PUFA are susceptible to an increase in lipid peroxidation in the human body. As part of a crossover dietary intervention study of a diet (20% of energy ...
The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter

USDA-ARS?s Scientific Manuscript database

Scope: Omega-3 PUFAs (n-3 PUFAs) reduce IL-6 gene expression, but their effects on transcription regulatory mechanisms are unknown. We aimed to conduct an integrated analysis with both population and in vitro studies to systematically explore the relationships among n-3 PUFA, DNA methylation, single...
Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study

PubMed Central

Bélanger, Stacey Ageranioti; Vanasse, Michel; Spahis, Schohraya; Sylvestre, Marie-Pierre; Lippé, Sarah; l’Heureux, François; Ghadirian, Parviz; Vanasse, Catherine-Marie; Levy, Emile

2009-01-01

BACKGROUND: Although several clinical trials have evaluated the impact of n-3 polyunsaturated fatty acid (PUFA) on patients with attention-deficit hyperactivity disorder (ADHD), changes in plasma PUFA composition were not always assessed following n-3 supplementation. Furthermore, no reports are available on the efficacy of n-3 PUFA in Canadian youth with ADHD. OBJECTIVES: To determine fatty acid (FA) composition, and the efficacy and safety of n-3 PUFA supplementation on ADHD clinical symptoms in French Canadian primary school children. PATIENTS AND METHODS: The Strengths and Weaknesses in ADHD and Normal Behaviors (SWAN) and Conners’ questionnaires were used to assess changes in ADHD symptoms in 37 children (only 26 children completed the study from zero to 16 weeks). They were divided into two groups (A and B), and participated in a 16-week, double-blind, one-way, crossover randomized study. In the first phase, group A received the n-3 PUFA supplement and group B received n-6 PUFA (sunflower oil) as a placebo. During the second phase, group B received the active n-3 PUFA supplement that was continued in group A. FA composition and lipid profile were assessed during the phases of the study. RESULTS: FA differences between groups were observed in the 26 patients. Supplementation with n-3 PUFA resulted in significant increases in eicosapentaenoic and docosahexaenoic acids in group A, while group B was enriched with alpha-linolenic, gamma-linolenic and homo-gamma-linolenic acids. The n-3 PUFA supplement was tolerated without any adverse effects. A statistically significant improvement in symptoms was noted based on the parent version of the Conners’ questionnaire from baseline to the end of phase 1, and this amelioration continued from phases 1 to 2, although the latter changes from phases 1 and 2 were not statistically significant in any of the subscales except for the subscale measuring inattention in group B. The improvement was greater in patients from group
A meta-analysis of n-3 polyunsaturated fatty acids effects on circulating acute-phase protein and cytokines in gastric cancer.

PubMed

Mocellin, Michel C; Fernandes, Ricardo; Chagas, Thayz R; Trindade, Erasmo B S M

2018-06-01

Chronic inflammation is related with cancer and leads to worsening prognosis in cancer patients. n-3 polyunsaturated fatty acids (PUFAs) supplementation has been proposed as adjuvant treatment in cancer due anti-inflammatory properties. In the present meta-analysis, we pooled randomized clinical trials (RCTs) assessing the effects of n-3 PUFAs (from fish oil isolated or added in an immunonutrition formula) on inflammatory markers in gastric cancer. A comprehensive literature search was performed in Medline, Scopus, Cochrane library, Science Direct and Web of Science, besides GOOGLE Scholar and a hand searching of reference lists, through July 2016. We pooled the effect size from individual studies using a random-effect model and carried out heterogeneity and sensitivity analyses. Nine trials (698 patients) fulfilled the entry criteria and were included in the synthesis of the systematic review. Eight were carried out in surgical patients and one in patients that received chemotherapy. Four used only fish oil as intervention and five used an immunonutrition formula. Global meta-analysis demonstrated higher albumin (7 studies, SMD 0.28; 95% CI 0.07, 0.48) and prealbumin (4 studies, SMD 0.56; 95% CI 0.12, 1.00) concentrations, and lower IL-6 (2 studies, SMD -0.71; 95% CI -1.15, -0.27) and TNF-α (2 studies, SMD -0.92; 95% CI -1.58, -0.26) concentrations in patients of the intervention group as compared to control group. However, total protein, transferrin and CRP concentrations were not improved by n-3 PUFAs supplementation. This study provides evidence that n-3 PUFAs supplementation from fish oil or added an immunonutrition formula has favorable effects on inflammatory markers in gastric cancer patients undergoing surgical procedures. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
The effect of different cooking methods on fatty acid composition and antioxidant activity of n-3 fatty acids fortified tilapia meat with or without clove essential oil.

PubMed

Ramezani-Fard, Ehsan; Romano, Nicholas; Goh, Yong-Meng; Oskoueian, Ehsan; Ehteshami, Fariborz; Ebrahimi, Mahdi

2016-07-01

Tilapia farmers are increasingly relying on dietary fish oil alternatives which substantially reduces health beneficial n-3 polyunsaturated fatty acids (PUFA) in tilapia products.? This may be further exacerbated depending on the cooking method.? This study aimed to evaluate the effects of different cooking methods on the fatty acid composition and oxidative stability of tilapia minced meat after prior fish oil fortifications with or without clove essential oil. Results showed that frying tilapia in either sunflower or palm oil significantly increased the saturated fatty acid and linoleic acid content, respectively, of tilapia. However, fish oil fortifications significantly increased the n-3 PUFA content, but tended to decrease oxidative stability, particularly when microwaving. This was mitigated by clove essential oil, which significantly improved oxidative stability after cooking. Results indicate that n-3 PUFA and clove essential oil fortifications is an effective method to deliver and protect these beneficial fatty acids for human consumers. ?
Effects of omega-3 fatty acid supplementation on the pattern of oxylipins: a short review about the modulation of hydroxy-, dihydroxy-, and epoxy-fatty acids.

PubMed

Ostermann, Annika I; Schebb, Nils Helge

2017-07-19

A growing body of evidence suggests that the intake of the long chain omega-3 polyunsaturated fatty acids (n3-PUFA) eicosapentaenoic acid (C20:5 n3, EPA) and docosahexaenoic acid (C22:6 n3, DHA) is linked to beneficial health effects, particularly in the prevention of cardiovascular and inflammatory diseases. Although the molecular mode of action of n3-PUFA is still not fully understood, it is not controversial that a significant portion of the (patho)-physiological effects of PUFA are mediated by their oxidative metabolites, i.e. eicosanoids and other oxylipins. Quantitative targeted oxylipin methods allow the comprehensive monitoring of n3-PUFA supplementation induced changes in the pattern of oxylipins in order to understand their biology. In this short review, results from intervention studies are summarized analyzing >30 oxylipins from different PUFAs in response to n3-PUFA supplementation. The results are not only qualitatively compared with respect to the study design, n3-PUFA dose and trends in the lipid mediators, but also quantitatively based on the relative change in the oxylipin level induced by n3-PUFA. The evaluation of the data from the studies shows that the change in oxylipins generally corresponded to the observed changes in their precursor PUFA, i.e. the lower the individual n3-status at the baseline, the higher the increase in EPA and DHA derived oxylipins. The strongest relative increases were found for EPA derived oxylipins, while changes in arachidonic acid (C20:4 n6, ARA) derived eicosanoids were heterogeneous. After 3-12 weeks of supplementation, similar relative changes were observed in free and total (free + esterified) oxylipins in plasma and serum. Regarding EPA derived oxylipins, the results indicate a trend for a linear increase with dose. However, the interpretation of the quantitative oxylipin patterns between studies is hampered by strong inter-individual variances in oxylipin levels between and also within the studies. In the
Maternal dietary omega-3 fatty acid supplementation reduces placental oxidative stress and increases fetal and placental growth in the rat.

PubMed

Jones, Megan L; Mark, Peter J; Mori, Trevor A; Keelan, Jeffrey A; Waddell, Brendan J

2013-02-01

Placental oxidative stress plays a key role in the pathophysiology of several placenta-related disorders including intrauterine growth restriction. Oxidative stress occurs when accumulation of reactive oxygen species damages DNA, proteins, and lipids, an outcome normally limited by antioxidant defenses. Dietary supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) may limit oxidative stress by increasing antioxidant capacity, but n-3 PUFAs are also highly susceptible to lipid peroxidation; so n-3 PUFA supplementation is potentially harmful. Here we examined the effect of n-3 PUFAs on placental oxidative stress and on placental and fetal growth in the rat. We also investigated whether diet-induced changes in maternal plasma fatty acid profiles are associated with comparable changes in placental and fetal tissues. Rats were fed either standard or high n-3 PUFA diets from Day 1 of pregnancy, and tissues were collected on Day 17 or 22 (term = Day 23). Dietary supplementation with n-3 PUFAs increased fetal (6%) and placental (12%) weights at Day 22, the latter attributable primarily to growth of the labyrinth zone (LZ). Increased LZ weight was accompanied by reduced LZ F(2)-isoprostanes (by 31% and 11% at Days 17 and 22, respectively), a marker of oxidative damage. Maternal plasma PUFA profiles were altered by dietary fatty acid intake and were strongly predictive of corresponding profiles in placental and fetal tissues. Our data indicate that n-3 PUFA supplementation reduces placental oxidative stress and enhances placental and fetal growth. Moreover, fatty acid profiles in the mother, placenta, and fetus are highly dependent on dietary fatty acid intake.
Physiological and glycomic characterization of N-acetylglucosaminyltransferase-IVa and -IVb double deficient mice

PubMed Central

Takamatsu, Shinji; Antonopoulos, Aristotelis; Ohtsubo, Kazuaki; Ditto, David; Chiba, Yasunori; Le, Dzung T.; Morris, Howard R.; Haslam, Stuart M.; Dell, Anne; Marth, Jamey D.; Taniguchi, Naoyuki

2010-01-01

N-Acetylglucosaminyltransferase-IV (GnT-IV) has two isoenzymes, GnT-IVa and GnT-IVb, which initiate the GlcNAcβ1-4 branch synthesis on the Manα1-3 arm of the N-glycan core thereby increasing N-glycan branch complexity and conferring endogenous lectin binding epitopes. To elucidate the physiological significance of GnT-IV, we engineered and characterized GnT-IVb-deficient mice and further generated GnT-IVa/-IVb double deficient mice. In wild-type mice, GnT-IVa expression is restricted to gastrointestinal tissues, whereas GnT-IVb is broadly expressed among organs. GnT-IVb deficiency induced aberrant GnT-IVa expression corresponding to the GnT-IVb distribution pattern that might be attributed to increased Ets-1, which conceivably activates the Mgat4a promoter, and thereafter preserved apparent GnT-IV activity. The compensative GnT-IVa expression might contribute to amelioration of the GnT-IVb-deficient phenotype. GnT-IVb deficiency showed mild phenotypic alterations in hematopoietic cell populations and hemostasis. GnT-IVa/-IVb double deficiency completely abolished GnT-IV activity that resulted in the disappearance of the GlcNAcβ1-4 branch on the Manα1-3 arm that was confirmed by MALDI-TOF MS and GC-MS linkage analyses. Comprehensive glycomic analyses revealed that the abundance of terminal moieties was preserved in GnT-IVa/-IVb double deficiency that was due to the elevated expression of glycosyltransferases regarding synthesis of terminal moieties. Thereby, this may maintain the expression of glycan ligands for endogenous lectins and prevent cellular dysfunctions. The fact that the phenotype of GnT-IVa/-IVb double deficiency largely overlapped that of GnT-IVa single deficiency can be attributed to the induced glycomic compensation. This is the first report that mammalian organs have highly organized glycomic compensation systems to preserve N-glycan branch complexity. PMID:20015870
Differences in the intramolecular structure of structured oils do not affect pancreatic lipase activity in vitro or the absorption by rats of (n-3) fatty acids.

PubMed

Porsgaard, Trine; Xu, Xuebing; Göttsche, Jesper; Mu, Huiling

2005-07-01

The fatty acid composition and intramolecular structure of dietary triacylglycerols (TAGs) influence their absorption. We compared the in vitro pancreatic lipase activity and the lymphatic transport in rats of fish oil and 2 enzymatically interesterified oils containing 10:0 and (n-3) PUFAs of marine origin to investigate whether the positional distribution of fatty acids influenced the overall bioavailability of (n-3) PUFAs in the body. The structured oils had the (n-3) PUFA either mainly at the sn-1,3 position (LML, M = medium-chain fatty acid, L = long-chain fatty acid) or mainly at the sn-2 position (MLM). Oils were administered to lymph-cannulated rats and lymph was collected for 24 h. The fatty acid composition as well as the lipid class distribution of lymph samples was determined. In vitro pancreatic lipase activity was greater when fish oil was the substrate than when the structured oils were the substrates (P < 0.001 at 40 min). This was consistent with a greater 8-h recovery of total fatty acids from fish oil compared with the 2 structured oils (P < 0.05). The absorption profiles of MLM and LML in rats and their in vitro rates of lipase activity did not differ. This indicates that the absorption rate is highly influenced by the lipase activity, which in turn is affected by the fatty acid composition and intramolecular structure. The lipid class distribution in lymph collected from the 3 groups of rats did not differ. In conclusion, the intramolecular structure did not affect the overall absorption of (n-3) PUFAs.
Anthocyanins do not influence long-chain n-3 fatty acid status: studies in cells, rodents and humans.

PubMed

Vauzour, David; Tejera, Noemi; O'Neill, Colette; Booz, Valeria; Jude, Baptiste; Wolf, Insa M A; Rigby, Neil; Silvan, Jose Manuel; Curtis, Peter J; Cassidy, Aedin; de Pascual-Teresa, Sonia; Rimbach, Gerald; Minihane, Anne Marie

2015-03-01

Increased tissue status of the long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) is associated with cardiovascular and cognitive benefits. Limited epidemiological and animal data suggest that flavonoids, and specifically anthocyanins, may increase EPA and DHA levels, potentially by increasing their synthesis from the shorter-chain n-3 PUFA, α-linolenic acid. Using complimentary cell, rodent and human studies we investigated the impact of anthocyanins and anthocyanin-rich foods/extracts on plasma and tissue EPA and DHA levels and on the expression of fatty acid desaturase 2 (FADS2), which represents the rate limiting enzymes in EPA and DHA synthesis. In experiment 1, rats were fed a standard diet containing either palm oil or rapeseed oil supplemented with pure anthocyanins for 8 weeks. Retrospective fatty acid analysis was conducted on plasma samples collected from a human randomized controlled trial where participants consumed an elderberry extract for 12 weeks (experiment 2). HepG2 cells were cultured with α-linolenic acid with or without select anthocyanins and their in vivo metabolites for 24 h and 48 h (experiment 3). The fatty acid composition of the cell membranes, plasma and liver tissues were analyzed by gas chromatography. Anthocyanins and anthocyanin-rich food intake had no significant impact on EPA or DHA status or FADS2 gene expression in any model system. These data indicate little impact of dietary anthocyanins on n-3 PUFA distribution and suggest that the increasingly recognized benefits of anthocyanins are unlikely to be the result of a beneficial impact on tissue fatty acid status. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Anthocyanins do not influence long-chain n-3 fatty acid status: studies in cells, rodents and humans☆

PubMed Central

Vauzour, David; Tejera, Noemi; O'Neill, Colette; Booz, Valeria; Jude, Baptiste; Wolf, Insa M.A.; Rigby, Neil; Silvan, Jose Manuel; Curtis, Peter J.; Cassidy, Aedin; de Pascual-Teresa, Sonia; Rimbach, Gerald; Minihane, Anne Marie

2015-01-01

Increased tissue status of the long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) is associated with cardiovascular and cognitive benefits. Limited epidemiological and animal data suggest that flavonoids, and specifically anthocyanins, may increase EPA and DHA levels, potentially by increasing their synthesis from the shorter-chain n-3 PUFA, α-linolenic acid. Using complimentary cell, rodent and human studies we investigated the impact of anthocyanins and anthocyanin-rich foods/extracts on plasma and tissue EPA and DHA levels and on the expression of fatty acid desaturase 2 (FADS2), which represents the rate limiting enzymes in EPA and DHA synthesis. In experiment 1, rats were fed a standard diet containing either palm oil or rapeseed oil supplemented with pure anthocyanins for 8 weeks. Retrospective fatty acid analysis was conducted on plasma samples collected from a human randomized controlled trial where participants consumed an elderberry extract for 12 weeks (experiment 2). HepG2 cells were cultured with α-linolenic acid with or without select anthocyanins and their in vivo metabolites for 24 h and 48 h (experiment 3). The fatty acid composition of the cell membranes, plasma and liver tissues were analyzed by gas chromatography. Anthocyanins and anthocyanin-rich food intake had no significant impact on EPA or DHA status or FADS2 gene expression in any model system. These data indicate little impact of dietary anthocyanins on n-3 PUFA distribution and suggest that the increasingly recognized benefits of anthocyanins are unlikely to be the result of a beneficial impact on tissue fatty acid status. PMID:25573539
Enriched Endogenous Omega-3 Polyunsaturated Fatty Acids Protect Cortical Neurons from Experimental Ischemic Injury.

PubMed

Shi, Zhe; Ren, Huixia; Luo, Chuanming; Yao, Xiaoli; Li, Peng; He, Chengwei; Kang, Jing-X; Wan, Jian-Bo; Yuan, Ti-Fei; Su, Huanxing

2016-11-01

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential in a variety of neurological disorders, including ischemic stroke. However, the underlying mechanisms still lack investigation. Here, we report that cultured cortical neurons isolated from fat-1 mice with high endogenous n-3 PUFAs were tolerant to oxygen-glucose deprivation/reperfusion (OGD/R) injury. Fat-1 neurons exhibited significantly attenuated reactive oxygen species (ROS) activation induced by OGD/R injury, upregulated antiapoptotic proteins Bcl-2 and Bcl-xL, and reduced cleaved caspase-3. Exogenous administration of docosahexaenoic acid (DHA), a major component of the n-3 PUFA family, resulted in similar protective effects on cultured cortex neurons. We further verified the protective effects of n-3 PUFAs in vivo, using a mini ischemic model with a reproducible cortical infarct and manifest function deficits by occlusion of the distal branch of the middle cerebral artery with focused femtosecond laser pulses. The Fat-1 animals showed decreased ROS expression and higher level of glutathione in the injured brain, associated with improved functional recovery. We therefore provide evidence that n-3 PUFAs exert their protective effects against ischemic injury both in vitro and in vivo, partly through inhibiting ROS activation.

The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter

PubMed Central

Ma, Yiyi; Smith, Caren E.; Lai, Chao-Qiang; Irvin, Marguerite R.; Parnell, Laurence D.; Lee, Yu-Chi; Pham, Lucia D.; Aslibekyan, Stella; Claas, Steven A.; Tsai, Michael Y.; Borecki, Ingrid B.; Kabagambe, Edmond K.; Ordovás, José M.; Absher, Devin M.; Arnett, Donna K.

2016-01-01

Scope Omega-3 PUFAs (n-3 PUFAs) reduce IL-6 gene expression, but their effects on transcription regulatory mechanisms are unknown. We aimed to conduct an integrated analysis with both population and in vitro studies to systematically explore the relationships among n-3 PUFA, DNA methylation, single nucleotide polymorphisms (SNPs), gene expression, and protein concentration of IL6. Methods and results Using data in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study and the Encyclopedia of DNA Elements (ENCODE) consortium, we found that higher methylation of IL6 promoter cg01770232 was associated with higher IL-6 plasma concentration (p = 0.03) and greater IL6 gene expression (p = 0.0005). Higher circulating total n-3 PUFA was associated with lower cg01770232 methylation (p = 0.007) and lower IL-6 concentration (p = 0.02). Moreover, an allele of IL6 rs2961298 was associated with higher cg01770232 methylation (p = 2.55 × 10−7). The association between n-3 PUFA and cg01770232 methylation was dependent on rs2961298 genotype (p = 0.02), but higher total n-3 PUFA was associated with lower cg01770232 methylation in the heterozygotes (p = 0.04) not in the homozygotes. Conclusion Higher n-3 PUFA is associated with lower methylation at IL6 promoter, which may be modified by IL6 SNPs. PMID:26518637
The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter.

PubMed

Ma, Yiyi; Smith, Caren E; Lai, Chao-Qiang; Irvin, Marguerite R; Parnell, Laurence D; Lee, Yu-Chi; Pham, Lucia D; Aslibekyan, Stella; Claas, Steven A; Tsai, Michael Y; Borecki, Ingrid B; Kabagambe, Edmond K; Ordovás, José M; Absher, Devin M; Arnett, Donna K

2016-02-01

Omega-3 PUFAs (n-3 PUFAs) reduce IL-6 gene expression, but their effects on transcription regulatory mechanisms are unknown. We aimed to conduct an integrated analysis with both population and in vitro studies to systematically explore the relationships among n-3 PUFA, DNA methylation, single nucleotide polymorphisms (SNPs), gene expression, and protein concentration of IL6. Using data in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study and the Encyclopedia of DNA Elements (ENCODE) consortium, we found that higher methylation of IL6 promoter cg01770232 was associated with higher IL-6 plasma concentration (p = 0.03) and greater IL6 gene expression (p = 0.0005). Higher circulating total n-3 PUFA was associated with lower cg01770232 methylation (p = 0.007) and lower IL-6 concentration (p = 0.02). Moreover, an allele of IL6 rs2961298 was associated with higher cg01770232 methylation (p = 2.55 × 10(-7) ). The association between n-3 PUFA and cg01770232 methylation was dependent on rs2961298 genotype (p = 0.02), but higher total n-3 PUFA was associated with lower cg01770232 methylation in the heterozygotes (p = 0.04) not in the homozygotes. Higher n-3 PUFA is associated with lower methylation at IL6 promoter, which may be modified by IL6 SNPs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Low-fat pork liver pâtés enriched with n-3 PUFA/konjac gel: dynamic rheological properties and technological behaviour during chill storage.

PubMed

Delgado-Pando, G; Cofrades, S; Ruiz-Capillas, C; Triki, M; Jiménez-Colmenero, F

2012-09-01

Low-fat pork liver pâtés enriched with n-3 PUFA/konjac gel were formulated by replacing (total or partially) pork backfat by a combination of healthier oils (olive, linseed and fish oils) and konjac gel. Dynamic rheological properties and technological behaviour of pâtés during chill storage (2 °C, 85 days) were analysed. Cooking yields were affected (P<0.05) by formulation, with percentages ranging between 88 and 98%. According to the frequency sweep test, pâtés presented a gel/emulsion-like pattern with a loosely-structured network and the consistency of a viscoelastic gel. Thermal processing caused the formation of a protein gel network with a considerable element of emulsion-like characteristics. Pâtés became lighter and less red (P<0.05) during chill storage. Purge losses of around 1% were observed at the end of the storage period, irrespective of formulation. Textural parameters of pâtés were affected by formulation and storage time. The results suggest that the replacement of pork back fat by oil-in-water emulsion and the incorporation of konjac gel could provide a mixture of ingredients that effectively mimics the normal animal fat content in pâtés. Copyright © 2012 Elsevier Ltd. All rights reserved.
Effect of omega-3 polyunsaturated fatty acids on the cytoskeleton: an open-label intervention study.

PubMed

Schmidt, Simone; Willers, Janina; Riecker, Sabine; Möller, Katharina; Schuchardt, Jan Philipp; Hahn, Andreas

2015-02-14

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) show beneficial effects on cardiovascular health and cognitive functions, but the underlying molecular mechanisms are not completely understood. Because of the fact that cytoskeleton dynamics affect almost every cellular process, the regulation of cytoskeletal dynamics could be a new pathway by which n-3 PUFAs exert their effects on cellular level. A 12-week open-label intervention study with 12 healthy men was conducted to determine the effects of 2.7 g/d n-3 PUFA on changes in mRNA expression of cytoskeleton-associated genes by quantitative real-time PCR in whole blood. Furthermore, the actin content in red blood cells was analyzed by immunofluorescence imaging. N-3 PUFA supplementation resulted in a significant down-regulation of cytoskeleton-associated genes, in particular three GTPases (RAC1, RHOA, CDC42), three kinases (ROCK1, PAK2, LIMK), two Wiskott-Aldrich syndrome proteins (WASL, WASF2) as well as actin related protein 2/3 complex (ARPC2, ARPC3) and cofilin (CFL1). Variability in F-actin content between subjects was high; reduced actin content was only reduced within group evaluation. Reduced cytoskeleton-associated gene expression after n-3 PUFA supplementation suggests that regulation of cytoskeleton dynamics might be an additional way by which n-3 PUFAs exert their cellular effects. Concerning F-actin, this analysis did not reveal unmistakable results impeding a generalized conclusion.
Production and characterisation of reduced-fat and PUFA-enriched Burrata cheese.

PubMed

Trani, Antonio; Gambacorta, Giuseppe; Gomes, Tommaso F; Loizzo, Pasqua; Cassone, Angela; Faccia, Michele

2016-05-01

Burrata is an Italian fresh 'pasta filata' cheese made from cow's milk and cream that is rapidly spreading in Europe. It has very high caloric content, and a technological protocol was developed for producing a reduced-fat type and fortifying it with polyunsaturated fatty acids (PUFA) of vegetable origin. A satisfactory reduced-fat prototype was obtained by using a 14% fat cream, which was specifically developed by diluting double cream with a suspension of carob seed flour. The composition of the new cheese changed with respect to the control, but the sensory characteristics were not impaired. Moisture increased from 62·6 to 68·4%, fat on dry matter decreased from 59·1 to 34·7%, and the caloric content decreased from 1060·8 to 718 J/100 g. Proteolysis and lipolysis were not affected by the technological modifications: after 7 d storage, the electrophoretic pattern of caseins and the free fatty acids profile of experimental and control cheeses were not significantly different. Fortification of reduced-fat Burrata with PUFA was obtained by using two commercial formulates available at a compatible price with the current economic values of the cheese. The two formulates derived from flaxseeds and Carthamus tinctorius oil and allowed enrichment in C18 :3 : n3 (α-linolenic acid, ALA), and 9cis,11trans- and 10trans,12cis- conjugated linoleic acid (CLA), respectively. Fortification was easy to perform under a technical point of view, but the negative sensory impact limited fortification at a maximum of 7·0 mg g-1 fat ALA and 6·8 g-1 fat CLA.
Reverse association of omega-3/omega-6 polyunsaturated fatty acids ratios with carotid atherosclerosis in patients on hemodialysis.

PubMed

Umemoto, Norio; Ishii, Hideki; Kamoi, Daisuke; Aoyama, Toru; Sakakibara, Takashi; Takahashi, Hiroshi; Tanaka, Akihito; Yasuda, Yoshinari; Suzuki, Susumu; Matsubara, Tatsuaki; Murohara, Toyoaki

2016-06-01

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are widely recognized to have beneficial effects against cardiovascular disease. We investigated the association of n-3 PUFAs levels with carotid atherosclerosis in patients on hemodialysis (HD), who are at high risk for cardiovascular events. Carotid ultra-sound was performed in a total of 461 patients on HD (male 67%, age 67 ± 12years, diabetes rate 46%). Intima-media thickness (IMT) and the plaque score (PS) in carotid arteries were measured. Carotid atherosclerosis was defined as IMT >1.2 mm and/or PS > 5.0. The levels of n-6 PUFAs [dihomo-gamma-linolenic acid (DHLA) and arachidonic acid (AA)] and n-3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] were also measured prior to carotid ultra-sound. Carotid atherosclerosis was observed in 94 patients (20.4%). Individual PUFAs levels were comparable between patients with and without carotid atherosclerosis. However, the ratio of EPA/AA and that of n-3/n-6 PUFAs were significantly lower in patients with carotid atherosclerosis compared to those without (median 0.36 vs. 0.41, p = 0.031 and 0.85 vs. 0.93, p = 0.041, respectively]. After adjustment for other confounders, the ratio of EPA/AA (OR 0.30, 95% CI 0.12-0.70, p = 0.0055) and the ratio of n-3/n-6 PUFAs (OR 0.45, 95% CI 0.25-0.80, p = 0.0066) showed an independent reverse association with carotid atherosclerosis. In addition, the area under receiver-operating characteristic curves for carotid atherosclerosis was significantly greater in an established risk model with EPA/AA and n-3/n-6 ratios than in the established risk model alone. These data suggest that low ratios of both EPA/AA ratio and n-3/n-6 PUFAs were closely associated with carotid atherosclerosis in patients on HD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Thraustochytrids can be grown in low-salt media without affecting PUFA production.

PubMed

Shabala, Lana; McMeekin, Tom; Shabala, Sergey

2013-08-01

Marine microheterotrophs thraustochytrids are emerging as a potential source for commercial production of polyunsaturated fatty acids (PUFA) that have nutritional and pharmacological values. With prospective demand for PUFAs increasing, biotechnological companies are looking for potential increases in those valuable products. However, high levels of NaCl in the culture media required for optimal thraustochytrid growth and PUFA production poses a significant problem to the biotechnological industry due to corrosion of fermenters calling for a need to reduce the amount of NaCl in the culture media, without imposing penalties on growth and yield of cultured organisms. Earlier, as reported by Shabala et al. (Environ Microbiol 11:1835-1843, 2009), we have shown that thraustochytrids use sodium predominantly for osmotic adjustment purposes and, as such, can be grown in low-salt environment without growth penalties, providing the media osmolality is adjusted. In this study, we verify if that conclusion, made for one specific strain and osmolyte only, is applicable to the larger number of strains and organic osmotica, as well as address the issue of yield quality (e.g., PUFA production in low-saline media). Using mannitol and sucrose for osmotic adjustment of the growth media enabled us to reduce NaCl concentration down to 1 mM; this is 15-100-fold lower than any method proposed so far. At the same time, the yield of essential PUFAs was increased by 15 to 20 %. Taken together, these results suggest that the proposed method can be used in industrial fermenters for commercial PUFA production.
Fortification of foods with omega-3 polyunsaturated fatty acids.

PubMed

Ganesan, Balasubramanian; Brothersen, Carl; McMahon, Donald J

2014-01-01

A $600 million nutritional supplements market growing at 30% every year attests to consumer awareness of, and interests in, health benefits attributed to these supplements. For over 80 years the importance of polyunsaturated fatty acid (PUFA) consumption for human health has been established. The FDA recently approved the use of ω-3 PUFAs in supplements. Additionally, the market for ω-3 PUFA ingredients grew by 24.3% last year, which affirms their popularity and public awareness of their benefits. PUFAs are essential for normal human growth; however, only minor quantities of the beneficial ω-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are synthesized by human metabolism. Rather PUFAs are obtained via dietary or nutritional supplementation and modified into other beneficial metabolites. A vast literature base is available on the health benefits and biological roles of ω-3 PUFAs and their metabolism; however, information on their dietary sources and palatability of foods incorporated with ω-3 PUFAs is limited. DHA and EPA are added to many foods that are commercially available, such as infant and pet formulae, and they are also supplemented in animal feed to incorporate them in consumer dairy, meat, and poultry products. The chief sources of EPA and DHA are fish oils or purified preparations from microalgae, which when added to foods, impart a fishy flavor that is considered unacceptable. This fishy flavor is completely eliminated by extensively purifying preparations of n-3 PUFA sources. While n-3 PUFA lipid autoxidation is considered the main cause of fishy flavor, the individual oxidation products identified thus far, such as unsaturated carbonyls, do not appear to contribute to fishy flavor or odor. Alternatively, various compound classes such as free fatty acids and volatile sulfur compounds are known to impart fishy flavor to foods. Identification of the causative compounds to reduce and eventually eliminate fishy flavor is important
Omega-3 fatty acids for depression in adults

PubMed Central

Appleton, Katherine M; Sallis, Hannah M; Perry, Rachel; Ness, Andrew R; Churchill, Rachel

2017-01-01

Background Major depressive disorder (MDD) is highly debilitating, difficult to treat, has a high rate of recurrence, and negatively impacts the individual and society as a whole. One emerging potential treatment for MDD is n-3 polyunsaturated fatty acids (n-3PUFAs), also known as omega-3 oils, naturally found in fatty fish, some other seafood, and some nuts and seeds. Various lines of evidence suggest a role for n-3PUFAs in MDD, but the evidence is far from conclusive. Reviews and meta-analyses clearly demonstrate heterogeneity between studies. Investigations of heterogeneity suggest differential effects of n-3PUFAs, depending on severity of depressive symptoms, where no effects of n-3PUFAs are found in studies of individuals with mild depressive symptomology, but possible benefit may be suggested in studies of individuals with more severe depressive symptomology. Objectives To assess the effects of n-3 polyunsaturated fatty acids (also known as omega-3 fatty acids) versus a comparator (e.g. placebo, anti-depressant treatment, standard care, no treatment, wait-list control) for major depressive disorder (MDD) in adults. Search methods We searched the Cochrane Depression, Anxiety and Neurosis Review Group’s Specialised Registers (CCDANCTR) and International Trial Registries over all years to May 2015. We searched the database CINAHL over all years of records to September 2013. Selection criteria We included studies in the review if they: were a randomised controlled trial; provided n-3PUFAs as an intervention; used a comparator; measured depressive symptomology as an outcome; and were conducted in adults with MDD. Primary outcomes were depressive symptomology (continuous data collected using a validated rating scale) and adverse events. Secondary outcomes were depressive symptomology (dichotomous data on remission and response), quality of life, and failure to complete studies. Data collection and analysis We used standard methodological procedures as expected by
The effect of omega-3 fatty acids on central nervous system remyelination in fat-1 mice.

PubMed

Siegert, Elise; Paul, Friedemann; Rothe, Michael; Weylandt, Karsten H

2017-01-24

There is a large body of experimental evidence suggesting that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are capable of modulating immune function. Some studies have shown that these PUFAs might have a beneficial effect in patients suffering form multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system (CNS). This could be due to increased n-3 PUFA-derived anti-inflammatory lipid mediators. In the present study we tested the effect of an endogenously increased n-3 PUFA status on cuprizone-induced CNS demyelination and remyelination in fat-1 mice versus their wild-type (wt) littermates. Fat-1 mice express an n-3 desaturase, which allows them to convert n-6 PUFAs into n-3 PUFAs. CNS lipid profiles in fat-1 mice showed a significant increase of eicosapentaenoic acid (EPA) levels but similar docosahexaenoic acid levels compared to wt littermates. This was also reflected in significantly higher levels of monohydroxy EPA metabolites such as 18-hydroxyeicosapentaenoic acid (18-HEPE) in fat-1 brain tissue. Feeding fat-1 mice and wt littermates 0.2% cuprizone for 5 weeks caused a similar degree of CNS demyelination in both groups; remyelination was increased in the fat-1 group after a recovery period of 2 weeks. However, at p = 0.07 this difference missed statistical significance. These results indicate that n-3 PUFAs might have a role in promotion of remyelination after toxic injury to CNS oligodendrocytes. This might occur either via modulation of the immune system or via a direct effect on oligodendrocytes or neurons through EPA-derived lipid metabolites such as 18-HEPE.
Potential therapeutic impact of omega-3 long chain-polyunsaturated fatty acids on inflammation markers in Duchenne muscular dystrophy: A double-blind, controlled randomized trial.

PubMed

Rodríguez-Cruz, Maricela; Cruz-Guzmán, Oriana Del Rocío; Almeida-Becerril, Tomás; Solís-Serna, Alan Donovan; Atilano-Miguel, Salvador; Sánchez-González, Juan Raúl; Barbosa-Cortés, Lourdes; Ruíz-Cruz, Eugenia Dolores; Huicochea, Juan Carlos; Cárdenas-Conejo, Alan; Escobar-Cedillo, Rosa Elena; Yam-Ontiveros, Carlos Alberto; Ricárdez-Marcial, Edgar F

2017-09-23

Duchenne Muscular Dystrophy (DMD) is the most frequent dystrophy in childhood generated by a deficiency in dystrophin. DMD is a neuromuscular disease and its clinical course comprises chronic inflammation and gradual muscle weakness. Supplementation of omega-3 long chain-Polyunsaturated Fatty Acids (ω-3 long chain-PUFA) reduces inflammatory markers in various disorders. The goal of this research was to analyze the influence of ω-3 long chain-PUFA intake on gene expression and blood inflammatory markers in boys with DMD. In a placebo-controlled, double. Blind, randomized trial, boys with DMD (n = 36) consumed 2.9 g/day of ω-3 long chain-PUFA or sunflower oil as control, in capsules, for a period of 6 months. Blood was analyzed at baseline and at months 1, 2, 3, and 6 of supplementation for expression of inflammatory markers in leukocytes and serum. There was high adherence to capsule intake (control: 95.3% ± 7.2%, and ω-3 long chain-PUFA: 97.4% ± 3.7% at month 6). Enrichment of EicosaPentaenoic Acid (EPA) and DocosaHexaenoic Acid (DHA) in erythrocytes increased significantly in patients supplemented with ω-3 long chain-PUFA compared with the placebo group during the 6 months of supplementation. Messenger RNA (mRNA) of the Nuclear Factor kappa beta (NF-κB) and its target genes InterLeukin 1 beta (IL-1β) and IL-6 was downregulated significantly (p < 0.05) in leukocytes from DMD boys supplemented with ω-3 long chain-PUFA for 6 months, compared to the placebo group. Omega-3 long chain-PUFA intake decreased the serum IL-1β (-59.5%; p = 0.011) and IL-6 (-54.8%; p = 0.041), and increased the serum IL-10 (99.9%, p < 0.005), in relation to those with placebo treatment. Supplementation with ω-3 long chain-PUFA 2.9 g/day is well-tolerated, has a beneficial reductive effect on proinflammatory markers, and increases an anti-inflammatory marker, indicating that ω-3 long chain-PUFA could have a potential therapeutic impact on chronic inflammation in
Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice

PubMed Central

Merkel, Martin; Velez-Carrasco, Wanda; Hudgins, Lisa C.; Breslow, Jan L.

2001-01-01

Heart-healthy dietary recommendations include decreasing the intake of saturated fatty acids (SFA). However, the relative benefit of replacing SFA with monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), or carbohydrates (CARB) is still being debated. We have used two mouse models of atherosclerosis, low density lipoprotein receptor-deficient (LDLRKO) and apolipoprotein E-deficient (apoEKO) mice to measure the effects of four isocaloric diets enriched with either SFA, MUFA, PUFA, or CARB on atherosclerotic lesion area and lipoprotein levels. In LDLRKO mice, compared with the SFA diet, the MUFA and CARB diets significantly increased atherosclerosis in both sexes, but the PUFA diet had no effect. The MUFA and CARB diets also increased very low density lipoprotein-cholesterol (VLDL-C) and LDL-cholesterol (LDL-C) in males and VLDL-C levels in females. Analysis of data from LDLRKO mice on all diets showed that atherosclerotic lesion area correlated positively with VLDL-C levels (males: r = 0.47, P < 0.005; females: r = 0.52, P < 0.001). In contrast, in apoEKO mice there were no significant dietary effects on atherosclerosis in either sex. Compared with the SFA diet, the CARB diet significantly decreased VLDL-C in males and the MUFA, PUFA, and CARB diets decreased VLDL-C and the CARB diet decreased LDL-C in females. In summary, in LDLRKO mice the replacement of dietary SFA by either MUFA or CARB causes a proportionate increase in both atherosclerotic lesion area and VLDL-C. There were no significant dietary effects on atherosclerotic lesion area in apoEKO mice. These results are surprising and suggest that, depending on the underlying genotype, dietary MUFA and CARB can actually increase atherosclerosis susceptibility, probably by raising VLDL-C levels through a non-LDL receptor, apoE-dependent pathway. PMID:11606787
Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice.

PubMed

Merkel, M; Velez-Carrasco, W; Hudgins, L C; Breslow, J L

2001-11-06

Heart-healthy dietary recommendations include decreasing the intake of saturated fatty acids (SFA). However, the relative benefit of replacing SFA with monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), or carbohydrates (CARB) is still being debated. We have used two mouse models of atherosclerosis, low density lipoprotein receptor-deficient (LDLRKO) and apolipoprotein E-deficient (apoEKO) mice to measure the effects of four isocaloric diets enriched with either SFA, MUFA, PUFA, or CARB on atherosclerotic lesion area and lipoprotein levels. In LDLRKO mice, compared with the SFA diet, the MUFA and CARB diets significantly increased atherosclerosis in both sexes, but the PUFA diet had no effect. The MUFA and CARB diets also increased very low density lipoprotein-cholesterol (VLDL-C) and LDL-cholesterol (LDL-C) in males and VLDL-C levels in females. Analysis of data from LDLRKO mice on all diets showed that atherosclerotic lesion area correlated positively with VLDL-C levels (males: r = 0.47, P < 0.005; females: r = 0.52, P < 0.001). In contrast, in apoEKO mice there were no significant dietary effects on atherosclerosis in either sex. Compared with the SFA diet, the CARB diet significantly decreased VLDL-C in males and the MUFA, PUFA, and CARB diets decreased VLDL-C and the CARB diet decreased LDL-C in females. In summary, in LDLRKO mice the replacement of dietary SFA by either MUFA or CARB causes a proportionate increase in both atherosclerotic lesion area and VLDL-C. There were no significant dietary effects on atherosclerotic lesion area in apoEKO mice. These results are surprising and suggest that, depending on the underlying genotype, dietary MUFA and CARB can actually increase atherosclerosis susceptibility, probably by raising VLDL-C levels through a non-LDL receptor, apoE-dependent pathway.
Experimental Copper Deficiency, Chromium Deficiency and Additional Molybdenum Supplementation in Goats – Pathological Findings

PubMed Central

Aupperle, H; Schoon, HA; Frank, A

2001-01-01

Secondary copper (Cu) deficiency, chromium (Cr) deficiency and molybdenosis (Mo) has been suggested to cause the "mysterious" moose disease in the southwest of Sweden. The present experiment was performed on goats to investigate the clinical, chemical, and pathological alterations after 20 months feeding of a semi-synthetic diet deficient in Cu and Cr. Four groups were included in the study: control group (n = 4), Cu-deficient group (group 1, n = 4), Cr-deficient group (group 2, n = 2) and Cu+Cr-deficient group (group 3, n = 3). Group 3 was additionally supplemented with tetrathiomolybdate during the last 2 months of the experiment. Main histopathological findings in groups 1 and 3 were the lesions in the liver, characterised by a severe active fibrosis, bile duct proliferation, haemosiderosis and mild necroses. Additionally, degenerative alterations of the exocrine pancreas were prominent in groups 1 and 3. Lesions in group 3 were more pronounced than in group 1. In group 3, the skin showed an atrophic dermatosis, while in group 2 a crusty dermatitis caused by Candida spp. was observed. This study shows that liver, pancreas and skin are mainly affected by a long term deficiency of copper and the findings are complicated by molybdenum application while chromium deficiency produced no histomorphological effects in our study. PMID:11887391
Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients.

PubMed

Jacobo-Cejudo, M Gorety; Valdés-Ramos, Roxana; Guadarrama-López, Ana L; Pardo-Morales, Rosa-Virgen; Martínez-Carrillo, Beatriz E; Harbige, Laurence S

2017-06-03

Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n- 3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n- 3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n- 3 PUFA intake was calculated in g/day. Waist circumference and blood glucose showed significant reductions in the FOG group ( p = 0.001 and p = 0.011, respectively). Hb1Ac ( p = 0.009 and p = 0.004), leptin ( p < 0.000 and p < 0.000), and leptin/adiponectin ratio ( p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols ( p = 0.002) and atherogenic index ( p = 0.031); in contrast, the PG group had increased total cholesterol ( p < 0.000), non-HDL cholesterol ( p < 0.000), and atherogenic index ( p = 0.017). We found a beneficial effect of n- 3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups.
Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients

PubMed Central

Jacobo-Cejudo, M. Gorety; Valdés-Ramos, Roxana; Guadarrama-López, Ana L.; Pardo-Morales, Rosa-Virgen; Martínez-Carrillo, Beatriz E.; Harbige, Laurence S.

2017-01-01

Background: Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n-3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n-3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. Methods: In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n-3 PUFA intake was calculated in g/day. Results: Waist circumference and blood glucose showed significant reductions in the FOG group (p = 0.001 and p = 0.011, respectively). Hb1Ac (p = 0.009 and p = 0.004), leptin (p < 0.000 and p < 0.000), and leptin/adiponectin ratio (p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols (p = 0.002) and atherogenic index (p = 0.031); in contrast, the PG group had increased total cholesterol (p < 0.000), non-HDL cholesterol (p < 0.000), and atherogenic index (p = 0.017). Conclusions: We found a beneficial effect of n-3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups. PMID:28587203
Omega-3 polyunsaturated fatty acids in treating non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial.

PubMed

Nogueira, Monize Aydar; Oliveira, Claudia Pinto; Ferreira Alves, Venâncio Avancini; Stefano, José Tadeu; Rodrigues, Lívia Samara Dos Reis; Torrinhas, Raquel Susana; Cogliati, Bruno; Barbeiro, Hermes; Carrilho, Flair José; Waitzberg, Dan Linetzky

2016-06-01

& aims: Few clinical trials have addressed the potential benefits of omega-3 polyunsaturated fatty acids (PUFAs) on non-alcoholic steatohepatitis (NASH). We evaluated the effects of supplementation with omega-3 PUFAs from flaxseed and fish oils in patients with biopsy-proven NASH. Patients received three capsules daily, each containing 0.315 g of omega-3 PUFAs (64% alpha-linolenic [ALA], 16% eicosapentaenoic [EPA], and 21% docosahexaenoic [DHA] acids; n-3 group, n = 27) or mineral oil (placebo group, n = 23). Liver biopsies were evaluated histopathologically by the NASH activity score (NAS). Plasma levels of omega-3 PUFAs were assessed as a marker of intake at baseline and after 6 months of treatment. Secondary endpoints included changes in plasma biochemical markers of lipid metabolism, inflammation, and liver function at baseline and after 3 and 6 months of treatment. At baseline, NAS was comparable between the groups (p = 0.98). After intervention with omega-3 PUFAs, plasma ALA and EPA levels increased (p ≤ 0.05). However in the placebo group, we also observed increased EPA and DHA (p ≤ 0.05), suggesting an off-protocol intake of PUFAs. NAS improvement/stabilization was correlated with increased ALA in the n-3 group (p = 0.02) and with increased EPA (p = 0.04) and DHA (p = 0.05) in the placebo group. Triglycerides were reduced after 3 months in the n-3 group compared to baseline (p = 0.01). In NASH patients, the supplementation of omega-3 PUFA from flaxseed and fish oils significantly impacts on plasma lipid profile of patients with NASH. Plasma increase of these PUFAs was associated with better liver histology. (ID 01992809). Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Omega-3 Fatty Acids, Depressive Symptoms, and Cognitive Performance in Patients With Coronary Artery Disease

PubMed Central

Mazereeuw, Graham; Herrmann, Nathan; Oh, Paul I.; Ma, David W.L.; Wang, Cheng Tao; Kiss, Alexander; Lanctôt, Krista L.

2016-01-01

Abstract This trial investigated the efficacy of omega-3 polyunsaturated fatty acid (n-3 PUFA) treatment for improving depressive symptoms and cognitive performance in patients with coronary artery disease (CAD) participating in cardiac rehabilitation. Patients with CAD aged 45 to 80 years were randomized to receive either 1.9-g/d n-3 PUFA treatment or placebo for 12 weeks. Depressive symptoms were measured using the Hamilton Depression Rating Scale (HAM-D, primary outcome) and the Beck Depression Inventory II (BDI-II). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were used to identify a depressive episode at baseline. Cognitive performance was measured using a standardized battery for vascular cognitive impairment. In 92 patients (age, 61.7 ± 8.7 y; 76% male, 40% depressed; HAM-D, 6.9 ± 5.9; BDI-II, 12.3 ± 10.9; n = 45 n-3 PUFA, n = 47 placebo), depression decreased (HAM-D, F3,91 = 2.71 and P = 0.049; BDI-II, F3,91 = 6.24 and P < 0.01), and cognitive performance improved (attention/processing speed, F1,91 = 5.57, P = 0.02; executive function, F1,91 = 14.64, P < 0.01; visuospatial memory, F1,91 = 4.01, P = 0.04) over cardiac rehabilitation. Omega-3 PUFA treatment increased plasma eicosapentaenoic acid (F1,29 = 33.29, P < 0.01) and docosahexaenoic acid (F1,29 = 15.29, P < 0.01) concentrations but did not reduce HAM-D (F3,91 = 1.59, P = 0.20) or BDI-II (F3,91 = 0.46, P = 0.50) scores compared with placebo. Treatment did not improve cognitive performance; however, n-3 PUFAs significantly increased verbal memory compared with placebo in a subgroup of nondepressed patients (F1,54 = 4.16, P = 0.04). This trial suggests that n-3 PUFAs do not improve depressive and associated cognitive symptoms in those with CAD. The possible benefits of n-3 PUFAs for verbal memory may warrant investigation in well-powered studies. PMID:27529771
PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity.

PubMed

Jans, Anneke; Konings, Ellen; Goossens, Gijs H; Bouwman, Freek G; Moors, Chantalle C; Boekschoten, Mark V; Afman, Lydia A; Müller, Michael; Mariman, Edwin C; Blaak, Ellen E

2012-04-01

Dietary fat quality may influence skeletal muscle lipid processing and fat accumulation, thereby modulating insulin sensitivity. The objective was to examine the acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA processing and postprandial insulin sensitivity in obese, insulin-resistant men. In a single-blind, randomized, crossover study, 10 insulin-resistant men consumed 3 high-fat mixed meals (2.6 MJ), which were high in SFAs, MUFAs, or PUFAs. Fasting and postprandial skeletal muscle FA processing was examined by measuring differences in arteriovenous concentrations across the forearm muscle. [²H₂]Palmitate was infused intravenously to label endogenous triacylglycerol and FFAs in the circulation, and [U-¹³C]palmitate was added to the meal to label chylomicron-triacylglycerol. Skeletal muscle biopsy samples were taken to assess intramuscular lipid metabolism and gene expression. Insulin and glucose responses (AUC) after the SFA meal were significantly higher than those after the PUFA meal (P = 0.006 and 0.033, respectively). Uptake of triacylglycerol-derived FAs was lower in the postprandial phase after the PUFA meal than after the other meals (AUC₆₀₋₂₄₀; P = 0.02). The fractional synthetic rate of the triacylglycerol, diacylglycerol, and phospholipid pool was higher after the MUFA meal than after the SFA meal. PUFA induced less transcriptional downregulation of oxidative pathways than did the other meals. PUFAs reduced triacylglycerol-derived skeletal muscle FA uptake, which was accompanied by higher postprandial insulin sensitivity, a more transcriptional oxidative phenotype, and altered intramyocellular lipid partitioning and may therefore be protective against the development of insulin resistance.
Omega 3 polyunsaturated fatty acid improves spatial learning and hippocampal Peroxisome Proliferator Activated Receptors (PPARα and PPARγ) gene expression in rats

PubMed Central

2012-01-01

Background This study examined the effects of dietary polyunsaturated fatty acids (PUFA) as different n-6: n-3 ratios on spatial learning and gene expression of peroxisome- proliferator-activated receptors (PPARs) in the hippocampus of rats. Thirty male Sprague–Dawley rats were randomly allotted into 3 groups of ten animals each and received experimental diets with different n-6: n-3 PUFA ratios of either 65:1, 22:1 or 4.5:1. After 10 weeks, the spatial memory of the animals was assessed using the Morris Water Maze test. The expression of PPARα and PPARγ genes were determined using real-time PCR. Results Decreasing dietary n-6: n-3 PUFA ratios improved the cognitive performance of animals in the Morris water maze test along with the upregulation of PPARα and PPARγ gene expression. The animals with the lowest dietary n-6: n-3 PUFA ratio presented the highest spatial learning improvement and PPAR gene expression. Conclusion It can be concluded that modulation of n-6: n-3 PUFA ratios in the diet may lead to increased hippocampal PPAR gene expression and consequently improved spatial learning and memory in rats. PMID:22989138

Food frequency questionnaire as an indicator of the serum composition of essential n-3 and n-6 polyunsaturated fatty acids in early pregnancy, according to body mass index.

PubMed

Lepsch, J; Vaz, J S; Moreira, J D; Pinto, T J P; Soares-Mota, M; Kac, G

2015-02-01

We investigated whether food frequency questionnaire (FFQ) may be indicative of the serum composition of essential n-3 and n-6 polyunsaturated fatty acids (PUFAs) in early pregnancy and if correlations are affected by body mass index (BMI). The present study comprised a prospective cohort conducted in Rio de Janeiro, Brazil. The sample was composed of 248 women, aged 20-40 years, between 6 and the 13 weeks of gestation. Dietary intake was assessed using a validated FFQ. Fatty acid serum compositions were determined in fasting serum samples, employing a high-throughput robotic direct methylation coupled with fast gas-liquid chromatography. Spearman's correlation (r(s)) was used to assess the relationship between fatty acid intake and corresponding serum composition. Women were classified according to BMI (kg m(-2) ) as underweight/normal weight (BMI < 25 kg m(-2) ; n = 139) or excessive weight (BMI ≥ 25 kg m(-2) ; n = 109). In the total sample, dietary report was significantly correlated with the serum composition of total polyunsaturated fatty acid (PUFA; r(s) = 0.232, P < 0.001), linoleic acid (LA; 18:2n-6; r(s) = 0.271, P < 0.001), eicosapentaenoic acid (EPA; 20:5n-3; r(s) = 0.263, P < 0.001) and docosahexaenoic acid (DHA; 22:6n-3; r(s) = 0.209, P = 0.001). When analyses were stratified by BMI, significant correlations between FFQ and serum composition among underweight/normal weight women were observed for total PUFA (r(s) = 0.323, P < 0.001), LA (r(s) = 0.322, P < 0.001), EPA (r(s) = 0.352, P < 0.001) and DHA (r(s) = 0.176, P = 0.039). Among women of excessive weight, significant correlations were observed only for alpha linolenic acid (ALA; 18:3n-3; r(s) = 0.199, P = 0.040) and DHA (r(s) = 0.236, P = 0.014). FFQ in early pregnancy may be used as a possible indicator of serum concentrations of fatty acids. Higher correlations were observed among underweight/normal weight women. © 2014 The British Dietetic Association Ltd.
Differential effects of n-3 polyunsaturated fatty acids on metabolic control and vascular reactivity in the type 2 diabetic ob/ob mouse.

PubMed

Mustad, Vikkie A; Demichele, Stephen; Huang, Yung-Sheng; Mika, Amanda; Lubbers, Nathan; Berthiaume, Nathalie; Polakowski, Jim; Zinker, Brad

2006-10-01

Diets rich in monounsaturated fatty acids (MUFA) are recommended for individuals with type 2 diabetes mellitus (T2DM). The American Heart Association recommends increasing intakes of n-3 polyunsaturated fatty acids (PUFA) to reduce the risk of vascular disease in high-risk individuals; however, the long-term effects of these bioactive fatty acids on glucose metabolism in insulin resistance are controversial. The present studies were conducted to evaluate the effects of diets rich in both MUFA and alpha linolenic acid (C18:3n-3, ALA), eicosapentaenoic acid (C20:5n-3, EPA), or docosahexaenoic acid (C22:6n-3, DHA), on glycemic control and other parameters related to vascular health in a mouse model of T2DM and insulin resistance. Male ob/ob mice (n = 15 per treatment) were fed 1 of 4 lipid-modified formula diets (LFDs) for 4 weeks: (1) MUFA control, (2) ALA blend, (3) EPA blend, and (4) DHA blend. A portion of a MUFA-rich lipid blend in the control LFD was replaced with 11% to 14% energy as n-3 PUFA. After 4 weeks, plasma glucose response to a standard meal (1.5 g carbohydrate/kg body weight) and insulin challenge (2 U/kg body weight, IP) was assessed, and samples were collected for analysis of glucose, insulin, and lipids. Vascular reactivity of isolated aortic rings was assessed in an identical follow-up study. The results showed that insulin-resistant mice fed an LFD with EPA and/or DHA blends had significantly (P < .05) lower triglycerides and free fatty acids, but insulin sensitivity and fasting plasma glucose were not improved. However, mice fed with the ALA blend had significantly improved insulin sensitivity when compared to those fed with other LFD (P < .05). Animals fed an LFD with n-3 PUFA from marine or plant sources showed significantly improved vascular responses as compared with the MUFA-rich LFD (E(max), P < .05) and ob/ob reference mice consuming chow (E(max) and pEC(50), P < .05). In summary, long-term consumption of LFD with n-3 PUFAs improved blood
n-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD.

PubMed

Vauzour, David; Rodriguez-Ramiro, Ildefonso; Rushbrook, Simon; Ipharraguerre, Ignacio R; Bevan, Damon; Davies, Susan; Tejera, Noemi; Mena, Pedro; de Pascual-Teresa, Sonia; Del Rio, Daniele; Gavrilovic, Jelena; Minihane, Anne Marie

2018-01-01

Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults and at present no licensed medication has been approved. Despite its complex patho-physiology, dietary strategies aiming at delaying or preventing NAFLD have taken a reductionist approach, examining the impact of single components. Accumulating evidence suggests that n-3 LC-PUFAs are efficacious in regulating lipogenesis and fatty acid oxidation. In addition, plant derived flavonoids are also emerging as a dietary strategy for NAFLD prevention, with efficacy attributed to their insulin sensitising and indirect antioxidant effects. Based on knowledge of their complementary molecular targets, we aimed to demonstrate that the combination of n-3 LC-PUFA (n-3) and flavan-3-ols (FLAV) prevents NAFLD. In a high-fat high-fructose (HF/HFr) fed C57Bl/6J mouse model, the independent and interactive impact of n-3 and FLAV on histologically defined NAFLD, insulin sensitivity, weight gain, intestinal and hepatic gene expression, intestinal bile acids were examined. Only the combination of FLAV and n-3 (FLAVn-3) prevented steatosis as evidenced by a strong reduction in hepatocyte ballooning. While FLAV reduced body (-28-30%), adipose tissue (-45-50%) weights and serum insulin (-22-25%) as observed following an intra-peritoneal glucose tolerance test, n-3 downregulated the expression of Srebf1 and the lipogenic genes (Acaca, Fasn). Significant impacts of interventions on intestinal bile acid metabolism, farnesoid X receptor (Fxr) signalling in the intestine and liver, and hepatic expression of fatty acid transporters (Fabp4, Vldlr, Cd36) were also evident. FLAVn-3 may be a novel intervention for NAFLD. Future research should aim to demonstrate its efficacy in the prevention and treatment of human NAFLD. Copyright © 2017 Elsevier B.V. All rights reserved.
The effects of n-3 fatty acid deficiency and repletion upon the fatty acid composition and function of the brain and retina.

PubMed

Connor, W E; Neuringer, M

1988-01-01

It is now apparent that both n-6 and n-3 fatty acids are essential for normal development in mammals, and that each has specific functions in the body. N-6 fatty acids are necessary primarily for growth, reproduction, and the maintenance of skin integrity, whereas n-3 fatty acids are involved in the development and function of the retina and cerebral cortex and perhaps other organs such as the testes. Fetal life and infancy are particularly critical for the nervous tissue development. Therefore, with respect to human nutrition, adequate amounts of omega-3 fatty acids should be provided during pregnancy, lactation and infancy, but probably throughout life. We estimate that adequate levels are provided by diets containing 6-8% kcals from linoleic acid and 1% from n-3 fatty acids (alpha-linolenic acid, EPA and DHA), resulting in a ratio of n-6 to n-3 fatty acids of 4:1 to 10:1. The essentiality of n-3 fatty acids resides in their presence as DHA in vital membranes of the photoreceptors of the retina and the synaptosomes and other subcellular membranes of the brain. The replacement of DHA in deficient animals by the n-6 fatty acid, 22:5, results in abnormal functioning of the membranes for reasons as yet to be ascertained. Most significant is the lability of fatty acid composition in the retinal and brain of deficient animals. Dietary fish oil, which contains EPA and DHA, will readily lead to a change in the composition of the membrane of retina and brain, fatty acids, with DHA replacing the n-6 fatty acid, 22:5. The interrelationships between the chemistry of neural and retinal membranes as affected by diet and their biological functioning provides an exciting prospect for future investigations.
Human Milk Plasmalogens Are Highly Enriched in Long-Chain PUFAs.

PubMed

Moukarzel, Sara; Dyer, Roger A; Keller, Bernd O; Elango, Rajavel; Innis, Sheila M

2016-11-01

Human milk contains unique glycerophospholipids, including ethanolamine-containing plasmalogens (Pls-PEs) in the milk fat globule membrane, which have been implicated in infant brain development. Brain Pls-PEs accumulate postnatally and are enriched in long-chain polyunsaturated fatty acids (LC-PUFAs), particularly docosahexaenoic acid (DHA). Fatty acid (FA) composition of Pls-PEs in milk is poorly understood because of the analytical challenges in separating Pls-PEs from other phospholipids in the predominating presence of triacylglycerols. The variability of Pls-PE FAs and the potential role of maternal diet remain unknown. Our primary objectives were to establish improved methodology for extracting Pls-PEs from human milk, enabling FA analysis, and to compare FA composition between Pls-PEs and 2 major milk phospholipids, phosphatidylcholine and phosphatidylethanolamine. Our secondary objective was to explore associations between maternal DHA intake and DHA in milk phospholipids and variability in phospholipid-DHA within a woman. Mature milk was collected from 25 women, with 4 providing 3 milk samples on 3 separate days. Lipids were extracted, and phospholipids were removed by solid phase extraction. Pls-PEs were separated by using normal-phase HPLC, recovered and analyzed for FAs by GLC. Diet was assessed by using a validated food-frequency questionnaire. Pls-PE concentration in human milk was significantly higher in LC-PUFAs than phosphatidylethanolamine and phosphatidylcholine, including arachidonic acid (AA) and DHA. The mean ± SD concentration of AAs in Pls-PEs was ∼2.5-fold higher than in phosphatidylethanolamine (10.5 ± 1.71 and 3.82 ± 0.92 g/100 g, respectively). DHA in Pls-PEs varied across women (0.95-6.51 g/100 g), likely independent of maternal DHA intake. Pls-PE DHA also varied within a woman across days (CV ranged from 9.8% to 28%). Human milk provides the infant with LC-PUFAs from multiple lipid pools, including a source from Pls-PEs. The
Genome-wide association study of the plasma triglyceride response to an n-3 polyunsaturated fatty acid supplementation.

PubMed

Rudkowska, Iwona; Guénard, Frédéric; Julien, Pierre; Couture, Patrick; Lemieux, Simone; Barbier, Olivier; Calder, Philip C; Minihane, Anne Marie; Vohl, Marie-Claude

2014-07-01

Studies have shown a large interindividual variability in plasma TG response to long-chain n-3 PUFA supplementation, which may likely be attributable to genetic variability within the populations studied. The objective is to compare the frequency of SNPs in a genome-wide association study between responders (reduction in plasma TG levels ≥0.01 mM) and nonresponders (increase in plasma TG of ≥0 mM) to supplementation. Genomic DNA from 141 subjects who completed a 2-week run-in period followed by 6-week supplementation with 5 g of fish oil daily (1.9-2.2 g EPA and 1.1 g DHA daily) were genotyped on Illumina HumanOmni-5-QuadBeadChip. Thirteen loci had frequency differences between responders and nonresponders (P < 1 × 10(-5)), including SNPs in or near IQCJ-SCHIP1, MYB, NELL1, NXPH1, PHF17, and SLIT2 genes. A genetic risk score (GRS) was constructed by summing the number of risk alleles. This GRS explained 21.53% of the variation in TG response to n-3 PUFA supplementation when adjusted for age, sex, and BMI (P = 0.0002). Using Fish Oil Intervention and Genotype as a replication cohort, the GRS was able to explain 2% of variation in TG response when adjusted. In conclusion, subjects who decrease their plasma TG levels following n-3 PUFA supplementation may have a different genetic profile than individuals who do not respond. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.
Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis.

PubMed

de Oliveira Otto, Marcia C; Wu, Jason H Y; Baylin, Ana; Vaidya, Dhananjay; Rich, Stephen S; Tsai, Michael Y; Jacobs, David R; Mozaffarian, Dariush

2013-12-18

Dietary guidelines support intake of polyunsaturated fatty acids (PUFAs) in fish and vegetable oils. However, some controversy remains about benefits of PUFAs, and most prior studies have relied on self-reported dietary assessment in relatively homogeneous populations. In a multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans, Chinese Americans), plasma phospholipid PUFAs were measured at baseline (2000-2002) using gas chromatography and dietary PUFAs estimated using a food frequency questionnaire. Incident cardiovascular disease (CVD) events (including coronary heart disease and stroke; n=189) were prospectively identified through 2010 during 19 778 person-years of follow-up. In multivariable-adjusted Cox models, circulating n-3 eicosapentaenoic acid and docosahexaenoic acid were inversely associated with incident CVD, with extreme-quartile hazard ratios (95% CIs) of 0.49 for eicosapentaenoic acid (0.30 to 0.79; Ptrend=0.01) and 0.39 for docosahexaenoic acid (0.22 to 0.67; Ptrend<0.001). n-3 Docosapentaenoic acid (DPA) was inversely associated with CVD in whites and Chinese, but not in other race/ethnicities (P-interaction=0.01). No significant associations with CVD were observed for circulating n-3 alpha-linolenic acid or n-6 PUFA (linoleic acid, arachidonic acid). Associations with CVD of self-reported dietary PUFA were consistent with those of the PUFA biomarkers. All associations were similar across racial-ethnic groups, except those of docosapentaenoic acid. Both dietary and circulating eicosapentaenoic acid and docosahexaenoic acid, but not alpha-linolenic acid or n-6 PUFA, were inversely associated with CVD incidence. These findings suggest that increased consumption of n-3 PUFA from seafood may prevent CVD development in a multiethnic population.
Effects of dietary polyunsaturated fatty acids and nucleotides on tissue fatty acid profiles of rats with carbon tetrachloride-induced liver damage.

PubMed

Fontana, L; Moreira, E; Torres, M I; Periago, J L; Sánchez de Medina, F; Gil, A

1999-04-01

The deficiency of polyunsaturated fatty acids (PUFA) that occurs in plasma of patients with liver cirrhosis has been assessed in rats with severe steatosis and mild liver necrosis induced by repeated administration of low doses of carbon tetrachloride (CCl(4)). The contribution of both dietary (n-3) long-chain PUFA and nucleotides to the recovery of the altered fatty acid profiles of tissue lipids of these rats has also been studied. Two groups of rats were used. The first was intraperitoneally injected 0.15 ml of a 10% (v/v) CCl(4)solution in paraffin per 100 g of body weight, three times a week for 9 weeks; the second received paraffin alone. After the treatment, six rats of each group were killed. Afterwards, the remaining controls were fed a semipurified diet (SPD) for 3 weeks, and the remaining rats in the CCl(4)group were divided into three new groups: the first was fed the SP diet; the second was fed the SP diet supplemented with 1% (n-3) polyunsaturated fatty acids (PUFA diet); and the third was fed the SP diet supplemented with 250 mg nucleotides per 100 g diet (NT diet). Fatty acids of plasma, erythrocyte membranes and liver microsomes were analyzed. Decreases in linoleic and arachidonic acids in both total plasma lipids and liver microsomal phospholipids were the main findings due to CCl(4)treatment. The rats that received CCl(4)and the PUFA diet showed the lowest levels of (n-6) PUFA and the highest levels of (n-3) PUFA in liver microsomal phospholipids, as well as a significant increase of (n-3) PUFAs in total plasma lipids. The animals that received the NT diet showed no signs of fatty infiltration and exhibited the highest levels of (n-6) PUFAs in liver microsomal phospholipids. These results show that CCl(4)affects fatty acid metabolism which is accordingly reflected in altered tissue fatty acid profiles, and that balanced diets containing PUFA and nucleotides are important for the recovery of the damaged liver in rats. Copyright 1999 Harcourt
Polyunsaturated fat in the methionine-choline-deficient diet influences hepatic inflammation but not hepatocellular injury.

PubMed

Lee, Gene S; Yan, Jim S; Ng, Raymond K; Kakar, Sanjay; Maher, Jacquelyn J

2007-08-01

Methionine-choline-deficient (MCD) diets that cause steatohepatitis in rodents are typically enriched in polyunsaturated fat. To determine whether the fat composition of the MCD formula influences the development of liver disease, we manufactured custom MCD formulas with fats ranging in PUFA content from 2% to 59% and tested them for their ability to induce steatohepatitis. All modified-fat MCD formulas caused identical degrees of hepatic steatosis and resulted in a similar distribution of fat within individual hepatic lipid compartments. The fatty acid composition of hepatic lipids, however, reflected the fat composition of the diet. Mice fed a PUFA-rich MCD formula showed extensive hepatic lipid peroxidation, induction of proinflammatory genes, and histologic inflammation. When PUFAs were substituted with more saturated fats, lipid peroxidation, proinflammatory gene induction, and hepatic inflammation all declined significantly. Despite the close relationship between PUFAs and hepatic inflammation in mice fed MCD formulas, dietary fat had no impact on MCD-mediated damage to hepatocytes. Indeed, histologic apoptosis and serum alanine aminotransferase levels were comparable in all MCD-fed mice regardless of dietary fat content. Together, these results indicate that dietary PUFAs promote hepatic inflammation but not hepatotoxicity in the MCD model of liver disease. These findings emphasize that individual dietary nutrients can make specific contributions to steatohepatitis.
Polyunsaturated Fatty Acid (PUFA) Status in Pregnant Women: Associations with Sleep Quality, Inflammation, and Length of Gestation

PubMed Central

Christian, Lisa M.; Blair, Lisa M.; Porter, Kyle; Lower, Mary; Cole, Rachel M.; Belury, Martha A.

2016-01-01

Mechanistic pathways linking maternal polyunsaturated fatty acid (PUFA) status with gestational length are poorly delineated. This study examined whether inflammation and sleep quality serve as mediators, focusing on the antiinflammatory ω-3 docosahexaenoic acid (DHA; 22:6n3) and proinflammatory ω-6 arachidonic acid (AA; 20:4n6). Pregnant women (n = 135) provided a blood sample and completed the Pittsburgh Sleep Quality Index (PSQI) at 20–27 weeks gestation. Red blood cell (RBC) fatty acid levels were determined by gas chromatography and serum inflammatory markers [interleukin (IL)-6, IL-8, tumor necrosis factor-α, IL-1β, and C-reactive protein] by electrochemiluminescence using high sensitivity kits. Both higher serum IL-8 (95% CI = 0.10,3.84) and poor sleep (95% CI = 0.03,0.28) served as significant mediators linking lower DHA:AA ratios with shorter gestation. Further, a serial mediation model moving from the DHA:AA ratio → sleep → IL-8 → length of gestation was statistically significant (95% CI = 0.02, 0.79). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. No interactions with race were observed in relation to length of gestation as a continuous variable. However, a significant interaction between race and the DHA:AA ratio in predicting preterm birth was observed (p = 0.049); among African Americans only, odds of preterm birth decreased as DHA:AA increased (p = 0.048). These data support a role for both inflammatory pathways and sleep quality in linking less optimal RBC PUFA status with shorter gestation in African American and European American women and suggest that African-Americans have greater risk for preterm birth in the context of a low DHA:AA ratio. PMID:26859301
Hepatoprotective Role of Wheatgrass on Alcohol and ΔPUFA-Induced Oxidative Stress in Rats.

PubMed

Durairaj, Varalakshmi; Shakya, Garima; Rajagopalan, Rukkumani

2015-06-01

Alcohol abuse is recognized as the most common cause for the development of various abnormalities including liver disease. Excessive free radicals are generated during the metabolism of ethanol. The ingestion of alcohol along with polyunsaturated fatty acid (PUFA) aggravates the production of free radicals and enhances the oxidative stress. Medicinal plants contain active phytocomponents, which are the principal healthcare resources. We aimed to analyze the effect of wheatgrass extract on alcohol and thermally oxidized PUFA (ΔPUFA) induced oxidative stress in male albino Wistar rats. The levels of marker enzymes gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), lipid peroxidative markers; thiobarbutric acid reactive substances (TBARS) and lipid hydroperoxides (LH), the levels of enzymatic (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx]) and nonenzymatic (reduced glutathione [GSH], vitamin E, vitamin C) antioxidants were analyzed in liver to evaluate the effects of wheatgrass. The levels of TBARS and LH were significantly (p ≤ .05) increased in alcohol + ΔPUFA group, which were found to be reduced on treatment with wheatgrass. The levels of both enzymatic and nonenzymatic antioxidants were significantly (p ≤ .05) decreased in alcohol + ΔPUFA group, which were found to be restored on treatment with wheatgrass. From the results obtained, we conclude that wheatgrass protects the liver against alcohol and ΔPUFA induced oxidative stress.
Can Early Omega-3 Fatty Acid Exposure Reduce Risk of Childhood Allergic Disease?

PubMed

Miles, Elizabeth A; Calder, Philip C

2017-07-21

A causal link between increased intake of omega-6 ( n -6) polyunsaturated fatty acids (PUFAs) and increased incidence of allergic disease has been suggested. This is supported by biologically plausible mechanisms, related to the roles of eicosanoid mediators produced from the n -6 PUFA arachidonic acid. Fish and fish oils are sources of long chain omega-3 ( n -3) PUFAs. These fatty acids act to oppose the actions of n -6 PUFAs particularly with regard to eicosanoid synthesis. Thus, n -3 PUFAs may protect against allergic sensitisation and allergic manifestations. Epidemiological studies investigating the association between maternal fish intake during pregnancy and allergic outcomes in infants/children of those pregnancies suggest protective associations, but the findings are inconsistent. Fish oil provision to pregnant women is associated with immunologic changes in cord blood. Studies performed to date indicate that provision of fish oil during pregnancy may reduce sensitisation to common food allergens and reduce prevalence and severity of atopic eczema in the first year of life, with a possible persistence until adolescence. A recent study reported that fish oil consumption in pregnancy reduces persistent wheeze and asthma in the offspring at ages 3 to 5 years. Eating oily fish or fish oil supplementation in pregnancy may be a strategy to prevent infant and childhood allergic disease.
A lipidomic study on the regulation of inflammation and oxidative stress targeted by marine ω-3 PUFA and polyphenols in high-fat high-sucrose diets.

PubMed

Dasilva, Gabriel; Pazos, Manuel; García-Egido, Eduardo; Gallardo, José M; Ramos-Romero, Sara; Torres, Josep Lluís; Romeu, Marta; Nogués, María-Rosa; Medina, Isabel

2017-05-01

The ability of polyphenols to ameliorate potential oxidative damage of ω-3 PUFAs when they are consumed together and then, to enhance their potentially individual effects on metabolic health is discussed through the modulation of fatty acids profiling and the production of lipid mediators. For that, the effects of the combined consumption of fish oils and grape seed procyanidins on the inflammatory response and redox unbalance triggered by high-fat high-sucrose (HFHS) diets were studied in an animal model of Wistar rats. A standard diet was used as control. Results suggested that fish oils produced a replacement of ω-6 by ω-3 PUFAs in membranes and tissues, and consequently they improved inflammatory and oxidative stress parameters: favored the activity of 12/15-lipoxygenases on ω-3 PUFAs, enhanced glutathione peroxidases activity, modulated proinflammatory lipid mediators synthesis through the cyclooxygenase (COX) pathways and down-regulated the synthesis de novo of ARA leaded by Δ5 desaturase. Although polyphenols exerted an antioxidative and antiinflammatory effect in the standard diet, they were less effective to reduce inflammation in the HFHS dietary model. Contrary to the effect observed in the standard diet, polyphenols up-regulated COX pathways toward ω-6 proinflammatory eicosanoids as PGE 2 and 11-HETE and decreased the detoxification of ω-3 hydroperoxides in the HFHS diet. As a result, additive effects between fish oils and polyphenols were found in the standard diet in terms of reducing inflammation and oxidative stress. However, in the HFHS diets, fish oils seem to be the one responsible for the positive effects found in the combined group. Copyright © 2017 Elsevier Inc. All rights reserved.
Body weight affects ω-3 polyunsaturated fatty acid (PUFA) accumulation in youth following supplementation in post-hoc analyses of a randomized controlled trial.

PubMed

Christian, Lisa M; Young, Andrea S; Mitchell, Amanda M; Belury, Martha A; Gracious, Barbara L; Arnold, L Eugene; Fristad, Mary A

2017-01-01

Guidelines for suggested intake of ω-3 polyunsaturated fatty acids (PUFAs) are limited in youth and rely primarily on age. However, body weight varies considerably within age classifications. The current analyses examined effects of body weight and body mass index (BMI) on fatty acid accumulation in 64 youth (7-14 years) with a diagnosed mood disorder in a double-blind randomized-controlled trial (2000mg ω-3 supplements or a control capsule) across 12 weeks. Weight and height were measured at the first study visit and EPA and DHA levels were determined using fasting blood samples obtained at both the first and end-of-study visits. In the ω-3 supplementation group, higher baseline body weight predicted less plasma accumulation of both EPA [B = -0.047, (95% CI = -0.077; -0.017), β = -0.54, p = 0.003] and DHA [B = -0.02, (95% CI = -0.034; -0.007), β = -0.52, p = 0.004]. Similarly, higher BMI percentile as well as BMI category (underweight, normal weight, overweight/obese) predicted less accumulation of EPA and DHA (ps≤0.01). Adherence to supplementation was negatively correlated with BMI percentile [B = -0.002 (95% CI = -0.004; 0.00), β = -0.44, p = 0.019], but did not meaningfully affect observed associations. As intended, the control supplement exerted no significant effect on plasma levels of relevant fatty acids regardless of youth body parameters. These data show strong linear relationships of both absolute body weight and BMI percentile with ω-3 PUFA accumulation in youth. A dose-response effect was observed across the BMI spectrum. Given increasing variability in weight within BMI percentile ranges as youth age, dosing based on absolute weight should be considered. Moreover, effects of weight should be incorporated into statistical models in studies examining clinical effects of ω-3 PUFAs in youth as well as adults, as weight-related differences in effects may contribute meaningfully to inconsistencies in the current literature. WHO International
Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment

PubMed Central

Saunders, Erika FH; Reider, Aubrey; Singh, Gagan; Gelenberg, Alan J; Rapoport, Stanley I

2015-01-01

Objectives Omega (n)-3 and n-6 polyunsaturated fatty acids (PUFA) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n-3 PUFA would be lower and of n-6 PUFA higher in subjects with bipolar disorder (BD) compared to healthy controls (HC), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n-3 but lower n-6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids. Methods This observational, parallel group study compared biomarkers between HC (n = 31), and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow-up). Plasma concentrations of five PUFA [linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], of two saturated fatty acids (palmitic acid and stearic acid) and of two monounsaturated fatty acids (palmitoleic acid, oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFA, ratios of n-3 PUFA (DHA:ALA, EPA:ALA, EPA:DHA), and the ratio of n-6:n-3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t-tests, between the BD group at baseline and follow-up using paired t-tests. Comparison of categorical variables was performed using Chi-square tests. Pearson’s r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis. Results UE EPA was lower in BD than HC, with a large effect size (Cohen’s d = 0.86, p < 0.002), however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between BD and HC after Bonferroni correction for 40
Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids

USDA-ARS?s Scientific Manuscript database

The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 PUFA is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and dependent on cholesterol status. To further elucidate the mechanism(...
ω-3 Fatty acids for major depressive disorder in adults: an abridged Cochrane review

PubMed Central

Appleton, Katherine M; Sallis, Hannah M; Perry, Rachel; Ness, Andrew R; Churchill, Rachel

2016-01-01

Objective To assess the effects of n-3 polyunsaturated fatty acids (n-3PUFAs; also known as ω-3 fatty acids) compared with comparator for major depressive disorder (MDD) in adults. Design Systematic review and meta-analyses. Data sources The Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Registers (CCDANCTR) and International Trial Registries searched to May 2015. CINAHL searched to September 2013. Trial selection Inclusion criteria: a randomised controlled trial (RCT); that provided n-3PUFAs as an intervention; used a comparator; measured depressive symptomology as an outcome; and was conducted in adults with MDD. Outcomes Primary outcomes were depressive symptomology and adverse events. Results 20 trials encompassing 26 relevant studies were found. For n-3PUFAs versus placebo, n-3PUFA supplementation resulted in a small-to-modest benefit for depressive symptomology: SMD=−0.32 (95% CI −0.52 to −0.12; 25 studies, 1373 participants, very low-quality evidence), but this effect is unlikely to be clinically meaningful, is very imprecise and, based on funnel plot inspection, sensitivity analyses and comparison with large well-conducted trials, is likely to be biased. Considerable evidence of heterogeneity between studies was also found, and was not explained by subgroup or sensitivity analyses. Numbers of individuals experiencing adverse events were similar in intervention and placebo groups (OR=1.24, 95% CI 0.95 to 1.62; 19 studies, 1207 participants; very low-quality evidence). For n-3PUFAs versus antidepressants, no differences were found between treatments in depressive symptomology (MD=−0.70 (95% CI −5.88 to 4.48); 1 study, 40 participants, very low-quality evidence). Conclusions At present, we do not have sufficient evidence to determine the effects of n-3PUFAs as a treatment for MDD. Further research in the form of adequately powered RCTs is needed. PMID:26936905
Omega-3 Polyunsaturated Fatty Acids and Oxylipins in Neuroinflammation and Management of Alzheimer Disease.

PubMed

Devassy, Jessay Gopuran; Leng, Shan; Gabbs, Melissa; Monirujjaman, Md; Aukema, Harold M

2016-09-01

Alzheimer disease (AD) is becoming one of the most prevalent neurodegenerative conditions worldwide. Although the disease progression is becoming better understood, current medical interventions can only ameliorate some of the symptoms but cannot slow disease progression. Neuroinflammation plays an important role in the advancement of this disorder, and n-3 (ω-3) polyunsaturated fatty acids (PUFAs) are involved in both the reduction in and resolution of inflammation. These effects may be mediated by the anti-inflammatory and proresolving effects of bioactive lipid mediators (oxylipins) derived from n-3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in fish oil. Although interventions have generally used fish oil containing both EPA and DHA, several studies that used either EPA or DHA alone or specific oxylipins derived from these fatty acids indicate that they have distinct effects. Both DHA and EPA can reduce neuroinflammation and cognitive decline, but EPA positively influences mood disorders, whereas DHA maintains normal brain structure. Fewer studies with a plant-derived n-3 PUFA, α-linolenic acid, suggest that other n-3 PUFAs and their oxylipins also may positively affect AD. Further research identifying the unique anti-inflammatory and proresolving properties of oxylipins from individual n-3 PUFAs will enable the discovery of novel disease-management strategies in AD. © 2016 American Society for Nutrition.
Low levels of serum n-3 polyunsaturated fatty acids are associated with worse heart failure-free survival in patients after acute myocardial infarction.

PubMed

Hara, Masahiko; Sakata, Yasuhiko; Nakatani, Daisaku; Suna, Shinichiro; Usami, Masaya; Matsumoto, Sen; Hamasaki, Toshimitsu; Doi, Yasuji; Nishino, Masami; Sato, Hiroshi; Kitamura, Tetsuhisa; Nanto, Shinsuke; Hori, Masatsugu; Komuro, Issei

2013-01-01

Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associated with a lower risk of atherosclerotic cardiovascular events, particularly acute myocardial infarction (AMI). However, limited data are available regarding the association between serum n-3 PUFA levels and heart failure (HF) events in survivors of AMI. We evaluated whether serum DHA and EPA levels were associated with HF-free survival and HF hospitalization rates after AMI. A total of 712 patients were divided into 3 groups according to their tertile serum levels of DHA and EPA (Low, Middle, and High). Propensity-score-stratified Cox regression analysis revealed that DHA- and EPA-Low groups presented statistically significant worse HF-free survival (hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.03-2.72, P=0.0358, and HR 1.69, 95% CI 1.05-2.72, P=0.0280, respectively), with the EPA-Low group having a higher risk of HF hospitalization (HR 2.40, 95% CI 1.21-4.75, P=0.0097) than the DHA-Low group (HR 1.72, 95% CI 0.86-3.45, P=0.1224). The relationship between a low DHA or EPA level and decreased HF-free survival was almost common to all subgroups; however, the effect of low serum EPA on HF hospitalization was prominent in male patients, and those with low levels of high-density lipoprotein cholesterol or without statin therapy. Low levels of circulating n-3 PUFA are associated with decreased HF-free survival in post-AMI patients.
Lower inter-partum interval and unhealthy life-style factors are inversely associated with n-3 essential fatty acids changes during pregnancy: a prospective cohort with Brazilian women.

PubMed

Pinto, Thatiana J P; Farias, Dayana R; Rebelo, Fernanda; Lepsch, Jaqueline; Vaz, Juliana S; Moreira, Júlia D; Cunha, Geraldo M; Kac, Gilberto

2015-01-01

To analyze serum fatty acids concentrations during healthy pregnancy and evaluate whether socioeconomic, demographic, obstetric, nutritional, anthropometric and lifestyle factors are associated with their longitudinal changes. A prospective cohort of 225 pregnant women was followed in the 5th-13th, 20th-26th and 30th-36th weeks of gestation. Serum samples were collected in each trimester of pregnancy and analyzed to determine the fatty acids composition using a high-throughput robotic direct methylation method coupled with fast gas-liquid chromatography. The independent variables comprised the subjects' socioeconomic and demographic status, obstetric history, early pregnancy body mass index (BMI), dietary and lifestyle parameters. Analyses were performed using linear mixed-effects models. The overall absolute concentrations of fatty acids increased from the 1st to the 2nd trimester and slightly increased from the 2nd to the 3rd trimester. Early pregnancy BMI, inter-partum interval and weekly fish intake were the factors associated with changes in eicosapentaenoic + docosahexaenoic acids (EPA+DHA) and total n-3 polyunsaturated fatty acids (PUFAs). Early pregnancy BMI, age and monthly per-capita income were inversely associated with the changes in the n-6/n-3 ratio. Alcohol consumption was positively associated with the n-6/n-3 ratio. Early pregnancy BMI was positively associated with EPA+DHA and total n-3 PUFAs, while presenting a reduced weekly fish intake and a lower inter-partum interval were associated with lower levels of n-3 PUFAs. A lower per-capita family income and a drinking habit were factors that were positively associated with a higher n-6/n-3 ratio.

Neuroinflammation in Autism: Plausible Role of Maternal Inflammation, Dietary Omega 3, and Microbiota

PubMed Central

Madore, Charlotte; Leyrolle, Quentin; Lacabanne, Chloé; Benmamar-Badel, Anouk; Joffre, Corinne; Nadjar, Agnes

2016-01-01

Several genetic causes of autism spectrum disorder (ASD) have been identified. However, more recent work has highlighted that certain environmental exposures early in life may also account for some cases of autism. Environmental insults during pregnancy, such as infection or malnutrition, seem to dramatically impact brain development. Maternal viral or bacterial infections have been characterized as disruptors of brain shaping, even if their underlying mechanisms are not yet fully understood. Poor nutritional diversity, as well as nutrient deficiency, is strongly associated with neurodevelopmental disorders in children. For instance, imbalanced levels of essential fatty acids, and especially polyunsaturated fatty acids (PUFAs), are observed in patients with ASD and other neurodevelopmental disorders (e.g., attention deficit hyperactivity disorder (ADHD) and schizophrenia). Interestingly, PUFAs, and specifically n-3 PUFAs, are powerful immunomodulators that exert anti-inflammatory properties. These prenatal dietary and immunologic factors not only impact the fetal brain, but also affect the microbiota. Recent work suggests that the microbiota could be the missing link between environmental insults in prenatal life and future neurodevelopmental disorders. As both nutrition and inflammation can massively affect the microbiota, we discuss here how understanding the crosstalk between these three actors could provide a promising framework to better elucidate ASD etiology. PMID:27840741
Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies.

PubMed

Luchtman, Dirk W; Song, Cai

2013-01-01

Omega-(n)-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are major components of neuronal membranes and have a wide range of functions, from modulating synaptic plasticity and neurochemistry, to neuroimmune-modulation and neuroprotection. Thus, it is not surprising that n-3 PUFA are widely acknowledged to have cognitive-enhancing effects. Although clinical evidence is somewhat conflicting, probably in large part due to methodological issues, animal studies have consistently demonstrated that n-3 PUFA are indispensable for proper brain development, may enhance cognitive function in healthy, adult individuals and attenuate cognitive impairment in aging and age-related disorders, such as dementia. This review discusses and integrates up to date evidence from clinical and animal studies investigating the cognitive-enhancing effects of n-3 PUFA during development, child- and adult-hood, as well as old-age with associated neurodegenerative diseases, such as Alzheimer's disease. Furthermore, we cover the major underlying biochemical and neurophysiological mechanisms by which n-3 PUFA mediate these effects on cognition. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.
Perinatal supplementation with omega-3 polyunsaturated fatty acids improves sevoflurane-induced neurodegeneration and memory impairment in neonatal rats.

PubMed

Lei, Xi; Zhang, Wenting; Liu, Tengyuan; Xiao, Hongyan; Liang, Weimin; Xia, Weiliang; Zhang, Jun

2013-01-01

To investigate if perinatal Omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation can improve sevoflurane-induced neurotoxicity and cognitive impairment in neonatal rats. Female Sprague-Dawley rats (n = 3 each group) were treated with or without an n-3 PUFAs (fish oil) enriched diet from the second day of pregnancy to 14 days after parturition. The offspring rats (P7) were treated with six hours sevoflurane administration (one group without sevoflurane/prenatal n-3 PUFAs supplement as control). The 5-bromodeoxyuridine (Brdu) was injected intraperitoneally during and after sevoflurane anesthesia to assess dentate gyrus (DG) progenitor proliferation. Brain tissues were harvested and subjected to Western blot and immunohistochemistry respectively. Morris water maze spatial reference memory, fear conditioning, and Morris water maze memory consolidation were tested at P35, P63 and P70 (n = 9), respectively. Six hours 3% sevoflurane administration increased the cleaved caspase-3 in the thalamus, parietal cortex but not hippocampus of neonatal rat brain. Sevoflurane anesthesia also decreased the neuronal precursor proliferation of DG in rat hippocampus. However, perinatal n-3 PUFAs supplement could decrease the cleaved caspase-3 in the cerebral cortex of neonatal rats, and mitigate the decrease in neuronal proliferation in their hippocampus. In neurobehavioral studies, compared with control and n-3 PUFAs supplement groups, we did not find significant spatial cognitive deficit and early long-term memory impairment in sevoflurane anesthetized neonatal rats at their adulthood. However, sevoflurane could impair the immediate fear response and working memory and short-term memory. And n-3 PUFAs could improve neurocognitive function in later life after neonatal sevoflurane exposure. Our study demonstrated that neonatal exposure to prolonged sevoflurane could impair the immediate fear response, working memory and short-term memory of rats at their adulthood
Omega-3 Polyunsaturated Fatty Acids Enriched Hen Eggs Consumption Enhances Microvascular Reactivity in Young Healthy Individuals.

PubMed

Stupin, Ana; Rasic, Lidija; Matic, Anita; Stupin, Marko; Kralik, Zlata; Kralik, Gordana; Grcevic, Manuela; Drenjancevic, Ines

2018-04-10

Whilst the beneficial effect of omega-3 polyunsaturated fatty acids (PUFAs) supplementation on cardiovascular (CV) system is well supported in CV patients, the effect of consumption of omega-3 PUFAs enriched functional food in healthy individuals is still not fully elucidated. This study aimed to determine the effect of consumption of omega-3 PUFAs enriched hen eggs on microvascular reactivity (primary outcome), blood pressure (BP) and serum lipid profile in young healthy individuals. Control group (N=16) ate three ordinary hen eggs (277 mg omega-3 PUFAs/day), and OMEGA-3 group (N=20) ate three omega-3 PUFAs enriched eggs containing 259 mg of omega-3 PUFAs/egg daily (ALA 167 mg/egg, EPA 7 mg/egg, DHA 84 mg/egg) for 3 weeks (777 mg omega-3 PUFAs/day). Post-occlusive reactive hyperemia (PORH) in skin microcirculation assessed by laser Doppler flowmetry, serum lipid profile, fasting blood glucose, high-sensitivity C-reactive protein (hsCRP) and arterial BP were measured in all subjects before and after the protocol. PORH was significantly enhanced, and triglycerides, hsCRP and BP were significantly decreased in OMEGA-3 group compared to baseline measurement, while there was no significant difference in Control group after the protocol compared to baseline. This is the first study to demonstrate that consumption of a mixture of omega-3 PUFAs (ALA+EPA+DHA), provided via enriched hen eggs, elicits changes in microvascular reactivity, BP and triglycerides level in healthy subjects that are associated with CV benefits, thus suggesting that daily consumption of omega-3 PUFAs enriched eggs in healthy individuals may potentially contribute to CV risk factors attenuation and disease prevention.
Influence of maternal and socioeconomic factors on breast milk fatty acid composition in urban, low‐income families

PubMed Central

Nayak, Uma; Kanungo, Suman; Zhang, Dadong; Ross Colgate, E.; Carmolli, Marya P.; Dey, Ayan; Alam, Masud; Manna, Byomkesh; Nandy, Ranjan Kumar; Kim, Deok Ryun; Paul, Dilip Kumar; Choudhury, Saugato; Sahoo, Sushama; Harris, William S.; Wierzba, Thomas F.; Ahmed, Tahmeed; Kirkpatrick, Beth D.; Haque, Rashidul; Petri, William A.

2017-01-01

Abstract The lipid composition of breast milk may have a significant impact on early infant growth and cognitive development. Comprehensive breast milk data is lacking from low‐income populations in the Indian subcontinent impeding assessment of deficiencies and limiting development of maternal nutritional interventions. A single breast milk specimen was collected within 6 weeks postpartum from two low‐income maternal cohorts of exclusively breastfed infants, from Dhaka, Bangladesh (n = 683) and Kolkata, India (n = 372) and assayed for percentage composition of 26 fatty acids. Mature milk (>15 days) in Dhaka (n = 99) compared to Kolkata (n = 372) was higher in total saturated fatty acid (SFA; mean 48% vs. 44%) and disproportionately lower in ω3‐polyunsaturated fatty acid (PUFA), hence the ω6‐ and ω3‐PUFA ratio in Dhaka were almost double the value in Kolkata. In both sites, after adjusting for days of lactation, increased maternal education was associated with decreased SFA and PUFA, and increasing birth order or total pregnancies was associated with decreasing ω6‐PUFA or ω3‐PUFA by a factor of 0.95 for each birth and pregnancy. In Dhaka, household prosperity was associated with decreased SFA and PUFA and increased ω6‐ and ω3‐PUFA. Maternal height was associated with increased SFA and PUFA in Kolkata (1% increase per 1 cm), but body mass index showed no independent association with either ratio in either cohort. In summary, the socioeconomic factors of maternal education and household prosperity were associated with breast milk composition, although prosperity may only be important in higher cost of living communities. Associated maternal biological factors were height and infant birth order, but not adiposity. Further study is needed to elucidate the underlying mechanisms of these effects. PMID:28198164
Influence of maternal and socioeconomic factors on breast milk fatty acid composition in urban, low-income families.

PubMed

Nayak, Uma; Kanungo, Suman; Zhang, Dadong; Ross Colgate, E; Carmolli, Marya P; Dey, Ayan; Alam, Masud; Manna, Byomkesh; Nandy, Ranjan Kumar; Kim, Deok Ryun; Paul, Dilip Kumar; Choudhury, Saugato; Sahoo, Sushama; Harris, William S; Wierzba, Thomas F; Ahmed, Tahmeed; Kirkpatrick, Beth D; Haque, Rashidul; Petri, William A; Mychaleckyj, Josyf C

2017-10-01

The lipid composition of breast milk may have a significant impact on early infant growth and cognitive development. Comprehensive breast milk data is lacking from low-income populations in the Indian subcontinent impeding assessment of deficiencies and limiting development of maternal nutritional interventions. A single breast milk specimen was collected within 6 weeks postpartum from two low-income maternal cohorts of exclusively breastfed infants, from Dhaka, Bangladesh (n = 683) and Kolkata, India (n = 372) and assayed for percentage composition of 26 fatty acids. Mature milk (>15 days) in Dhaka (n = 99) compared to Kolkata (n = 372) was higher in total saturated fatty acid (SFA; mean 48% vs. 44%) and disproportionately lower in ω3-polyunsaturated fatty acid (PUFA), hence the ω6- and ω3-PUFA ratio in Dhaka were almost double the value in Kolkata. In both sites, after adjusting for days of lactation, increased maternal education was associated with decreased SFA and PUFA, and increasing birth order or total pregnancies was associated with decreasing ω6-PUFA or ω3-PUFA by a factor of 0.95 for each birth and pregnancy. In Dhaka, household prosperity was associated with decreased SFA and PUFA and increased ω6- and ω3-PUFA. Maternal height was associated with increased SFA and PUFA in Kolkata (1% increase per 1 cm), but body mass index showed no independent association with either ratio in either cohort. In summary, the socioeconomic factors of maternal education and household prosperity were associated with breast milk composition, although prosperity may only be important in higher cost of living communities. Associated maternal biological factors were height and infant birth order, but not adiposity. Further study is needed to elucidate the underlying mechanisms of these effects. © 2017 The Authors. Maternal & Child Nutrition Published by John Wiley & Sons Ltd.
Clinical consequences of untreated dental caries assessed using PUFA index and its covariates in children residing in orphanages of Pakistan.

PubMed

Kamran, Ramsha; Farooq, Warda; Faisal, Mehreen Riaz; Jahangir, Faisal

2017-07-11

The purpose of this study was to determine the prevalence and clinical effects of untreated dental caries in Pakistani children residing in orphanages using the DMFT and PUFA index; association of decay and untreated dental caries with demographics including type of orphanage; behavioural and dental visiting pattern; and association of dental pain experience and type of orphanage with dental visiting. A cross-sectional survey was conducted on a total of 753 orphan children belonging to 4-17 years of age group residing in twin cities of Rawalpindi and Islamabad, Pakistan. Clinical examination of children was performed using the DMFT and PUFA index for the assessment of dental caries and untreated decay, followed by questionnaire enquiring about eating and oral hygiene habits, dental visiting pattern and dental pain and swelling experience. Association between dental decay, child's dental visiting and pain as a consequence of untreated decay was carried out using chi square test and logistic regression analysis. The overall caries prevalence was 34.8% and overall prevalence of PUFA/pufa was 15.9%. The mean score of DMFT and dmft was 1.18 (SD 0.39) and 1.04 (SD 0.23), and mean PUFA was 1.18 (SD 0.57) and mean pufa score 1.14 (SD 0.35). Untreated caries ratio was found to be 49.1% indicating half the decay had progressed to involve the pulp. No significant association of gender was found with DMFT, dmft, PUFA and pufa (p > 0.05), however, when analysed individually, the 'D' component of DMFT was significantly associated with male gender (p = 0.05). Furthermore, no significant association of DMFT/dmft or PUFA/pufa in either dentition was found with behavioural characteristics such as dietary and oral hygiene habits. Also, 66.2% children who experienced pain had not been to the dentist in the past year (p = 0.013) and 52.6% children who mentioned experiencing pain at night had not been to the dentist in the past year (p = 0.009). Children with decay were more
Genetics Home Reference: N-acetylglutamate synthase deficiency

MedlinePlus

... Hyperammonemia due to N-acetylglutamate synthase deficiency Screening, Technology and Research in Genetics Patient Support and Advocacy Resources (4 links) Children Living with Inherited Metabolic Diseases National Organization for ...
Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1.

PubMed

Zhang, Meijuan; Wang, Suping; Mao, Leilei; Leak, Rehana K; Shi, Yejie; Zhang, Wenting; Hu, Xiaoming; Sun, Baoliang; Cao, Guodong; Gao, Yanqin; Xu, Yun; Chen, Jun; Zhang, Feng

2014-01-29

Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies.
Blood pressure-lowering effects of long chain n-3 fatty acids from meals enriched with liquid fish oil and from microencapsulated powder.

PubMed

Sveinsdottir, Kolbrun; Martinsdottir, Emilia; Ramel, Alfons

2016-12-01

Diet plays an important role in the etiology of hypertension. Blood pressure (BP)-lowering properties of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) are promising. The aim was to investigate whether different formulations of fish oil differently affect blood pressure in community-dwelling adults. The hypothesis was that fish oil formulations would improve BP in comparison with a placebo. In this 4-week randomized, placebo-controlled, doubly-blinded dietary intervention study, participants (N = 99, >50 years) from the capital area of Iceland were randomized into three groups. Group 1 (n = 38) received 6 meals/week fortified with a liquid fish oil and placebo powder. Group 2 (n = 30) received conventional (unfortified) meals and microencapsulated powder. Group 3 (n = 31) was the control group which received conventional meals and placebo powder. Calculated on a weekly basis, the amount of EPA + DHA provided was 1.5 g/d. Systolic (SBP) and diastolic BP (DBP) were measured before and after the intervention period. Seventy-seven subjects finished the study (77.8%). Drop-out rates were not different between groups. According to multivariate statistics, endpoint SBP was lower in Group 1 (-7.0 mmHg, p = 0.037) and in Group 2 (-7.2 mmHg, p = 0.037) as compared with Group 3. There was no significant difference in DBP between the groups. Our study shows that LC n-3 PUFA from microencapsulated powder are equally effective to meaningfully reduce SBP as LC n-3 PUFA from meals enriched with liquid fish oil in comparison with a control group.
Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment.

PubMed

Saunders, Erika Fh; Reider, Aubrey; Singh, Gagan; Gelenberg, Alan J; Rapoport, Stanley I

2015-11-01

Omega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n-3 PUFAs would be lower and those of n-6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n-3 but lower n-6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids. This observational, parallel group study compared biomarkers between HCs (n = 31) and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow-up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n-3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n-6:n-3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t-tests, and between the BD group at baseline and follow-up using paired t-tests. Comparison of categorical variables was performed using chi-square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis. UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d = 0.86, p < 0.002); however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between the BD and HC groups after Bonferroni correction
Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial.

PubMed

Sinn, Natalie; Milte, Catherine M; Street, Steven J; Buckley, Jonathan D; Coates, Alison M; Petkov, John; Howe, Peter R C

2012-06-01

Depressive symptoms may increase the risk of progressing from mild cognitive impairment (MCI) to dementia. Consumption of n-3 PUFA may alleviate both cognitive decline and depression. The aim of the present study was to investigate the benefits of supplementing a diet with n-3 PUFA, DHA and EPA, for depressive symptoms, quality of life (QOL) and cognition in elderly people with MCI. We conducted a 6-month double-blind, randomised controlled trial. A total of fifty people aged >65 years with MCI were allocated to receive a supplement rich in EPA (1·67 g EPA + 0·16 g DHA/d; n 17), DHA (1·55 g DHA + 0·40 g EPA/d; n 18) or the n-6 PUFA linoleic acid (LA; 2·2 g/d; n 15). Treatment allocation was by minimisation based on age, sex and depressive symptoms (Geriatric Depression Scale, GDS). Physiological and cognitive assessments, questionnaires and fatty acid composition of erythrocytes were obtained at baseline and 6 months (completers: n 40; EPA n 13, DHA n 16, LA n 11). Compared with the LA group, GDS scores improved in the EPA (P=0·04) and DHA (P=0·01) groups and verbal fluency (Initial Letter Fluency) in the DHA group (P=0·04). Improved GDS scores were correlated with increased DHA plus EPA (r 0·39, P=0·02). Improved self-reported physical health was associated with increased DHA. There were no treatment effects on other cognitive or QOL parameters. Increased intakes of DHA and EPA benefited mental health in older people with MCI. Increasing n-3 PUFA intakes may reduce depressive symptoms and the risk of progressing to dementia. This needs to be investigated in larger, depressed samples with MCI.
The Fast Spiral-SelMQC Technique for In Vivo MR Spectroscopic Imaging of Polyunsaturated Fatty Acids (PUFA) in Human Breast Tissue‡

PubMed Central

Zhu, He; Rubin, Denis; He, Qiuhong

2011-01-01

The Selective Multiple-Quantum Coherence Transfer (Sel-MQC) method has been applied to image polyunsaturated fatty acids (PUFA) distributions in human breast tissues in vivo for cancer detection, with complete suppression of the unwanted lipid and water signals in a single scan. The Cartesian k-space mapping of PUFA in vivo using the Sel-MQC CSI technique, however, requires excessive MR scan time. In this article, we report a fast Spiral-SelMQC sequence employing a rapid spiral k-space sampling scheme. The Spiral-SelMQC images of PUFA distribution in human breast were acquired using two-interleaved spirals on a 3T GE Signa MRI scanner. Approximately 160-fold reduction of acquisition time was observed as compared to the corresponding Sel-MQC CSI method with an equivalent number of scans, permitting acquisition of high-resolution PUFA images in minutes. The reconstructed Spiral-SelMQC PUFA images of human breast tissues achieved a sub-millimeter resolution of 0.54×0.54 or 0.63×0.63mm2/pixel for FOV = 14 or 16cm, respectively. The Spiral-SelMQC parameters for PUFA detection were optimized in 2D Sel-MQC experiments to suppress monounsaturated fatty acids (MUFA) and other lipid signals. The fast in vivo Spiral-SelMQC imaging method will be applied to study human breast cancer and other human diseases in extracranial organs. PMID:22028250
(n-3) Fatty Acids Alleviate Adipose Tissue Inflammation and Insulin Resistance: Mechanistic Insights12

PubMed Central

Kalupahana, Nishan S.; Claycombe, Kate J.; Moustaid-Moussa, Naima

2011-01-01

Obesity is associated with the metabolic syndrome, a significant risk factor for developing type 2 diabetes and cardiovascular diseases. Chronic low-grade inflammation occurring in the adipose tissue of obese individuals is causally linked to the pathogenesis of insulin resistance and the metabolic syndrome. Although the exact trigger of this inflammatory process is unknown, adipose tissue hypoxia, endoplasmic reticular stress, and saturated fatty acid–mediated activation of innate immune processes have been identified as important processes in these disorders. Furthermore, macrophages and T lymphocytes have important roles in orchestrating this immune process. Although energy restriction leading to weight loss is the primary dietary intervention to reverse these obesity-associated metabolic disorders, other interventions targeted at alleviating adipose tissue inflammation have not been explored in detail. In this regard, (n-3) PUFA of marine origin both prevent and reverse high-fat-diet–induced adipose tissue inflammation and insulin resistance in rodents. We provide an update on the pathogenesis of adipose tissue inflammation and insulin resistance in obesity and discuss potential mechanisms by which (n-3) PUFA prevent and reverse these changes and the implications in human health. PMID:22332072
Omega-3 and Omega-6 Polyunsaturated Fatty Acid Levels and Correlations with Symptoms in Children with Attention Deficit Hyperactivity Disorder, Autistic Spectrum Disorder and Typically Developing Controls

PubMed Central

Niyonsenga, Theophile; Duff, Jacques

2016-01-01

Background There is evidence that children with Attention Deficit Hyperactivity Disorder (ADHD) and Autistic Spectrum Disorder (ASD) have lower omega-3 polyunsaturated fatty acid (n-3 PUFA) levels compared with controls and conflicting evidence regarding omega-6 (n-6) PUFA levels. Objectives This study investigated whether erythrocyte n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were lower and n-6 PUFA arachidonic acid (AA) higher in children with ADHD, ASD and controls, and whether lower n-3 and higher n-6 PUFAs correlated with poorer scores on the Australian Twin Behaviour Rating Scale (ATBRS; ADHD symptoms) and Test of Variable Attention (TOVA) in children with ADHD, and Childhood Autism Rating Scale (CARS) in children with ASD. Methods Assessments and blood samples of 565 children aged 3–17 years with ADHD (n = 401), ASD (n = 85) or controls (n = 79) were analysed. One-way ANOVAs with Tukey’s post-hoc analysis investigated differences in PUFA levels between groups and Pearson’s correlations investigated correlations between PUFA levels and ATBRS, TOVA and CARS scores. Results Children with ADHD and ASD had lower DHA, EPA and AA, higher AA/EPA ratio and lower n-3/n-6 than controls (P<0.001 except AA between ADHD and controls: P = 0.047). Children with ASD had lower DHA, EPA and AA than children with ADHD (P<0.001 for all comparisons). ATBRS scores correlated negatively with EPA (r = -.294, P<0.001), DHA (r = -.424, P<0.001), n-3/n-6 (r = -.477, P<0.001) and positively with AA/EPA (r = .222, P <.01). TOVA scores correlated positively with DHA (r = .610, P<0.001), EPA (r = .418, P<0.001) AA (r = .199, P<0.001), and n-3/n-6 (r = .509, P<0.001) and negatively with AA/EPA (r = -.243, P<0.001). CARS scores correlated significantly with DHA (r = .328, P = 0.002), EPA (r = -.225, P = 0.038) and AA (r = .251, P = 0.021). Conclusions Children with ADHD and ASD had low levels of EPA, DHA and AA and high ratio of n-6/n-3 PUFAs and these
Omega-3 and Omega-6 Polyunsaturated Fatty Acid Levels and Correlations with Symptoms in Children with Attention Deficit Hyperactivity Disorder, Autistic Spectrum Disorder and Typically Developing Controls.

PubMed

Parletta, Natalie; Niyonsenga, Theophile; Duff, Jacques

2016-01-01

There is evidence that children with Attention Deficit Hyperactivity Disorder (ADHD) and Autistic Spectrum Disorder (ASD) have lower omega-3 polyunsaturated fatty acid (n-3 PUFA) levels compared with controls and conflicting evidence regarding omega-6 (n-6) PUFA levels. This study investigated whether erythrocyte n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were lower and n-6 PUFA arachidonic acid (AA) higher in children with ADHD, ASD and controls, and whether lower n-3 and higher n-6 PUFAs correlated with poorer scores on the Australian Twin Behaviour Rating Scale (ATBRS; ADHD symptoms) and Test of Variable Attention (TOVA) in children with ADHD, and Childhood Autism Rating Scale (CARS) in children with ASD. Assessments and blood samples of 565 children aged 3-17 years with ADHD (n = 401), ASD (n = 85) or controls (n = 79) were analysed. One-way ANOVAs with Tukey's post-hoc analysis investigated differences in PUFA levels between groups and Pearson's correlations investigated correlations between PUFA levels and ATBRS, TOVA and CARS scores. Children with ADHD and ASD had lower DHA, EPA and AA, higher AA/EPA ratio and lower n-3/n-6 than controls (P<0.001 except AA between ADHD and controls: P = 0.047). Children with ASD had lower DHA, EPA and AA than children with ADHD (P<0.001 for all comparisons). ATBRS scores correlated negatively with EPA (r = -.294, P<0.001), DHA (r = -.424, P<0.001), n-3/n-6 (r = -.477, P<0.001) and positively with AA/EPA (r = .222, P <.01). TOVA scores correlated positively with DHA (r = .610, P<0.001), EPA (r = .418, P<0.001) AA (r = .199, P<0.001), and n-3/n-6 (r = .509, P<0.001) and negatively with AA/EPA (r = -.243, P<0.001). CARS scores correlated significantly with DHA (r = .328, P = 0.002), EPA (r = -.225, P = 0.038) and AA (r = .251, P = 0.021). Children with ADHD and ASD had low levels of EPA, DHA and AA and high ratio of n-6/n-3 PUFAs and these correlated significantly with symptoms. Future research should
Inhibition of neuroblastoma cell proliferation with omega-3 fatty acids and treatment of a murine model of human neuroblastoma using a diet enriched with omega-3 fatty acids in combination with sunitinib.

PubMed

Barnés, Carmen M; Prox, Daniela; Christison-Lagay, Emily A; Le, Hau D; Short, Sarah; Cassiola, Flavia; Panigrahy, Dipak; Chaponis, Deviney; Butterfield, Catherine; Nehra, Deepika; Fallon, Erica M; Kieran, Mark; Folkman, Judah; Puder, Mark

2012-02-01

We investigated the use of dietary omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) in the treatment of neuroblastoma both as a sole agent and in combination with sunitinib, a broad-spectrum tyrosine kinase receptor inhibitor. Substitution of all dietary fat with menhaden oil (ω-3 PUFA rich) resulted in a 40-70% inhibition of tumor growth and a statistically significant difference in the levels of several PUFAs (18:2 ω-6, 20:4 ω-6, 22:4 ω-6, 20:5 ω-3) as compared with a control diet. Furthermore, tumors from animals on the ω-3 fatty acid (FA)-enriched diet had an elevated triene/tetraene ratio suggestive of a change in local eicosanoid metabolism in these tissues similar to that seen with essential fatty acid deficiency. The ω-3 FA-enriched diet also decreased tumor-associated inflammatory cells and induced mitochondrial changes suggestive of mitochondrial damage. Combination treatment with sunitinib resulted in further reduction in tumor proliferation and microvessel density. These findings suggest a potential role for ω-3 PUFAs in the combination treatment of neuroblastoma. We used a murine model of orthotopic and subcutaneous human neuroblastoma and diets that differ in the FA content to define the optimal dietary ω-3/omega-6 (ω-6) FA ratio required for the inhibition of these tumors.
Omega 3 and omega 6 fatty acids in human and animal health: an African perspective.

PubMed

Dunbar, B S; Bosire, R V; Deckelbaum, R J

2014-12-01

Lipids are essential for plant and animal development, growth and nutrition and play critical roles in health and reproduction. The dramatic increase in the human population has put increasing pressure on human food sources, especially of those sources of food which contain adequate levels of polyunsaturated fatty acids (PUFAs) and more importantly, sources of food which have favorable ratios of the n-3 (18-carbon, α-linolenic acid, ALA) to n-6 (18-carbon linoleic acid, LA) PUFAs. Recent studies have demonstrated the beneficial effects of the n-3 PUFAs in diets as well as potentially negative effects of excessive levels of n-6 PUFAs in diets. This review discusses these human health issues relating to changes in diets based on environmental and industrial changes as well as strategies in East Africa for improving lipid composition of food using indigenous sources. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Role of PUFAs, the precursors of endocannabinoids, in human obesity and type 2 diabetes.

PubMed

Dain, Alejandro; Repossi, Gaston; Das, Undurti N; Eynard, Aldo Renato

2010-06-01

Polyunsaturated fatty acids (PUFAs) serve as precursors of the endocannabinoids (ECs) that are bioactive lipids molecules. Recent studies revealed that ECs participate in several physiological and pathological processes including obesity and type 2 diabetes mellitus. Here we review the experimental and clinical aspects of the role of endocannabinoids in obesity and type 2 diabetes mellitus and the modification of the endocannabinoids by exogenously administered PUFAs. Based on these evidences, we propose that the endocannabinoid system (ECS) can be modulated by exogenous manipulation of PUFAs that could help in the prevention and management of human diseases such as obesity, metabolic syndrome and type 2 diabetes mellitus.
Correlates of whole-blood polyunsaturated fatty acids among young children with moderate acute malnutrition.

PubMed

Yaméogo, C W; Cichon, B; Fabiansen, C; Rytter, M J H; Faurholt-Jepsen, D; Stark, K D; Briend, A; Shepherd, S; Traoré, A S; Christensen, V B; Michaelsen, K F; Friis, H; Lauritzen, L

2017-07-13

Severe acute malnutrition (SAM) has been associated with low polyunsaturated fatty acid (PUFA) status. However, investigations regarding PUFA status and correlates in children with moderate acute malnutrition (MAM) from low-income countries are scarce. The aim of this study was to describe whole-blood PUFA levels in children with moderate acute malnutrition (MAM) and to identify correlates of PUFAs. We conducted a cross-sectional study using baseline data from a prospective nutritional intervention trial among 1609 children with MAM aged 6-23 months in Burkina Faso,West Africa. Whole-blood PUFAs were measured by gas chromatography and expressed as percent of total whole-blood fatty acids (FA%). Potential correlates of PUFAs including infection, inflammation, hemoglobin, anthropometry (difference between children diagnosed as having MAM based on low mid-upper-arm-circumference (MUAC) only, low MUAC and weight-for-height z-score (WHZ), or low WHZ only) and diet were assessed by linear regression adjusted for age and sex. Children with MAM had low concentrations of whole-blood PUFAs, particularly n-3 PUFAs. Moreover, children diagnosed with MAM based only on low MUAC had 0.32 (95% confidence interval (CI), 0.14; 0.50) and 0.40 (95% CI, 0.16; 0.63) FA% lower arachidonic acid (AA) than those recruited based on both low WHZ as well as low MUAC and those recruited with low WHZ only, respectively. Infection and inflammation were associated with low levels of all long-chain (LC)-PUFAs, while hemoglobin was positively associated with whole-blood LC-PUFAs. While PUFA deficiency was not a general problem, overall whole-blood PUFA concentrations, especially of n-3 PUFAs, were low. Infection, inflammation, hemoglobin, anthropometry and diet were correlates of PUFAs concentrations in children with MAM. The trial is registered at http://www.isrctn.com ( ISRCTN42569496 ).

Purification process for MUFA- and PUFA-based monoacylglycerols from edible oils.

PubMed

González-Fernández, M J; Ramos-Bueno, R P; Rodríguez-García, I; Guil-Guerrero, J L

2017-08-01

Important health benefits have been attributed to monoacylglycerols (MAGs) due to their various physiological functions, owing to which they become candidates for use as functional foods in order to prevent the onset of certain diseases such as colon cancer. In this work, six edible oils, namely: olive, linseed, sunflower, evening primrose, DHASCO ® and ARASCO ® have been processed to obtain different MUFA- and PUFA- based MAGs. First, the oils were hydrolyzed by means of an enzymatic process using porcine pancreatic lipase and then the reaction products were fractionated by using a liquid chromatography column containing silica gel as stationary phase in order to purify the MAGs-enriched fraction. A second chromatography process was performed using silver nitrate coated silica gel as stationary phase, in order to obtain the different MUFA- and PUFA-based MAGs from the corresponding oils. Overall, MAGs based on oleic, linoleic, α-linolenic, γ-linolenic, arachidonic and docosahexaenoic acids have been isolated in high yields and purities (92.6, 97.4, 95.3, 90.9, 100 and 95.3% purity, respectively). Positional distribution was determined by means of 1 H NMR, which revealed a mix of 1(3) and 2-MAGs in variable proportions in the different MAGs. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.
Delayed Docosahexaenoic Acid Treatment Combined with Dietary Supplementation of Omega-3 Fatty Acids Promotes Long-Term Neurovascular Restoration After Ischemic Stroke.

PubMed

Pu, Hongjian; Jiang, Xiaoyan; Hu, Xiaoming; Xia, Jinchao; Hong, Dandan; Zhang, Wenting; Gao, Yanqin; Chen, Jun; Shi, Yejie

2016-12-01

Prophylactic dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs) has been shown to remarkably ameliorate ischemic brain injury. However, the therapeutic efficacy of n-3 PUFA administration post-stroke, especially its impact on neurovascular remodeling and long-term neurological recovery, has not been fully characterized thus far. In this study, we investigated the effect of n-3 PUFA supplementation, as well as in combination with docosahexaenoic acid (DHA) injections, on long-term stroke outcomes. Mice were subjected to transient middle cerebral artery occlusion (MCAO) before randomly assigned to four groups to receive the following: (1) low dose of n-3 PUFAs as the vehicle control, (2) intraperitoneal DHA injections, (3) n-3 PUFA dietary supplement, or (4) combined treatment of (2) and (3). Neurological deficits and brain atrophy, neurogenesis, angiogenesis, and glial scar formation were assessed up to 28 days after MCAO. Results revealed that groups 2 and 3 showed only marginal reduction in post-stroke tissue loss and attenuation of cognitive deficits. Interestingly, group 4 exhibited significantly reduced tissue atrophy and improved cognitive functions compared to groups 2 and 3 with just a single treatment. Mechanistically, the combined treatment promoted post-stroke neurogenesis and angiogenesis, as well as reduced glial scar formation, all of which significantly correlated with the improved spatial memory in the Morris water maze. These results demonstrate an effective therapeutic regimen to enhance neurovascular restoration and long-term cognitive recovery in the mouse model of MCAO. Combined post-stroke DHA treatment and n-3 PUFA dietary supplementation thus may be a potential clinically translatable therapy for stroke or related brain disorders.
Folded and unfolded conformations of the omega-3 polyunsaturated fatty acid family: ch(3)ch(2)[ch=chch(2)](b)[ch(2)](m)cooh: first principles study.

PubMed

Law, Jacqueline M S; Szori, Milan; Izsak, Robert; Penke, Botond; Csizmadia, Imre G; Viskolcz, Bela

2006-05-11

Polyunsaturated fatty acids (PUFA) like stearidonic acid (SDA;18:4 n-3) eicosapentaenoic acid (EPA; 20:5 n-3), and docosahexaenoic acid (DHA; 22:6 n-3) and its chain fragment models were studied at B3LYP/6-31G(d) levels of theory. Significant conformations for the cis and trans isomers were selected to obtained the thermodynamic functions (DeltaH, DeltaS, DeltaG) for the cis-trans isomerization and for folding using the B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d) level of theory. The structural analysis shows that there are significant differences in thermodynamic function of the trans- and cis-PUFAs. The trans-cis isomerization energy values reinforce the consistency and the relative accuracy of theoretical model calculations. The observed flexibility of naturally cis PUFAs could be explained by a very special "smooth basin" PES of the motif of sp(2)-sp(3)-sp(2) hybrid states as reported previously (J. Phys. Chem. A 2005, 109, 520-533). We assumed that intrinsic thermodynamic functions may describe this flexible folding process. The folding enthalpy as well as the folding entropy suggests that there is a new role of the cis-PUFAs in membranes: these cis isomers may have a strong influence on membrane stability and permeability. The average length of the cis helix and beta PUFA was approximated. The difference between the lengths of these two structures is approximately 10 A.
Omega-3 fatty acids modulate Weibel-Palade body degranulation and actin cytoskeleton rearrangement in PMA-stimulated human umbilical vein endothelial cells.

PubMed

Bürgin-Maunder, Corinna S; Brooks, Peter R; Russell, Fraser D

2013-11-08

Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) produce cardiovascular benefits by improving endothelial function. Endothelial cells store von Willebrand factor (vWF) in cytoplasmic Weibel-Palade bodies (WPBs). We examined whether LC n-3 PUFAs regulate WPB degranulation using cultured human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with or without 75 or 120 µM docosahexaenoic acid or eicosapentaenoic acid for 5 days at 37 °C. WPB degranulation was stimulated using phorbol 12-myristate 13-acetate (PMA), and this was assessed by immunocytochemical staining for vWF. Actin reorganization was determined using phalloidin-TRITC staining. We found that PMA stimulated WPB degranulation, and that this was significantly reduced by prior incubation of cells with LC n-3 PUFAs. In these cells, WPBs had rounded rather than rod-shaped morphology and localized to the perinuclear region, suggesting interference with cytoskeletal remodeling that is necessary for complete WPB degranulation. In line with this, actin rearrangement was altered in cells containing perinuclear WPBs, where cells exhibited a thickened actin rim in the absence of prominent cytoplasmic stress fibers. These findings indicate that LC n-3 PUFAs provide some protection against WBP degranulation, and may contribute to an improved understanding of the anti-thrombotic effects previously attributed to LC n-3 PUFAs.
The Fatty Acid Profile and Oxidative Stability of Meat from Turkeys Fed Diets Enriched with n-3 Polyunsaturated Fatty Acids and Dried Fruit Pomaces as a Source of Polyphenols.

PubMed

Juskiewicz, Jerzy; Jankowski, Jan; Zielinski, Henryk; Zdunczyk, Zenon; Mikulski, Dariusz; Antoszkiewicz, Zofia; Kosmala, Monika; Zdunczyk, Przemyslaw

2017-01-01

The aim of this study was to determine the efficacy of different dietary fruit pomaces in reducing lipid oxidation in the meat of turkeys fed diets with a high content of n-3 polyunsaturated fatty acids (PUFAs). Over a period of 4 weeks before slaughter, turkeys were fed diets with the addition of 5% dried apple, blackcurrant, strawberry and seedless strawberry pomaces (groups AP, BP, SP and SSP, respectively) and 2.5% linseed oil. Pomaces differed in the content (from 5.5 in AP to 43.1 mg/g in SSP) and composition of polyphenols Proanthocyanidins were the main polyphenolic fraction in all pomaces, AP contained flavone glycosides and dihydrochalcones, BP contained anthocyanins, and SP and SSP-ellagitannins. The n-6/n-3 PUFA ratio in all diets was comparable and lower than 2:1. In comparison with groups C and AP, the percentage of n-3 PUFAs in the total fatty acid pool of white meat from the breast muscles of turkeys in groups BP, SP and SSP was significantly higher, proportionally to the higher content of α-linolenic acid in berry pomaces. The fatty acid profile of dark meat from thigh muscles, including the n-6/n-3 PUFA ratio, was similar and lower than 3:1 in all groups. Vitamin A levels in raw breast muscles were higher in group AP than in groups C and BP (P<0.05). The addition of fruit pomaces to turkey diets lowered vitamin E concentrations (P = 0.001) in raw breast muscles relative to group C. Diets supplemented with fruit pomaces significantly lowered the concentration of thiobarbituric acid reactive substances (TBARS) in raw, frozen and cooked meat. Our results indicate that the dietary application of dried fruit pomaces increases the oxidative stability of meat from turkeys fed linseed oil, and strawberry pomace exerted the most desirable effects due to its highest polyphenol content and antioxidant potential.
The Fatty Acid Profile and Oxidative Stability of Meat from Turkeys Fed Diets Enriched with n-3 Polyunsaturated Fatty Acids and Dried Fruit Pomaces as a Source of Polyphenols

PubMed Central

Juskiewicz, Jerzy; Jankowski, Jan; Zielinski, Henryk; Zdunczyk, Zenon; Mikulski, Dariusz; Antoszkiewicz, Zofia; Kosmala, Monika; Zdunczyk, Przemyslaw

2017-01-01

The aim of this study was to determine the efficacy of different dietary fruit pomaces in reducing lipid oxidation in the meat of turkeys fed diets with a high content of n-3 polyunsaturated fatty acids (PUFAs). Over a period of 4 weeks before slaughter, turkeys were fed diets with the addition of 5% dried apple, blackcurrant, strawberry and seedless strawberry pomaces (groups AP, BP, SP and SSP, respectively) and 2.5% linseed oil. Pomaces differed in the content (from 5.5 in AP to 43.1 mg/g in SSP) and composition of polyphenols Proanthocyanidins were the main polyphenolic fraction in all pomaces, AP contained flavone glycosides and dihydrochalcones, BP contained anthocyanins, and SP and SSP—ellagitannins. The n-6/n-3 PUFA ratio in all diets was comparable and lower than 2:1. In comparison with groups C and AP, the percentage of n-3 PUFAs in the total fatty acid pool of white meat from the breast muscles of turkeys in groups BP, SP and SSP was significantly higher, proportionally to the higher content of α-linolenic acid in berry pomaces. The fatty acid profile of dark meat from thigh muscles, including the n-6/n-3 PUFA ratio, was similar and lower than 3:1 in all groups. Vitamin A levels in raw breast muscles were higher in group AP than in groups C and BP (P<0.05). The addition of fruit pomaces to turkey diets lowered vitamin E concentrations (P = 0.001) in raw breast muscles relative to group C. Diets supplemented with fruit pomaces significantly lowered the concentration of thiobarbituric acid reactive substances (TBARS) in raw, frozen and cooked meat. Our results indicate that the dietary application of dried fruit pomaces increases the oxidative stability of meat from turkeys fed linseed oil, and strawberry pomace exerted the most desirable effects due to its highest polyphenol content and antioxidant potential. PMID:28076425
Production and concentration of monoacylglycerols rich in omega-3 polyunsaturated fatty acids by enzymatic glycerolysis and molecular distillation.

PubMed

Solaesa, Ángela García; Sanz, María Teresa; Falkeborg, Mia; Beltrán, Sagrario; Guo, Zheng

2016-01-01

Production of monoacylglycerols (MAGs) rich in ω-3 polyunsaturated fatty acids (n-3 PUFAs) was conducted through short path distillation (SPD) of an acylglycerol mixture (containing 67% MAGs) produced by enzymatic glycerolysis of sardine oil with glycerol. A stepwise SPD process in a UIC KDL 5 system (vacuum 10(-3)mbar, feeding flow 1.0 mL/min) was proceeded: the first distillation performed at evaporator temperature (TE) of 110 °C to remove glycerol completely and most of FFAs; and the second distillation at optimized TE 155 °C; resulting in a stream distillate with 91% purity and 94% overall recovery of MAGs. This work also demonstrated that SPD is able to concentrate n-3 PUFAs in MAG form by distilling at proper TE e.g. 125 °C, where n-3 PUFAs are concentrated in the residues. Moreover, this work mapped out a complete processing diagram for scalable production of n-3 PUFAs enriched MAGs as potential food emulsifier and ingredient. Copyright © 2015 Elsevier Ltd. All rights reserved.
N-3 polyunsaturated fatty acids supplementation does not affect changes of lipid metabolism induced in rats by altered thyroid status.

PubMed

Rauchová, H; Vokurková, M; Pavelka, S; Behuliak, M; Tribulová, N; Soukup, T

2013-07-01

Epidemiological studies have demonstrated that n-3 polyunsaturated fatty acid (PUFA) consumption is associated with a reduced risk of atherosclerosis and hyperlipidemia. It is well known that lipid metabolism is also influenced by thyroid hormones. The aim of our study was to test whether n-3 PUFA supplementation (200 mg/kg of body weight/day for 6 weeks given intragastrically) would affect lipid metabolism in Lewis male rats with altered thyroid status. Euthyroid, hypothyroid, and hyperthyroid status of experimental groups was well defined by plasma levels of triiodothyronine, the activity of liver mitochondrial glycerol-3-phosphate dehydrogenase, and by relative heart weight. Fasting blood glucose levels were significantly higher in the hyperthyroid compared to the euthyroid and hypothyroid rats (5.0±0.2 vs. 3.7±0.4 and 4.4±0.2 mmol/l, respectively). In hyperthyroid animals, the concentration of plasma postprandial triglycerides was also increased compared to euthyroid and hypothyroid rats (0.9±0.1 vs. 0.5±0.1 and 0.4±0.1 mmol/l, respectively). On the other hand, hypothyroidism compared to euthyroid and hyperthyroid status was associated with elevated plasma levels of total cholesterol (2.6±0.2 vs. 1.5±0.1 and 1.6±0.1 mmol/l, respectively), LDL cholesterol (0.9±0.1 vs. 0.4±0.1 and 0.2±0.1 mmol/l, respectively) as well as HDL cholesterol (1.6±0.1 vs. 1.0±0.1 and 1.3±0.1 mmol/l, respectively). Supplementation of n-3 PUFA in the present study did not significantly modify either relative heart weight or glucose and lipid levels in any thyroid status. © Georg Thieme Verlag KG Stuttgart · New York.
Liquid lipases for enzymatic concentration of n-3 polyunsaturated fatty acids in monoacylglycerols via ethanolysis: Catalytic specificity and parameterization.

PubMed

He, Yongjin; Li, Jingbo; Kodali, Sitharam; Balle, Thomas; Chen, Bilian; Guo, Zheng

2017-01-01

This work examined catalytic specificity and fatty acid selectivity of five liquid lipases C. antarctica lipase A and B (CAL-A/B), and lipase TL (T. lanuginosus), Eversa Transfrom and NS in ethanolysis of fish oil with the aim to concentrate n-3 PUFAs into monoacylglycerols (MAGs) products. Lipase TL, Eversa Transform & NS entail a much faster reaction and produce higher MAGs yield (>30%); whereas CAL-A obtains the highest concentration of n-3 PUFAs/DHA/EPA into MAGs products (88.30%); followed by lipase NS (81.02%). 13 C NMR analysis indicates that CAL-B and lipase TL are sn-1,3 specific; but CAL-A and lipase Eversa Transform are non-regiospecific or weak sn-2 specific; which plausibly explains high enrichment effect of the latter two lipases. All liquid lipases are observed reusable for a certain times (lipase Eversa Transform up to 12 times), demonstrating their competitive advantage over immobilized form for industrial application because of their higher activity and cheaper operation cost. Copyright © 2016 Elsevier Ltd. All rights reserved.
Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids

PubMed Central

2011-01-01

Background The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]). Results Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic low density lipoprotein (LDL) receptor, sterol regulatory element binding protein (SREBP)-1c and acyl-CoA: cholesterol acyl transferase-2 (ACAT) mRNA and protein (p < 0.05), and higher hepatic apolipoprotein (apo) B-100 and apo E protein levels. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower non-HDL cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic SREBP-1c (p < 0.05) but not apo B-100, apo E or ACAT-2 mRNA or protein levels. Independent of cholesterol status, fish oil fed hamsters had lower HDL cholesterol concentrations (p < 0.001), which were associated with lower hepatic apoA-I protein levels (p < 0.05). Conclusion These data suggest disturbing cholesterol homeostasis in F1B hamsters alters their response to dietary fatty acids, which is reflected in altered plasma lipoprotein patterns and regulation of genes associated with their metabolism. PMID:22018327
Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids.

PubMed

Lecker, Jaime L; Matthan, Nirupa R; Billheimer, Jeffrey T; Rader, Daniel J; Lichtenstein, Alice H

2011-10-21

The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]). Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic low density lipoprotein (LDL) receptor, sterol regulatory element binding protein (SREBP)-1c and acyl-CoA: cholesterol acyl transferase-2 (ACAT) mRNA and protein (p < 0.05), and higher hepatic apolipoprotein (apo) B-100 and apo E protein levels. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower non-HDL cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic SREBP-1c (p < 0.05) but not apo B-100, apo E or ACAT-2 mRNA or protein levels. Independent of cholesterol status, fish oil fed hamsters had lower HDL cholesterol concentrations (p < 0.001), which were associated with lower hepatic apoA-I protein levels (p < 0.05). These data suggest disturbing cholesterol homeostasis in F1B hamsters alters their response to dietary fatty acids, which is reflected in altered plasma lipoprotein patterns and regulation of genes associated with their metabolism.
Understanding diet and modeling changes in the omega-3 and omega-6 fatty acid composition of U.S. garrison foods for active duty personnel.

PubMed

Marriott, Bernadette P; Yu, Karina; Majchrzak-Hong, Sharon; Johnson, Jeremiah; Hibbeln, Joseph R

2014-11-01

Research indicates that dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are important in reducing the risk of mental illness. We used the DoD Survey of Health Related Behaviors among Active Duty Military Personnel (HRBS) to assess current military dietary patterns and meal locations. We used the Lands Equation to model PUFAs in a sample Garrison diet and the nutritional impact of substitution of foods higher in omega-3 PUFAs and lower in omega-6 PUFAs on tissue composition. The military diet was very poor quality compared to 2010 Healthy People Guidelines. A representative Garrison diet does not meet our estimated healthy n-3 HUFA intake at 3.5 g/d, corresponding with a tissue composition of 60% n-3 in HUFA (i.e., 40% n-6 in HUFA). Substitution of n-3 rich eggs, poultry, pork and other food commodities, combined with use on low linoleic acid oils, may contribute significantly to attaining healthier n-6/n-3 proportions in the tissue. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.
Association between dietary intake of n-3 polyunsaturated fatty acids and severity of skin photoaging in a middle-aged Caucasian population.

PubMed

Latreille, Julie; Kesse-Guyot, Emmanuelle; Malvy, Denis; Andreeva, Valentina; Galan, Pilar; Tschachler, Erwin; Hercberg, Serge; Guinot, Christiane; Ezzedine, Khaled

2013-12-01

Intake of long-chain n-3 polyunsaturated fatty acid (PUFAs) supplementation has been reported to be associated with reduced UVB-erythemal sensitivity, but their relationship to photoaging has not been studied to date. To investigate associations between daily n-3 PUFA intake and the severity of skin photoaging. A cross-sectional study was conducted on 2919 subjects aged 45-60 years from the SU.VI.MAX cohort. At baseline, trained investigators graded the severity of facial skin photoaging using a validated 6-grade scale during a clinical examination. Intake of α-linolenic (ALA), eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic acids (DHA) were evaluated by dietary source using ten 24-h dietary record questionnaires during the first 2.5 years of the follow-up period. After adjustment for possible confounders, severe photoaging was found to be inversely associated with higher intake of ALA in men and with higher intake of EPA in women. When considering the different food sources of ALA for men, an inverse association appeared between severe photoaging and ALA from vegetable oils, as well as with ALA from fruit and vegetables, whereas no association was observed for ALA from dairy products. In women, ALA from vegetable oils also tended to be inversely linked to photoaging. These findings suggest a possible benefit effect of n-3 PUFAs on skin aging. Nonetheless, further epidemiological studies are necessary to confirm our results and to gain additional insights into underlying mechanisms. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
TLR3 deficiency in herpes simplex encephalitis: high allelic heterogeneity and recurrence risk.

PubMed

Lim, Hye Kyung; Seppänen, Mikko; Hautala, Timo; Ciancanelli, Michael J; Itan, Yuval; Lafaille, Fabien G; Dell, William; Lorenzo, Lazaro; Byun, Minji; Pauwels, Elodie; Rönnelid, Ylva; Cai, Xin; Boucherit, Soraya; Jouanguy, Emmanuelle; Paetau, Anders; Lebon, Pierre; Rozenberg, Flore; Tardieu, Marc; Abel, Laurent; Yildiran, Alisan; Vergison, Anne; Roivainen, Reina; Etzioni, Amos; Tienari, Pentti J; Casanova, Jean-Laurent; Zhang, Shen-Ying

2014-11-18

To determine the proportion of children with herpes simplex encephalitis (HSE) displaying TLR3 deficiency, the extent of TLR3 allelic heterogeneity, and the specific clinical features of TLR3 deficiency. We determined the sequence of all exons of TLR3 in 110 of the 120 patients with HSE enrolled in our study who do not carry any of the previously described HSE-predisposing mutations of TLR3 pathway genes (TLR3, UNC93B1, TRIF, TRAF3, and TBK1). All the new mutant TLR3 alleles detected were characterized experimentally in-depth to establish the causal relationship between the genotype and phenotype. In addition to the 3 previously reported TLR3-deficient patients from the same cohort, 6 other children or young adults with HSE carry 1 of 5 unique or extremely rare (minor allele frequency <0.001) missense TLR3 alleles. Two alleles (M374T, D592N) heterozygous in 3 patients are not deleterious in vitro. The other 3 are deleterious via different mechanisms: G743D+R811I and L360P heterozygous in 2 patients are loss-of-function due to low levels of expression and lack of cleavage, respectively, and R867Q homozygous in 1 patient is hypomorphic. The 3 patients' fibroblasts display impaired TLR3 responses and enhanced herpes simplex virus 1 susceptibility. Overall, TLR3 deficiency is therefore found in 6 (5%) of the 120 patients studied. There is high allelic heterogeneity, with 3 forms of autosomal dominant partial defect by negative dominance or haploinsufficiency, and 2 forms of autosomal recessive defect with complete or partial deficiency. Finally, 4 (66%) of the 6 TLR3-deficient patients had at least 1 late relapse of HSE, whereas relapse occurred in only 12 (10%) of the total cohort of 120 patients. Childhood-onset HSE is due to TLR3 deficiency in a traceable fraction of patients, in particular the ones with HSE recurrence. Mutations in TLR3 and TLR3 pathway genes should be searched and experimentally studied in children with HSE, and patients with proven TLR3
Genetic Variants of the FADS Gene Cluster and ELOVL Gene Family, Colostrums LC-PUFA Levels, Breastfeeding, and Child Cognition

PubMed Central

Morales, Eva; Bustamante, Mariona; Gonzalez, Juan Ramon; Guxens, Monica; Torrent, Maties; Mendez, Michelle; Garcia-Esteban, Raquel; Julvez, Jordi; Forns, Joan; Vrijheid, Martine; Molto-Puigmarti, Carolina; Lopez-Sabater, Carmen; Estivill, Xavier; Sunyer, Jordi

2011-01-01

Introduction Breastfeeding effects on cognition are attributed to long-chain polyunsaturated fatty acids (LC-PUFAs), but controversy persists. Genetic variation in fatty acid desaturase (FADS) and elongase (ELOVL) enzymes has been overlooked when studying the effects of LC-PUFAs supply on cognition. We aimed to: 1) to determine whether maternal genetic variants in the FADS cluster and ELOVL genes contribute to differences in LC-PUFA levels in colostrum; 2) to analyze whether these maternal variants are related to child cognition; and 3) to assess whether children's variants modify breastfeeding effects on cognition. Methods Data come from two population-based birth cohorts (n = 400 mother-child pairs from INMA-Sabadell; and n = 340 children from INMA-Menorca). LC-PUFAs were measured in 270 colostrum samples from INMA-Sabadell. Tag SNPs were genotyped both in mothers and children (13 in the FADS cluster, 6 in ELOVL2, and 7 in ELOVL5). Child cognition was assessed at 14 mo and 4 y using the Bayley Scales of Infant Development and the McCarthy Scales of Children's Abilities, respectively. Results Children of mothers carrying genetic variants associated with lower FADS1 activity (regulating AA and EPA synthesis), higher FADS2 activity (regulating DHA synthesis), and with higher EPA/AA and DHA/AA ratios in colostrum showed a significant advantage in cognition at 14 mo (3.5 to 5.3 points). Not being breastfed conferred an 8- to 9-point disadvantage in cognition among children GG homozygote for rs174468 (low FADS1 activity) but not among those with the A allele. Moreover, not being breastfed resulted in a disadvantage in cognition (5 to 8 points) among children CC homozygote for rs2397142 (low ELOVL5 activity), but not among those carrying the G allele. Conclusion Genetically determined maternal supplies of LC-PUFAs during pregnancy and lactation appear to be crucial for child cognition. Breastfeeding effects on cognition are modified by child genetic variation in
High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

PubMed

Gwon, Do Hyeong; Hwang, Tae Woong; Ro, Ju-Ye; Kang, Yoon-Joong; Jeong, Jin Young; Kim, Do-Kyung; Lim, Kyu; Kim, Dong Woon; Choi, Dae Eun; Kim, Jwa-Jin

2017-09-30

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham ( n = 10), fat-1 sham ( n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI ( n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.
PUFA levels in erythrocyte membrane phospholipids are differentially associated with colorectal adenoma risk.

PubMed

Rifkin, Samara B; Shrubsole, Martha J; Cai, Qiuyin; Smalley, Walter E; Ness, Reid M; Swift, Larry L; Zheng, Wei; Murff, Harvey J

2017-06-01

Dietary intake of PUFA has been associated with colorectal neoplasm risk; however, results from observational studies have been inconsistent. Most prior studies have utilised self-reported dietary measures to assess fatty acid exposure which might be more susceptible to measurement error and biases compared with biomarkers. The purpose of this study was to determine whether erythrocyte phospholipid membrane PUFA percentages are associated with colorectal adenoma risk. We included data from 904 adenoma cases and 835 polyp-free controls who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case-control study. Erythrocyte membrane PUFA percentages were measured using GC. Conditional logistic regression was used to calculate adjusted OR for risk of colorectal adenomas with erythrocyte membrane PUFA. Higher erythrocyte membrane percentages of arachidonic acid was associated with an increased risk of colorectal adenomas (adjusted OR 1·66; 95 % CI 1·05, 2·62, P trend=0·02) comparing the highest tertile to the lowest tertile. The effect size for arachidonic acid was more pronounced when restricting the analysis to advanced adenomas only. Higher erythrocyte membrane EPA percentages were associated with a trend towards a reduced risk of advanced colorectal adenomas (P trend=0·05). Erythrocyte membrane arachidonic acid percentages are associated with an increased risk of colorectal adenomas.
Maternal intake of seafood and supplementary long chain n-3 poly-unsaturated fatty acids and preterm delivery.

PubMed

Brantsæter, Anne Lise; Englund-Ögge, Linda; Haugen, Margareta; Birgisdottir, Bryndis Eva; Knutsen, Helle Katrine; Sengpiel, Verena; Myhre, Ronny; Alexander, Jan; Nilsen, Roy M; Jacobsson, Bo; Meltzer, Helle Margrete

2017-01-19

Preterm delivery increases the risk of neonatal morbidity and mortality. Studies suggest that maternal diet may affect the prevalence of preterm delivery. The aim of this study was to assess whether maternal intakes of seafood and marine long chain n-3 polyunsaturated fatty acids (LCn-3PUFA) from supplements were associated with preterm delivery. The study population included 67,007 women from the Norwegian Mother and Child Cohort Study. Maternal food and supplement intakes were assessed by a validated self-reported food frequency questionnaire in mid-pregnancy. Information about gestational duration was obtained from the Medical Birth Registry of Norway. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between total seafood, lean fish, fatty fish, and LCn-3PUFA intakes and preterm delivery. Preterm was defined as any onset of delivery before gestational week 37, and as spontaneous or iatrogenic deliveries and as preterm delivery at early, moderate, and late preterm gestations. Lean fish constituted 56%, fatty fish 34% and shellfish 10% of seafood intake. Any intake of seafood above no/rare intake (>5 g/d) was associated with lower prevalence of preterm delivery. Adjusted HRs were 0.76 (CI: 0.66, 0.88) for 1-2 servings/week (20-40 g/d), 0.72 (CI: 0.62, 0.83) for 2-3 servings/week (40-60 g/d), and 0.72 (CI: 0.61, 0.85) for ≥3 servings/week (>60 g/d), p-trend <0.001. The association was seen for lean fish (p-trend: 0.005) but not for fatty fish (p-trend: 0.411). The intake of supplementary LCn-3PUFA was associated only with lower prevalence of early preterm delivery (before 32 gestational weeks), while increasing intake of LCn-3PUFA from food was associated with lower prevalence of overall preterm delivery (p-trend: 0.002). Any seafood intake above no/rare was associated with lower prevalence of both spontaneous and iatrogenic preterm delivery, and with lower prevalence of late preterm delivery. Any
Ability of the gut microbiota to produce PUFA-derived bacterial metabolites: Proof of concept in germ-free versus conventionalized mice.

PubMed

Druart, Céline; Bindels, Laure B; Schmaltz, Robert; Neyrinck, Audrey M; Cani, Patrice D; Walter, Jens; Ramer-Tait, Amanda E; Delzenne, Nathalie M

2015-08-01

The gut microbiota is able to modulate host physiology through the production of bioactive metabolites. Our recent studies suggest that changes in gut microbiota composition upon prebiotics supplementation alter tissue levels of PUFA-derived metabolites in mice. However, in vivo evidence that gut microbes produces PUFA-derived metabolites is lacking. This study aimed to decipher the contribution of gut microbes versus that of the host in PUFA-derived metabolite production. To achieve this goal, we compared the proportion of PUFA-derived metabolites and the expression of fatty acid desaturases in germ-free (GF) and conventionalized (CONV) mice fed either a low fat or Western diet. Higher concentrations of PUFA-derived metabolites were found in the colonic contents of conventionalized mice (CONV) mice compared to GF mice. The abundance of these metabolites in host tissues was modulated by dietary treatments but not by microbial status. Although microbial status did significantly influence desaturase expression, no correlations between host enzymes and tissue PUFA-derived metabolite levels were observed. Together, these results highlight the ability of the gut microbiota to produce PUFA-derived metabolites from dietary PUFA. However, microbial production of these metabolites in colonic contents is not necessarily associated with modifications of their concentration in host tissues. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Oiling the brain: a review of randomized controlled trials of omega-3 fatty acids in psychopathology across the lifespan.

PubMed

Sinn, Natalie; Milte, Catherine; Howe, Peter R C

2010-02-01

Around one in four people suffer from mental illness at some stage in their lifetime. There is increasing awareness of the importance of nutrition, particularly omega-3 polyunsaturated fatty acids (n-3 PUFA), for optimal brain development and function. Hence in recent decades, researchers have explored effects of n-3 PUFA on mental health problems over the lifespan, from developmental disorders in childhood, to depression, aggression, and schizophrenia in adulthood, and cognitive decline, dementia and Alzheimer's disease in late adulthood. This review provides an updated overview of the published and the registered clinical trials that investigate effects of n-3 PUFA supplementation on mental health and behavior, highlighting methodological differences and issues.

MSH3 protein expression and nodal status in MLH1-deficient colorectal cancers.

PubMed

Laghi, Luigi; Bianchi, Paolo; Delconte, Gabriele; Celesti, Giuseppe; Di Caro, Giuseppe; Pedroni, Monica; Chiaravalli, Anna Maria; Jung, Barbara; Capella, Carlo; de Leon, Maurizio Ponz; Malesci, Alberto

2012-06-01

Patients with colorectal cancers (CRC) and high microsatellite instability (MSI) have a better outcome than their chromosome-unstable counterpart. Given the heterogeneity of microsatellite-unstable CRCs, we wanted to see whether any MSI-associated molecular features are specifically associated with prognosis. One hundred and nine MSI-high CRCs were typed for primary mismatch repair (MMR) defect and for secondary loss of MMR proteins. Frameshifts at seven target genes, mutations in the RAS pathway, and methylation at MLH1/CDKN2A promoters were also searched. The interplay of molecular findings with clinicopathologic features and patient survival was analyzed. Of 84 MLH1-deficient CRCs, 31 (36.9%) had MSH3 and 11 (13.1%) had MSH6 loss (P < 0.001), biallelic frameshift mutations at mononucleotide repeats accounting for most (78%) MSH3 losses. As compared with MSH3-retaining cancers, MLH1-deficient tumors with MSH3 loss showed a higher number of mutated target genes (3.94 ± 1.56 vs. 2.79 ± 1.75; P = 0.001), absence of nodal involvement at pathology [N0; OR, 0.11; 95% confidence interval (CI), 0.04-0.43, P < 0.001], and better disease-free survival (P = 0.06). No prognostic value was observed for KRAS status and for MLH1/CDKN2A promoter methylation. The association between MSH3 loss and N0 was confirmed in an independent cohort of 71 MLH1-deficient CRCs (OR, 0.23; 95% CI, 0.06-0.83, P = 0.02). MLH1-deficient CRCs not expressing MSH3 have a more severe MSI, a lower rate of nodal involvement, and a better postsurgical outcome.
The effect of omega-3 polyunsaturated fatty acid supplementation on emotional dysregulation, oppositional behaviour and conduct problems in ADHD: A systematic review and meta-analysis.

PubMed

Cooper, Ruth E; Tye, Charlotte; Kuntsi, Jonna; Vassos, Evangelos; Asherson, Philip

2016-01-15

A number of randomised controlled trials report a beneficial effect of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on emotional lability (EL) and related domains (e.g. oppositional behaviour, conduct problems). Given that n-3 PUFA supplementation shows a significant effect on reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) and that EL and related behaviours commonly co-occurs with ADHD, it is important that there is a more conclusive picture as to the effect of n-3 PUFA on these co-occurring clinical domains. Databases (Ovid Medline, Embase, Psychinfo) were searched for trials assessing the effects of n-3 PUFA on EL, oppositional behaviour, aggression and conduct problems. We included trials in children who had ADHD or a related neurodevelopmental disorder. Of the 1775 identified studies, 10 were included in the meta-analysis. In the primary analyses n-3 PUFA supplementation did not show improvements in measures of EL, oppositional behaviour, conduct problems or aggression. However subgroup analyses of higher quality studies and those meeting strict inclusion criteria found a significant reduction in EL and oppositional behaviour. A number of treatment effects may have failed to reach statistical significance due to small sample sizes and within and between study heterogeneity in terms of design and study participants. These results exclude the possibility of moderate to large effects. They provide suggestive evidence of small effects of n-3 PUFA on reducing EL and oppositional behaviour in subgroups of children with ADHD. Copyright © 2015 Elsevier B.V. All rights reserved.
Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance - A review.

PubMed

Saini, Ramesh Kumar; Keum, Young-Soo

2018-06-15

Linoleic acid (LA) (n-6) and α-linolenic acid (ALA) (n-3) are essential fatty acids (EFAs) as they cannot be synthesized by humans or other higher animals. In the human body, these fatty acids (FAs) give rise to arachidonic acid (ARA, n-6), eicosapentaenoic acid (EPA, n-3), and docosahexaenoic acid (DHA, n-3) that play key roles in regulating body homeostasis. Locally acting bioactive signaling lipids called eicosanoids derived from these FAs also regulate diverse homeostatic processes. In general, ARA gives rise to pro-inflammatory eicosanoids whereas EPA and DHA give rise to anti-inflammatory eicosanoids. Thus, a proportionally higher consumption of n-3 PUFAs can protect us against inflammatory diseases, cancer, cardiovascular diseases, and other chronic diseases. The present review summarizes major sources, intake, and global consumption of n-3 and n-6 PUFAs. Their metabolism to biosynthesize long-chain PUFAs and eicosanoids and their roles in brain metabolism, cardiovascular disease, obesity, cancer, and bone health are also discussed. Copyright © 2018 Elsevier Inc. All rights reserved.
Effect of varying dietary levels of LC-PUFA and vegetable oil sources on performance and fatty acids of Senegalese sole post larvae: puzzling results suggest complete biosynthesis pathway from C18 PUFA to DHA.

PubMed

Navarro-Guillén, Carmen; Engrola, Sofia; Castanheira, Filipa; Bandarra, Narcisa; Hachero-Cruzado, Ismael; Tocher, Douglas R; Conceição, Luís E C; Morais, Sofia

2014-01-01

Lipid nutrition of marine fish larvae has focused on supplying essential fatty acids (EFA) at high levels to meet requirements for survival, growth and development. However, some deleterious effects have been reported suggesting that excessive supply of EFA might result in insufficient supply of energy substrates, particularly in species with lower EFA requirements such as Senegalese sole (Solea senegalensis). This study addressed how the balance between EFA and non-EFA (better energy sources) affects larval performance, body composition and metabolism and retention of DHA, by formulating enrichment emulsions containing two different vegetable oil sources (olive oil or soybean oil) and three DHA levels. DHA positively affected growth and survival, independent of oil source, confirming that for sole post-larvae it is advantageous to base enrichments on vegetable oils supplying higher levels of energy, and supplement these with a DHA-rich oil. In addition, body DHA levels were generally comparable considering the large differences in their dietary supply, suggesting that the previously reported ∆4 fatty acyl desaturase (fad) operates in vivo and that DHA was synthesized at physiologically significant rates through a mechanism involving transcriptional up-regulation of ∆4fad, which was significantly up-regulated in the low DHA treatments. Furthermore, data suggested that DHA biosynthesis may be regulated by an interaction between dietary n-3 and n-6 PUFA, as well as by levels of LC-PUFA, and this may, under certain nutritional conditions, lead to DHA production from C18 precursors. The molecular basis of putative fatty acyl ∆5 and ∆6 desaturation activities remains to be fully determined as thorough searches have found only a single (∆4) Fads2-type transcript. Therefore, further studies are required but this might represent a unique activity described within vertebrate fads. © 2013.
High levels of retinal membrane docosahexaenoic acid increase susceptibility to stress-induced degenerations⃞

PubMed Central

Tanito, Masaki; Brush, Richard S.; Elliott, Michael H.; Wicker, Lea D.; Henry, Kimberly R.; Anderson, Robert E.

2009-01-01

The fat-1 gene cloned from C. elegans encodes an n-3 fatty acid desaturase that converts n-6 to n-3 PUFA. Mice carrying the fat-1 transgene and wild-type controls were fed an n-3-deficient/n-6-enriched diet [fat-1- safflower oil (SFO) and wt-SFO, respectively]. Fatty acid profiles of rod outer segments (ROS), cerebellum, plasma, and liver demonstrated significantly lower n-6/n-3 ratios and higher docosahexaenoic acid (DHA) levels in fat-1-SFO compared with wt-SFO. When mice were exposed to light stress: 1) the outer nuclear layer (ONL) thickness was reduced; 2) amplitudes of the electroretinogram (ERG) were lower; 3) the number of apoptotic photoreceptor cells was greater; and 4) modification of retinal proteins by 4-hydroxyhexenal (4-HHE), an end-product of n-3 PUFA oxidation was increased in both fat-1-SFO and wt mice fed a regular lab chow diet compared with wt-SFO. The results indicate a positive correlation between the level of DHA, the degree of n-3 PUFA lipid peroxidation, and the vulnerability of the retina to photooxidative stress. In mice not exposed to intense light, the reduction in DHA resulted in reduced efficacy in phototransduction gain steps, while no differences in the retinal morphology or retinal biochemistry. These results highlight the dual roles of DHA in cellular physiology and pathology. PMID:19023138
Potential for daily supplementation of n-3 fatty acids to reverse symptoms of dry eye in mice.

PubMed

Harauma, Akiko; Saito, Junpei; Watanabe, Yoshitake; Moriguchi, Toru

2014-06-01

The purpose of this study was to determine the change in tear volume, as a predominant symptom of dry eye syndrome, in dietary n-3 fatty acid deficient mice compared with n-3 fatty acid adequate mice. The tear volume in n-3 fatty acid deficient mice was significantly lower than that in n-3 fatty acid adequate mice. In addition, the concentration of n-3 fatty acid in the lacrimal and meibomian glands, which affects the production of tears, was markedly decreased compared with n-3 fatty acid adequate mice. However, the tear volume recovered almost completely after one week of continuous administration of fish oil containing EPA and DHA in n-3 fatty acid deficient mice. Also, the concentration of DHA in the meibomian gland of n-3 fatty acid deficient group recovered to approximately 80% more than that of n-3 fatty acid adequate group. These results suggested that dietary n-3 fatty acids deficiency showed reversible dry eye syndrome, and that n-3 fatty acids have an important role in the production of tears. Copyright © 2014 Elsevier Ltd. All rights reserved.
Omega-3 polyunsaturated fatty acids and chronic stress-induced modulations of glutamatergic neurotransmission in the hippocampus.

PubMed

Hennebelle, Marie; Champeil-Potokar, Gaëlle; Lavialle, Monique; Vancassel, Sylvie; Denis, Isabelle

2014-02-01

Chronic stress causes the release of glucocorticoids, which greatly influence cerebral function, especially glutamatergic transmission. These stress-induced changes in neurotransmission could be counteracted by increasing the dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Numerous studies have described the capacity of n-3 PUFAs to help protect glutamatergic neurotransmission from damage induced by stress and glucocorticoids, possibly preventing the development of stress-related disorders such as depression or anxiety. The hippocampus contains glucocorticoid receptors and is involved in learning and memory. This makes it particularly sensitive to stress, which alters certain aspects of hippocampal function. In this review, the various ways in which n-3 PUFAs may prevent the harmful effects of chronic stress, particularly the alteration of glutamatergic synapses in the hippocampus, are summarized. © 2014 International Life Sciences Institute.
Pbx3 Deficiency Results in Central Hypoventilation

PubMed Central

Rhee, Joon Whan; Arata, Akiko; Selleri, Licia; Jacobs, Yakop; Arata, Satoru; Onimaru, Hiroshi; Cleary, Michael L.

2004-01-01

Pbx proteins comprise a family of TALE (three amino acid loop extension) class homeodomain transcription factors that are implicated in developmental gene expression through their abilities to form hetero-oligomeric DNA-binding complexes and function as transcriptional regulators in numerous cell types. We demonstrate here that one member of this family, Pbx3, is expressed at high levels predominantly in the developing central nervous system, including a region of the medulla oblongata that is implicated in the control of respiration. Pbx3-deficient mice develop to term but die within a few hours of birth from central respiratory failure due to abnormal activity of inspiratory neurons in the medulla. This partially phenocopies the defect in mice deficient for Rnx, a metaHox homeodomain transcription factor, that we demonstrate here is capable of forming a DNA-binding complex with Pbx3. Rnx expression is unperturbed in Pbx3-deficient mice, but its ability to enhance transcription in vitro as a complex with TALE proteins is compromised in the absence of Pbx3. Thus, Pbx3 is essential for respiration and, like its DNA-binding partner Rnx, is critical for proper development of medullary respiratory control mechanisms. Pbx3-deficient mice provide a model for congenital central hypoventilation syndrome and suggest that Pbx3 mutations may promote the pathogenesis of this disorder. PMID:15466398
Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial.

PubMed

Argo, Curtis K; Patrie, James T; Lackner, Carolin; Henry, Thomas D; de Lange, Eduard E; Weltman, Arthur L; Shah, Neeral L; Al-Osaimi, Abdullah M; Pramoonjago, Patcharin; Jayakumar, Saumya; Binder, Lukas P; Simmons-Egolf, Winsor D; Burks, Sandra G; Bao, Yongde; Taylor, Ann Gill; Rodriguez, Jessica; Caldwell, Stephen H

2015-01-01

This study's aim was to assess the histological and metabolic effects of n-3 polyunsaturated fatty acids (PUFAs) vs. placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received n-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counselling on caloric intake and physical activity for all subjects. N-3- and placebo-treated groups showed no significant difference for the primary end point of NASH activity score (NAS) reduction ⩾ 2 points without fibrosis progression after adjustment for known covariates (n-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p = 0.99). Among subjects with increased or stable weight, n-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p = 0.014 for 2nd quartile, p = 0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on the paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. N-3 PUFAs at 3000 mg/day for one year did not lead to an improvement in the primary outcome of histological activity in NASH patients (⩾ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of n-3 therapy would lead to additional benefits is uncertain. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Higher n–6:n–3 Fatty Acid Intake Is Associated with Decreased Cardiometabolic Risk Factors in a Racially Diverse Sample of Children

PubMed Central

Crowe-White, Kristi M; Cardel, Michelle I; Burkhalter, Hannah H; Huo, Tianyao; Fernández, José R

2018-01-01

Abstract Background Accumulating evidence implicates diet quality in childhood as playing a significant role in adult cardiometabolic health. Polyunsaturated fatty acids (PUFAs) of the n–6 (ω-6) and n–3 (ω-3) series contribute unique protective effects against cardiometabolic disease. As such, the ratio between n–6 and n–3 PUFAs is a dietary metric of interest in the early life span, although an optimum intake ratio has yet to be determined. Objective This cross-sectional study assesses relations between the ratio of total n–6:n–3 PUFA intake and cardiometabolic risk factors in a racially diverse sample of children (n = 191) from the Admixture Mapping of Ethnic and Racial Insulin Complex Outcomes (AMERICO) study. Methods Outcome measures included waist circumference, lipid concentrations, fasting glucose, and two 24-h dietary recalls from boys and girls aged 7–12 y who self-reported as European American (n = 81), African American (n = 55), or Hispanic American (n = 55). Linear regression analyses were used to assess associations between predictors of interest and outcomes after adjusting for covariates. Results PUFA intake reflected in the n–6:n–3 ratio was inversely associated with concentrations of total and LDL cholesterol [β ± SE: −0.359 ± 0.107 (P = 0.001) and −0.189 ± 0.069 (P = 0.007), respectively]. Exploratory analyses showed that the intake of total n–6 PUFAs was not significantly predictive of any cardiometabolic risk factor assessed, whereas total n–3 PUFA intake was positively associated with concentrations of HDL cholesterol (β ± SE: 0.114 ± 0.042; P = 0.007). Conclusions Results suggest that the effect of n–6 and n–3 PUFA intake reflected in the ratio may be largely driven by n–3 PUFAs in reducing 2 lipid cardiometabolic risk factors among this multiethnic cohort of children. Until an ideal intake ratio is determined, nutritional counseling should focus on meeting recommended levels of
Increased F3-Isoprostanes in the Canadian Inuit Population Could Be Cardioprotective by Limiting F2-Isoprostane Production.

PubMed

Alkazemi, Dalal; Jackson, Robert L; Chan, Hing Man; Kubow, Stan

2016-09-01

F3-isoprostanes (F3-IsoPs), derived from peroxidation of eicosapentaenoic acid (C20:5n-3), could be cardioprotective by limiting production of F2-isoprostanes (F2-IsoPs), a cardiovascular disease risk factor. The objective of the study was to determine whether the n-3-polyunsaturated (PUFA)-rich Inuit diet is associated with a lower plasma ratio of F2-IsoPs to F3-IsoPs. This was a cross-sectional observational study. The study was conducted in 36 Canadian Arctic Inuit communities. Participants included a random subset (n = 233) of Inuit adults taken from a population-based survey. Plasma F2-IsoPs and F3-IsoPs, cardiometabolic risk factors (blood lipids, C-reactive protein, blood pressure, fasting glucose) and markers of dietary exposure (erythrocyte n-3 and n-6 PUFA, blood levels of Se, mercury, polychlorinated biphenyls) were measured. Inuit aged 40 years old and older vs younger Inuit showed higher concentrations of plasma F3-IsoPs and erythrocyte n-3 PUFA and lower plasma F2-IsoPs concentrations despite having higher blood lipids, fasting glucose, systolic blood pressure, and percentage body fat. Plasma F3-IsoPs were not associated with any cardiometabolic measures. When subjects were categorized into tertiles according to total n-3 PUFA erythrocyte concentrations, F3-IsoPs increased with increasing tertiles, whereas the F2-IsoP to F3-IsoP ratio was lowest at the highest n-3 tertile. The F2-IsoP to F3-IsoP ratio was significantly predicted by C20:5n-3 (β= -.365, P = .002); C20:4n-6:C20:5n-3 (β = .056, P = .006), blood mercury (β = -.812, P =.015), blood Se (β = -1.95, P = .015), and smoking (β = .745, P = .025). Plasma F3-IsoPs were not associated with cardiometabolic risk factors previously seen with F2-IsoPs. Higher n-3 fatty acid status was associated with lower plasma F2-IsoPs and higher plasma F3-IsoPs, which provides partial explanation to the cardioprotective effects of the n-3 PUFA-rich Inuit diet.
Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory drug-induced mucosal damage in the murine small intestine.

PubMed

Ueda, Toshihide; Hokari, Ryota; Higashiyama, Masaaki; Yasutake, Yuichi; Maruta, Koji; Kurihara, Chie; Tomita, Kengo; Komoto, Shunsuke; Okada, Yoshikiyo; Watanabe, Chikako; Usui, Shingo; Nagao, Shigeaki; Miura, Soichiro

2015-01-07

To investigate the effect of a fat rich diet on non-steroidal anti-inflammatory drug (NSAID)-induced mucosal damage in the murine small intestine. C57BL6 mice were fed 4 types of diets with or without indomethacin. One group was fed standard laboratory chow. The other groups were fed a fat diet consisting of 8% w/w fat, beef tallow (rich in SFA), fish oil, (rich in omega-3 PUFA), or safflower oil (rich in omega-6 PUFA). Indomethacin (3 mg/kg) was injected intraperitoneally from day 8 to day 10. On day 11, intestines and adhesions to submucosal microvessels were examined. In the indomethacin-treated groups, mucosal damage was exacerbated by diets containing beef tallow and fish oil, and was accompanied by leukocyte infiltration (P < 0.05). The mucosal damage induced by indomethacin was significantly lower in mice fed the safflower oil diet than in mice fed the beef tallow or fish oil diet (P < 0.05). Indomethacin increased monocyte and platelet migration to the intestinal mucosa, whereas safflower oil significantly decreased monocyte and platelet recruitment (P < 0.05). A diet rich in SFA and omega-3 PUFA exacerbated NSAID-induced small intestinal damage via increased leukocyte infiltration. Importantly, a diet rich in omega-6-PUFA did not aggravate inflammation as monocyte migration was blocked.
Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory drug-induced mucosal damage in the murine small intestine

PubMed Central

Ueda, Toshihide; Hokari, Ryota; Higashiyama, Masaaki; Yasutake, Yuichi; Maruta, Koji; Kurihara, Chie; Tomita, Kengo; Komoto, Shunsuke; Okada, Yoshikiyo; Watanabe, Chikako; Usui, Shingo; Nagao, Shigeaki; Miura, Soichiro

2015-01-01

AIM: To investigate the effect of a fat rich diet on non-steroidal anti-inflammatory drug (NSAID)-induced mucosal damage in the murine small intestine. METHODS: C57BL6 mice were fed 4 types of diets with or without indomethacin. One group was fed standard laboratory chow. The other groups were fed a fat diet consisting of 8% w/w fat, beef tallow (rich in SFA), fish oil, (rich in omega-3 PUFA), or safflower oil (rich in omega-6 PUFA). Indomethacin (3 mg/kg) was injected intraperitoneally from day 8 to day 10. On day 11, intestines and adhesions to submucosal microvessels were examined. RESULTS: In the indomethacin-treated groups, mucosal damage was exacerbated by diets containing beef tallow and fish oil, and was accompanied by leukocyte infiltration (P < 0.05). The mucosal damage induced by indomethacin was significantly lower in mice fed the safflower oil diet than in mice fed the beef tallow or fish oil diet (P < 0.05). Indomethacin increased monocyte and platelet migration to the intestinal mucosa, whereas safflower oil significantly decreased monocyte and platelet recruitment (P < 0.05). CONCLUSION: A diet rich in SFA and omega-3 PUFA exacerbated NSAID-induced small intestinal damage via increased leukocyte infiltration. Importantly, a diet rich in omega-6-PUFA did not aggravate inflammation as monocyte migration was blocked. PMID:25574090
Protective effects of n-6 fatty acids-enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A4 and its receptor

PubMed Central

Gobbetti, T; Ducheix, S; le Faouder, P; Perez, T; Riols, F; Boue, J; Bertrand-Michel, J; Dubourdeau, M; Guillou, H; Perretti, M; Vergnolle, N; Cenac, N

2015-01-01

Background and Purpose Long-term intake of dietary fatty acids is known to predispose to chronic inflammation, but their effects on acute intestinal ischaemia/reperfusion (I/R) injury is unknown. The aim of this study was to determine the consequences of a diet rich in n-3 or n-6 polyunsaturated fatty acids (PUFA) on intestinal I/R-induced damage. Experimental Approach Mice were fed three different isocaloric diets: a balanced diet used as a control and two different PUFA-enriched diets, providing either high levels of n-3 or of n-6 PUFA. Intestinal injury was evaluated after intestinal I/R. PUFA metabolites were quantitated in intestinal tissues by LC-MS/MS. Key Results In control diet-fed mice, intestinal I/R caused inflammation and increased COX and lipoxygenase-derived metabolites compared with sham-operated animals. Lipoxin A4 (LxA4) was significantly and selectively increased after ischaemia. Animals fed a high n-3 diet did not display a different inflammatory profile following intestinal I/R compared with control diet-fed animals. In contrast, intestinal inflammation was decreased in the I/R group fed with high n-6 diet and level of LxA4 was increased post-ischaemia compared with control diet-fed mice. Blockade of the LxA4 receptor (Fpr2), prevented the anti-inflammatory effects associated with the n-6 rich diet. Conclusions and Implications This study indicates that high levels of dietary n-6, but not n-3, PUFAs provides significant protection against intestinal I/R-induced damage and demonstrates that the endogenous production of LxA4 can be influenced by diet. PMID:25296998
Omega-3 Fatty Acid Supplementation is Associated With Oxidative Stress and Dyslipidemia, but Does not Contribute to Better Lipid and Oxidative Status on Hemodialysis Patients.

PubMed

de Mattos, Andresa Marques; da Costa, José Abrão Cardeal; Jordão Júnior, Alceu Afonso; Chiarello, Paula Garcia

2017-09-01

The aim of the study was to explore the effects of n-3 polyunsaturated fatty acids (PUFA) supplementation in physiological doses on oxidative stress (OS) and dyslipidemia in patients on hemodialysis (HD). Randomized, double-blind, controlled, experimental trial. A total of 88 HD patients ≥18 years old and on HD for at least 6 months. A total of 43 patients received 1.28 g/day of n-3 PUFA, and 45 other patients received soybean oil for 12 weeks. Both oil supplements were vitamin E standardized. Routine tests, lipid profile, advanced oxidation protein products, isoprostanes, vitamins C and E, total antioxidant capacity, serum fatty acids, and adverse effects were evaluated. Supplementation was not able to alter lipid or OS profiles. There was an increase in the serum n-3 PUFA levels (eicosapentaenoic acid: +116%; docosahexaenoic acid: +100%) and an improvement in the n-6/n-3 ratio (-49%) in the supplemented group. Associations between n-3 PUFA and improvement in isoprostane and advanced oxidation protein product and HDL were observed. Treatment was well tolerated. Although the n-3 PUFA supplementation was associated with lower concentrations of isoprostane and advanced oxidation protein product and higher HDL levels, it was not sufficient for the improvement of highly prevalent risk factors, such as OS and dyslipidemia in HD patients. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life.

PubMed

Alessandri, Jean-Marc; Guesnet, Philippe; Vancassel, Sylvie; Astorg, Pierre; Denis, Isabelle; Langelier, Bénédicte; Aïd, Sabah; Poumès-Ballihaut, Carine; Champeil-Potokar, Gaëlle; Lavialle, Monique

2004-01-01

Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are the major polyunsaturated fatty acids in the membranes of brain and retinal cells. Animals specifically deficient in dietary n-3 fatty acids have low DHA content in their membranes, reduced visual acuity and impaired learning ability. Studies on bottle-fed human infants have shown that adding DHA and AA to milk replacer-formulas can bring their concentrations in the infant blood lipids to values as high as those produced by breast-feeding and significantly improves mental development and maturation of visual function. In older subjects, diverse neuropsychiatric and neurodegenerative diseases have been associated to decreased blood levels of n-3 PUFA. Low intakes of fish or of n-3 PUFA in populations have been associated with increased risks of depression and Alzheimer disease, and n-3 PUFA, especially eicosapentaenoic acid (EPA, 20:5n-3), have shown efficacy as adjunctive treatment - and in some cases as the only treatment--in several psychiatric disorders. The mechanisms by which polyunsaturated fatty acids have an impact on neuronal functions will be reviewed: the modulation of membrane biophysical properties, regulation of neurotransmitter release, synthesis of biologically active oxygenated derivatives, and nuclear receptor-mediated transcription of genes responsive to fatty acids or to their derivatives.
Zinc deficiency promotes cystitis-related bladder pain by enhancing function and expression of Cav3.2 in mice.

PubMed

Ozaki, Tomoka; Matsuoka, Junki; Tsubota, Maho; Tomita, Shiori; Sekiguchi, Fumiko; Minami, Takeshi; Kawabata, Atsufumi

2018-01-15

Ca v 3.2 T-type Ca 2+ channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Ca v 3.2, and enhanced by H 2 S that interacts with zinc. Ca v 3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Ca v 3.2 activity by H 2 S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Ca v 3.2 function and/or expression. Dietary zinc deficiency for 2 weeks greatly decreased zinc concentrations in the plasma but not bladder tissue, and enhanced the bladder pain/referred hyperalgesia (BP/RH) following CPA at 200mg/kg, a subeffective dose, but not 400mg/kg, a maximal dose, an effect abolished by pharmacological blockade or gene silencing of Ca v 3.2. Acute zinc deficiency caused by systemic N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylendiamine (TPEN), a zinc chelator, mimicked the dietary zinc deficiency-induced Ca v 3.2-dependent promotion of BP/RH following CPA at 200mg/kg. CPA at 400mg/kg alone or TPEN plus CPA at 200mg/kg caused Ca v 3.2 overexpression accompanied by upregulation of Egr-1 and USP5, known to promote transcriptional expression and reduce proteasomal degradation of Ca v 3.2, respectively, in the dorsal root ganglia (DRG). The CSE inhibitor, β-cyano-l-alanine, prevented the BP/RH and upregulation of Ca v 3.2, Egr-1 and USP5 in DRG following TPEN plus CPA at 200mg/kg. Together, zinc deficiency promotes bladder pain accompanying CPA-induced cystitis by enhancing function and expression of Ca v 3.2 in nociceptors, suggesting a novel therapeutic avenue for treatment of bladder pain, such as zinc supplementation. Copyright © 2017 Elsevier B.V. All rights reserved.
Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OH)D3 metabolism.

PubMed

Mulligan, Jennifer K; Pasquini, Whitney N; Carroll, William W; Williamson, Tucker; Reaves, Nicholas; Patel, Kunal J; Mappus, Elliott; Schlosser, Rodney J; Atkinson, Carl

2017-01-01

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3
Polyunsaturated fatty acids and suicide risk in mood disorders: A systematic review.

PubMed

Pompili, Maurizio; Longo, Lucia; Dominici, Giovanni; Serafini, Gianluca; Lamis, Dorian A; Sarris, Jerome; Amore, Mario; Girardi, Paolo

2017-03-06

Deficiency of omega-3 polyunsaturated fatty acids (PUFAs) and an alteration between the ratio of omega-3 and omega-6 PUFAs may contribute to the pathogenesis of bipolar disorder and unipolar depression. Recent epidemiological studies have also demonstrated an association between the depletion of PUFAs and suicide. Our aim was to investigate the relationship between PUFAs and suicide; assess whether the depletion of PUFAs may be considered a risk factor for suicidal behavior; in addition to detailing the potential use of PUFAs in clinical practice. We performed a systematic review on PUFAs and suicide in mood disorders, searching MedLine, Excerpta Medica, PsycLit, PsycInfo, and Index Medicus for relevant epidemiological, post-mortem, and clinical studies from January 1997 to September 2016. A total of 20 articles from peer-reviewed journals were identified and selected for this review. The reviewed studies suggest that subjects with psychiatric conditions have a depletion of omega-3 PUFAs compared to control groups. This fatty acid depletion has also been found to contribute to suicidal thoughts and behavior in some cases. However, large epidemiological studies have generally not supported this finding, as the depletion of omega-3 PUFAs was not statistically different between controls and patients diagnosed with a mental illness and/or who engaged in suicidal behavior. Increasing PUFA intake may be relevant in the treatment of depression, however in respect to the prevention of suicide, the data is currently not supportive of this approach. Changes in levels of PUFAs may however be a risk factor to evaluate when assessing for suicide risk. Clinical studies should be conducted to prospectively assess whether prescriptive long-term use of PUFAs in PUFA-deficient people with depression, may have a preventative role in attenuating suicide. Copyright © 2016 Elsevier Inc. All rights reserved.
Long-chain n-3 polyunsaturated fatty acids and incidence rate of coronary artery calcification in Japanese in Japan and United States whites – population-based prospective cohort study

PubMed Central

Sekikawa, Akira; Miura, Katsuyuki; Lee, Sunghee; Fujiyoshi, Akira; Edmundowicz, Daniel; Kadowaki, Takashi; Evans, Rhobert W.; Kadowaki, Sayaka; Sutton-Tyrrell, Kim; Okamura, Tomonori; Bertolet, Marnie; Masaki, Kamal H.; Nakamura, Yasuyuki; Barinas-Mitchell, Emma J. M.; Willcox, Bradley J.; Kadota, Aya; Seto, Todd B.; Maegawa, Hiroshi; Kuller, Lewis H.; Ueshima, Hirotsugu

2014-01-01

Objective To determine whether serum levels of long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in incidence rate of coronary artery calcification (CAC) between Japanese in Japan and U.S. whites. Methods In a population-based prospective-cohort study, 214 Japanese and 152 white men aged 40–49 years at baseline (2002–2006) with coronary calcium score (CCS) = 0 were reexamined for CAC in 2007–2010. Among these, 175 Japanese and 113 whites participated in the follow-up exam. Incident cases were defined as participants with CCS ≥ 10 at follow-up. A relative risk regression analysis was used to model incidence rate ratio between Japanese and whites. The incidence rate ratio was first adjusted for potential confounders at baseline and then further adjusted for serum LCn3PUFAs at baseline. Results Mean (standard deviation) serum percentage of LCn3PUFA was > 100% higher in Japanese than in whites (9.08 (2.49) versus 3.84 (1.79), respectively, p<0.01). Japanese had a significantly lower incidence rate of CAC compared to whites (0.9 versus 2.9/100 person-years, respectively, p < 0.01). Incidence rate ratio of CAC taking follow-up time into account between Japanese and white men was 0.321 (95% confidence interval (CI) 0.150, 0.690: p<0.01). After adjusting for age, systolic-blood pressure, low-density-lipoprotein cholesterol, diabetes, and other potential confounders, the ratio remained significant: 0.262 (95% CI: 0.094, 0.731, p=0.01). After further adjusting for LCn3PUFAs, however, the ratio was attenuated and became non-significant (0.376 (95% CI: 0.090, 1.572, p=0.18). Conclusions LCn3PUFAs significantly contributed to the difference in CAC incidence between Japanese and white men. PMID:24352736

A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota.

PubMed

Watson, Henry; Mitra, Suparna; Croden, Fiona C; Taylor, Morag; Wood, Henry M; Perry, Sarah L; Spencer, Jade A; Quirke, Phil; Toogood, Giles J; Lawton, Clare L; Dye, Louise; Loadman, Paul M; Hull, Mark A

2017-09-26

Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). A randomised, open-label, cross-over trial of 8 weeks' treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week 'washout' period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium , Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. ISRCTN18662143. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless
PUFA diets alter the microRNA expression profiles in an inflammation rat model.

PubMed

Zheng, Zheng; Ge, Yinlin; Zhang, Jinyu; Xue, Meilan; Li, Quan; Lin, Dongliang; Ma, Wenhui

2015-06-01

Omega‑3 and ‑6 polyunsaturated fatty acids (PUFAs) can directly or indirectly regulate immune homeostasis via inflammatory pathways, and components of these pathways are crucial targets of microRNAs (miRNAs). However, no study has examined the changes in the miRNA transcriptome during PUFA‑regulated inflammatory processes. Here, we established PUFA diet‑induced autoimmune‑prone (AP) and autoimmune‑averse (AA) rat models, and studied their physical characteristics and immune status. Additionally, miRNA expression patterns in the rat models were compared using microarray assays and bioinformatic methods. A total of 54 miRNAs were differentially expressed in common between the AP and the AA rats, and the changes in rno‑miR‑19b‑3p, ‑146b‑5p and ‑183‑5p expression were validated using stem‑loop reverse transcription‑quantitative polymerase chain reaction. To better understand the mechanisms underlying PUFA‑regulated miRNA changes during inflammation, computational algorithms and biological databases were used to identify the target genes of the three validated miRNAs. Furthermore, Gene Ontology (GO) term annotation and KEGG pathway analyses of the miRNA targets further allowed to explore the potential implication of the miRNAs in inflammatory pathways. The predicted PUFA‑regulated inflammatory pathways included the Toll‑like receptor (TLR), T cell receptor (TCR), NOD‑like receptor (NLR), RIG‑I‑like receptor (RLR), mitogen‑activated protein kinase (MAPK) and the transforming growth factor‑β (TGF‑β) pathway. This study is the first report, to the best of our knowledge, on in vivo comparative profiling of miRNA transcriptomes in PUFA diet‑induced inflammatory rat models using a microarray approach. The results provide a useful resource for future investigation of the role of PUFA‑regulated miRNAs in immune homeostasis.
Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology.

PubMed

Layé, Sophie; Nadjar, Agnès; Joffre, Corinne; Bazinet, Richard P

2018-01-01

Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.
Identification and functional analysis of delta-9 desaturase, a key enzyme in PUFA Synthesis, isolated from the oleaginous diatom Fistulifera.

PubMed

Muto, Masaki; Kubota, Chihiro; Tanaka, Masayoshi; Satoh, Akira; Matsumoto, Mitsufumi; Yoshino, Tomoko; Tanaka, Tsuyoshi

2013-01-01

Oleaginous microalgae are one of the promising resource of nonedible biodiesel fuel (BDF) feed stock alternatives. Now a challenge task is the decrease of the long-chain polyunsaturated fatty acids (PUFAs) content affecting on the BDF oxidative stability by using gene manipulation techniques. However, only the limited knowledge has been available concerning the fatty acid and PUFA synthesis pathways in microalgae. Especially, the function of Δ9 desaturase, which is a key enzyme in PUFA synthesis pathway, has not been determined in diatom. In this study, 4 Δ(9) desaturase genes (fD9desA, fD9desB, fD9desC and fD9desD) from the oleaginous diatom Fistulifera were newly isolated and functionally characterized. The putative Δ(9) acyl-CoA desaturases in the endoplasmic reticulum (ER) showed 3 histidine clusters that are well-conserved motifs in the typical Δ(9) desaturase. Furthermore, the function of these Δ(9) desaturases was confirmed in the Saccharomyces cerevisiae ole1 gene deletion mutant (Δole1). All the putative Δ(9) acyl-CoA desaturases showed Δ(9) desaturation activity for C16∶0 fatty acids; fD9desA and fD9desB also showed desaturation activity for C18∶0 fatty acids. This study represents the first functional analysis of Δ(9) desaturases from oleaginous microalgae and from diatoms as the first enzyme to introduce a double bond in saturated fatty acids during PUFA synthesis. The findings will provide beneficial insights into applying metabolic engineering processes to suppressing PUFA synthesis in this oleaginous microalgal strain.
Co Relation between PUFA Index and Oral Health Related Quality of Life of a Rural Population in India: A Cross-Sectional Study.

PubMed

Praveen, Bhoopathi Haricharan; Prathibha, B; Reddy, P Parthasarthi; Monica, M; Samba, Amit; Rajesh, R

2015-01-01

A new measuring system called PUFA index had been identified to quantify the consequences of untreated dental caries. The co relation between PUFA index and oral health related quality of life has not been documented so far in India and thereby the need for this study Design: Cross-sectional observational study. Sample size of 212 subjects, who are the residents of a town in Rangareddy district were included to be a part of this study. The subjects were interviewed for the OHIP score and the clinical examination done to record the PUFA scores. The main objective of this study was to find out if there was any correlation between the OHIP scores and the study subjects and using the Pearson' s co relation coefficient, there was a significant correlation between the OHIP and the PUFA scores.(Pearson' s correlation= 0.31) CONCLUSION: The mean OHIP and PUFA scores of the study subjects were 2.21 and 0.40 respectively. There is a positive correlation between the OHIP score and the PUFA score among the study population i.e. with the PUFA scores increasing, it has a detrimental effect on the oral health related quality of life of the individual.
Omega-3 Fatty Acid Deficiency Augments Risperidone-Induced Hepatic Steatosis in Rats: Positive Association with Stearoyl-CoA Desaturase

PubMed Central

McNamara, Robert K.; Magrisso, I. Jack; Hofacer, Rylon; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Benoit, Stephen C.

2012-01-01

Psychiatric patients frequently exhibit long-chain n-3 (LCn-3) fatty acid deficits and elevated triglyceride (TAG) production following chronic exposure to second generation antipsychotics (SGA). Emerging evidence suggests that SGAs and LCn-3 fatty acids have opposing effects on stearoyl-CoA desaturase-1 (SCD1), which plays a pivotal role in TAG biosynthesis. Here we evaluated whether low LCn-3 fatty acid status would augment elevations in rat liver and plasma TAG concentrations following chronic treatment with the SGA risperidone (RSP), and evaluated relationships with hepatic SCD1 expression and activity indices. In rats maintained on the n-3 fatty acid-fortified (control) diet, chronic RSP treatment significantly increased liver SCD1 mRNA and activity indices (18:1/18:0 and 16:1/16:0 ratios), and significantly increased liver, but not plasma, TAG concentrations. Rats maintained on the n-3 deficient diet exhibited significantly lower liver and erythrocyte LCn-3 fatty acid levels, and associated elevations in LCn-6/LCn-3 ratio. In n-3 deficient rats, RSP-induced elevations in liver SCD1 mRNA and activity indices (18:1/18:0 and 16:1/16:0 ratios) and liver and plasma TAG concentrations were significantly greater than those observed in RSP-treated controls. Plasma glucose levels were not altered by diet or RSP, and body weight was lower in RSP- and VEH-treated n-3 deficient rats. These preclinical data support the hypothesis that low n-3 fatty acid status exacerbates RSP-induced hepatic steatosis by augmenting SCD1 expression and activity. PMID:22750665
Dietary supplementation with arachidonic acid but not eicosapentaenoic or docosahexaenoic acids alter lipids metabolism in C57BL/6J mice.

PubMed

Magdeldin, Sameh; Elewa, Yaser; Ikeda, Takako; Ikei, Junko; Zhang, Ying; Xu, Bo; Nameta, Masaaki; Fujinaka, Hidehiko; Yoshida, Yutaka; Yaoita, Eishin; Yamamoto, Tadashi

2009-09-01

In order to investigate the effects of dietary supplementation rich in omega 3 and omega 6 fatty acids, we set up an experiment of twenty four C57BL/6J male mice segregated into 3 groups: normal diet (ND), omega 3 polyunsaturated fatty acid (n-3 PUFA,) and omega 6 (n-6 PUFA). At the end of the experiment that lasted for 1 month, food consumption of ND and n-3 PUFA were similar while it decreased in n-6 PUFA group. Total cholesterol, triglycerides, free fatty acids, and phospholipids profiles were increased in n-6 PUFA. LDL decreased in n-3 PUFA while increased in n-6 PUFA fed mice comparing to control group. On the other hand, there was no difference between treatments in HDL and glucose levels. Expression of leptin (ob) gene transcripts in epididymal fat were significantly elevated in n-6 PUFA mice compared to ND and n-3 PUFA groups while hypothalamic ob receptor A (obRa) mRNA did not changed in response to diet regimes. Transmission and scanning electron microscopy showed different degrees in fatty changes in the liver of both PUFA groups including lipid droplet infiltration and Ito cells with over accumulated lipids. In conclusion, under PUFA dietary supplementation, the hyperlipidemic status and elevated ob expression of n-6 PUFA but not n-3 PUFA fed mice suggests altered lipid metabolism between PUFA groups and/or different endocrine involvement. Moreover, the coincidently structural changes observed in liver of this group direct us to call for further studies to investigate the anti-obesity effect and safety of these PUFA under high supplementation condition.
Omega-3 fatty acid supplementation and cardiovascular disease

PubMed Central

Jump, Donald B.; Depner, Christopher M.; Tripathy, Sasmita

2012-01-01

Epidemiological studies on Greenland Inuits in the 1970s and subsequent human studies have established an inverse relationship between the ingestion of omega-3 fatty acids [C20–22 ω 3 polyunsaturated fatty acids (PUFA)], blood levels of C20–22 ω 3 PUFA, and mortality associated with cardiovascular disease (CVD). C20–22 ω 3 PUFA have pleiotropic effects on cell function and regulate multiple pathways controlling blood lipids, inflammatory factors, and cellular events in cardiomyocytes and vascular endothelial cells. The hypolipemic, anti-inflammatory, anti-arrhythmic properties of these fatty acids confer cardioprotection. Accordingly, national heart associations and government agencies have recommended increased consumption of fatty fish or ω 3 PUFA supplements to prevent CVD. In addition to fatty fish, sources of ω 3 PUFA are available from plants, algae, and yeast. A key question examined in this review is whether nonfish sources of ω 3 PUFA are as effective as fatty fish-derived C20–22 ω 3 PUFA at managing risk factors linked to CVD. We focused on ω 3 PUFA metabolism and the capacity of ω 3 PUFA supplements to regulate key cellular events linked to CVD. The outcome of our analysis reveals that nonfish sources of ω 3 PUFA vary in their capacity to regulate blood levels of C20–22 ω 3 PUFA and CVD risk factors. PMID:22904344
Omega-3 fatty acids are inversely related to callous and unemotional traits in adolescent boys with attention deficit hyperactivity disorder.

PubMed

Gow, Rachel V; Vallee-Tourangeau, Frederic; Crawford, Michael Angus; Taylor, Eric; Ghebremeskel, Kebreab; Bueno, Allain A; Hibbeln, Joseph R; Sumich, Alexander; Rubia, Katya

2013-06-01

A number of research studies have reported abnormal plasma fatty acid profiles in children with ADHD along with some benefit of n-3 to symptoms of ADHD. However, it is currently unclear whether (lower) long chain-polyunsaturated fatty acids (LC-PUFAs) are related to ADHD pathology or to associated behaviours. The aim of this study was to test whether (1) ADHD children have abnormal plasma LC-PUFA levels and (2) ADHD symptoms and associated behaviours are correlated with LC-PUFA levels. Seventy-two, male children with (n=29) and without a clinical diagnosis of ADHD (n=43) were compared in their plasma levels of LC-PUFA. Plasma DHA was higher in the control group prior to statistical correction. Callous-unemotional (CU) traits were found to be significantly negatively related to both eicosapentaenoic acid (EPA), and total omega-3 in the ADHD group. The findings unveil for the first time that CU and anti-social traits in ADHD are associated with lower omega-3 levels. Copyright © 2013 Elsevier Ltd. All rights reserved.
Co Relation between PUFA Index and Oral Health Related Quality of Life of a Rural Population in India: A Cross-Sectional Study

PubMed Central

Prathibha, B.; Reddy, P. Parthasarthi; Monica, M.; Samba, Amit; Rajesh, R.

2015-01-01

Introduction: A new measuring system called PUFA index had been identified to quantify the consequences of untreated dental caries. The co relation between PUFA index and oral health related quality of life has not been documented so far in India and thereby the need for this study Design: Cross-sectional observational study. Materials and Methods: Sample size of 212 subjects, who are the residents of a town in Rangareddy district were included to be a part of this study. The subjects were interviewed for the OHIP score and the clinical examination done to record the PUFA scores. Results: The main objective of this study was to find out if there was any correlation between the OHIP scores and the study subjects and using the Pearson’ s co relation coefficient, there was a significant correlation between the OHIP and the PUFA scores.(Pearson’ s correlation= 0.31) Conclusion: The mean OHIP and PUFA scores of the study subjects were 2.21 and 0.40 respectively. There is a positive correlation between the OHIP score and the PUFA score among the study population i.e. with the PUFA scores increasing, it has a detrimental effect on the oral health related quality of life of the individual. PMID:25738084
Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system.

PubMed

Ren, Huixia; Luo, Chuanming; Feng, Yanqing; Yao, Xiaoli; Shi, Zhe; Liang, Fengyin; Kang, Jing X; Wan, Jian-Bo; Pei, Zhong; Su, Huanxing

2017-01-01

Impairment of amyloid-β (Aβ) clearance leads to Aβ accumulation in the brain during the development of Alzheimer's disease (AD). Strategies that can restore or improve the clearance function hold great promise in delaying or preventing the onset of AD. Here, we show that n-3 polyunsaturated fatty acids (PUFAs), by use of fat-1 transgenic mice and oral administration of fish oil, significantly promote interstitial Aβ clearance from the brain and resist Aβ injury. Such beneficial effects were abolished in Aqp4-knockout mice, suggesting that the AQP4-dependent glymphatic system is actively involved in the promoting the effects of n-3 PUFAs on the clearance of extracellular Aβ. Imaging on clarified brain tissues clearly displayed that n-3 PUFAs markedly inhibit the activation of astrocytes and protect the AQP4 polarization in the affected brain region after Aβ injection. The results of the present study prove a novel mechanism by which n-3 PUFAs exert protective roles in reducing Aβ accumulation via mediating the glymphatic system function.-Ren, H., Luo, C., Feng, Y., Yao, X., Shi, Z., Liang, F., Kang, J. X., Wan, J.-B., Pei, Z., Su, H. Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system. © FASEB.
Postnatal fish oil supplementation in high-risk infants to prevent allergy: randomized controlled trial.

PubMed

D'Vaz, N; Meldrum, S J; Dunstan, J A; Martino, D; McCarthy, S; Metcalfe, J; Tulic, M K; Mori, T A; Prescott, S L

2012-10-01

Relative deficiency of dietary omega 3 polyunsaturated fatty acids (n-3 PUFA) has been implicated in the rising allergy prevalence in Westernized countries. Fish oil supplementation may provide an intervention strategy for primary allergy prevention. The objective of this study was to assess the effect of fish oil n-3 PUFA supplementation from birth to 6 months of age on infant allergic disease. In a double-blind randomized controlled trial, 420 infants at high atopic risk received a daily supplement of fish oil containing 280 mg docosahexaenoic acid and 110 mg eicosapentaenoic acid or a control (olive oil), from birth to age 6 months. PUFA levels were measured in 6-month-old infants' erythrocytes and plasma and their mothers' breast milk. Eczema, food allergy, asthma and sensitization were assessed in 323 infants for whom clinical follow-up was completed at 12 months of age. At 6 months of age, infant docosahexaenoic acid and eicosapentaenoic acid levels were significantly higher (both P < .05) and erythrocyte arachidonic acid levels were lower (P = .003) in the fish oil group. Although n-3 PUFA levels at 6 months were associated with lower risk of eczema (P = .033) and recurrent wheeze (P = .027), the association with eczema was not significant after multiple comparisons and there was no effect of the intervention per se on the primary study outcomes. Specifically, between-group comparisons revealed no differences in the occurrence of allergic outcomes including sensitization, eczema, asthma, or food allergy. Postnatal fish oil supplementation improved infant n-3 status but did not prevent childhood allergic disease.
Diagnosis and management of trimethylaminuria (FMO3 deficiency) in children.

PubMed

Chalmers, R A; Bain, M D; Michelakakis, H; Zschocke, J; Iles, R A

2006-02-01

Persistent trimethylaminuria in children is caused by autosomal recessively inherited impairment of hepatic trimethylamine (TMA) oxidation due to deficiency of flavin monooxygenase 3 (FMO3) secondary to mutations in the FMO3 gene. Trimethylaminuria or 'fish odour syndrome' is due to excessive excretion into body fluids and breath of TMA derived from the enterobacterial metabolism of dietary precursors. The disorder is present from birth but becomes apparent as foods containing high amounts of choline or of trimethylamine N-oxide (TMAO) from marine (sea or saltwater) fish are introduced into the diet. In our experience, trimethylaminuria (FMO3 deficiency) in children is rare. We have compared the dynamics and diagnostic efficacy of choline loading with marine fish meals in six children with trimethylaminuria. Loading with a marine fish meal provides a simple and acceptable method for confirmation of diagnosis of suspected trimethylaminuria in children, with the effects being cleared more quickly than with a choline load test. However, oral loading with choline bitartrate allows estimation of residual oxidative capacity in vivo and is a useful adjunct to molecular studies. Patients homozygous for the 'common' P153L mutation in the FMO3 gene showed virtual complete lack of residual TMA N-oxidative capacity, consistent with a nonfunctional or absent FMO3 enzyme, whereas a patient with the M82T mutation showed some residual oxidative capacity. A patient compound heterozygous for two novel mutations, G193E and R483T, showed considerable residual N-oxidative capacity. A further patient, heterozygous for two novel sequence variations in the FMO3 gene, consistently showed malodour and elevated urinary TMA/TMAO ratios under basal conditions but a negative response to both choline and marine fish meal loading. Comparison of the effects of administration of antibiotics (metronidazole, amoxicillin, neomycin) on gut bacterial production of trimethylamine from choline showed they
Food sources and intake of n-6 and n-3 fatty acids in low-income countries with emphasis on infants, young children (6-24 months), and pregnant and lactating women.

PubMed

Michaelsen, Kim F; Dewey, Kathryn G; Perez-Exposito, Ana B; Nurhasan, Mulia; Lauritzen, Lotte; Roos, Nanna

2011-04-01

With increasing interest in the potential effects of n-6 and n-3 fatty acids in early life, there is a need for data on the dietary intake of polyunsaturated fatty acids (PUFA) in low-income countries. This review compiles information on the content in breast milk and in foods that are important in the diets of low-income countries from the few studies available. We also estimate the availability of fat and fatty acids in 13 low-income and middle-income countries based on national food balance sheets from the United Nations' Food and Agriculture Organization Statistical Database (FOASTAT). Breast milk docosahexaenoic acid content is very low in populations living mainly on a plant-based diet, but higher in fish-eating countries. Per capita supply of fat and n-3 fatty acids increases markedly with increasing gross domestic product (GDP). In most of the 13 countries, 70-80% of the supply of PUFA comes from cereals and vegetable oils, some of which have very low α-linolenic acid (ALA) content. The total n-3 fatty acid supply is below or close to the lower end of the recommended intake range [0.4%E (percentage of energy supply)] for infants and young children, and below the minimum recommended level (0.5%E) for pregnant and lactating women in the nine countries with the lowest GDP. Fish is important as a source of long-chain n-3 fatty acids, but intake is low in many countries. The supply of n-3 fatty acids can be increased by using vegetable oils with higher ALA content (e.g. soybean or rapeseed oil) and by increasing fish production (e.g. through fish farming). © 2011 Blackwell Publishing Ltd.
Beneficial effects of ω-3 PUFA in children on cardiovascular risk factors during childhood and adolescence.

PubMed

Bonafini, Sara; Antoniazzi, Franco; Maffeis, Claudio; Minuz, Pietro; Fava, Cristiano

2015-07-01

Omega-3 polyunsatured fatty acids (ω-3 PUFA) are essential nutrients mainly derived from fish and seafood but present also in vegetables such as nuts and seed-oils. Some epidemiological and clinical studies indicate a protection of ω-3 FA against cardiovascular disease and a favourable effect on cardiovascular risk factors control in adults. The evidences of their effects in children and adolescents are scanty but a possible beneficial role, especially for insulin sensitivity and blood pressure control, has been proposed. In this review we want to focus especially on the evidences, which could justify the assumption of ω-3 in children and adolescents, and to underline the aspects which need further investigation. Mechanisms through which ω-3 FA act are manifolds and still a matter of investigation: beside their interaction with ion channel and their influence on plasma membrane fluidity, probably the main effect is acting as competitor for cytochrome P-450 (CYP) with respect to ω-6 FA. Thus, they can modulate the biosynthesis of eicosanoids and other lipid mediators, which likely exert a protective action. Another suggestive hypothesis is that their beneficial effect is not dependent only on the intake of ω-3 FA, but also on the complex interaction between different nutrients including ω-3 and other FAs with polymorphisms in genes involved in ω-3 FA modulation. This complex interaction has seldom been explored in children and adolescents. Further studies are needed to investigate all these points in order to find a better collocation of ω-3 FA on the available armamentarium for preventive, possibly individualized, medicine. Copyright © 2015 Elsevier Inc. All rights reserved.
Effect of selenium deficiency on the thermoelectric properties of n -type In 4 Se 3 - x compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, G. H.; Lan, Y. C.; Wang, H.

2011-03-01

Thermoelectric properties of dense bulk polycrystalline In 4 Se 3 - x ( x = 0, 0.25, 0.5, 0.65, and 0.8) compounds are investigated. A peak dimensionless thermoelectric figure of merit ( ZT ) of about 1 is achieved for x = 0.65 and 0.8. The peak ZT is about 50% higher than the previously reported highest value for polycrystalline In 4 Se 3 - x compounds. Our In 4 Se 3 - x samples were prepared by ball milling and hot pressing. We show that it is possible to effectively control the electrical conductivity and thermal conductivity by controllingmore » selenium (Se) deficiency x . The ZT enhancement is mainly attributed to the thermal conductivity reduction due to the increased phonon scattering by Se deficiency, defects, and nanoscale inclusions in the ball-milled and hot-pressed dense bulk In 4 Se 3 - x samples.« less
Effect of selenium deficiency on the thermoelectric properties of n-type In 4Se 3-x compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, G H; Lan, Y C; Wang, H

2011-03-04

Thermoelectric properties of dense bulk polycrystalline In 4Se 3-x (x = 0, 0.25, 0.5, 0.65, and 0.8) compounds are investigated. A peak dimensionless thermoelectric figure of merit (ZT) of about 1 is achieved for x = 0.65 and 0.8. The peak ZT is about 50% higher than the previously reported highest value for polycrystalline In 4Se 3-x} compounds. Our In 4Se 3-x samples were prepared by ball milling and hot pressing. We show that it is possible to effectively control the electrical conductivity and thermal conductivity by controlling selenium (Se) deficiency x. The ZT enhancement is mainly attributed to themore » thermal conductivity reduction due to the increased phonon scattering by Se deficiency, defects, and nanoscale inclusions in the ball-milled and hot-pressed dense bulk In 4Se 3-x samples.« less
Differential response to an algae supplement high in DHA mediated by maternal periconceptional diet: intergenerational effects of n-6 fatty acids.

PubMed

Clayton, Edward H; Lamb, Tracy A; Refshauge, Gordon; Kerr, Matthew J; Bailes, Kristy L; Ponnampalam, Eric N; Friend, Michael A; Hopkins, David L

2014-08-01

Algae high in docosahexaenoic acid (DHA) may provide a source of long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) for inclusion in the diet of lambs to improve the LCn-3PUFA status of meat. The effect of background LCn-3PUFA status on the metabolism of high DHA algae is, however, unknown. The aim of the current study was to determine whether the response to a high in DHA algae supplement fed to lambs for six weeks prior to slaughter was mediated by a maternal periconceptional diet. Forty Poll Dorset × Border Leicester × Merino weaner lambs were allocated to receive either a ration based on oat grain, lupin grain, and chopped lucerne (control) or the control ration with DHA-Gold™ algae included at 1.92 % DM (Algae) based on whether the dams of lambs had previously been fed a diet high in n-3 or n-6 around conception. LCn-3PUFA concentration was determined in plasma and red blood cells (RBC) prior to and following feeding. The concentrations of EPA and DHA in the plasma and RBC of lambs receiving the control ration were significantly (p < 0.001) lower when lambs received the ration for 14 days compared with pre-feeding concentrations. The concentrations of EPA and DHA were also significantly (p < 0.001) higher when lambs consumed the Algae ration compared with the control ration for 42 days. The increase in EPA and DHA was, however, significantly (p < 0.05) lower if lamb dams had previously been fed a diet high in n-6 at conception. Assessing the previous nutrition and n-3 status of lambs may allow producers to more accurately predict the likely response to supplements high in LCn-3PUFA, particularly, DHA.
Polymorphisms in genes involved in the triglyceride synthesis pathway and marine omega-3 polyunsaturated fatty acid supplementation modulate plasma triglyceride levels.

PubMed

Ouellette, Catherine; Cormier, Hubert; Rudkowska, Iwona; Guénard, Frédéric; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2013-01-01

Marine omega-3 (n-3) polyunsaturated fatty acids (PUFA) reduce plasma triglyceride (TG) levels. Genetic factors such as single nucleotide polymorphisms (SNPs) could be responsible for the variability of the plasma TG response to n-3 PUFA supplementation. Previous studies have demonstrated that n-3 PUFA supplementation using fish oil modified the expression levels of three genes involved in the TG synthesis pathway (GPAM, AGPAT3 and AGPAT4) in peripheral blood mononuclear cells. A total of 210 subjects consumed 5 g/day of a fish oil supplement for 6 weeks. Plasma lipids were measured before and after the supplementation period. Three SNPs in GPAM, 13 SNPs in AGPAT3 and 35 SNPs in AGPAT4 were genotyped. In an ANOVA for repeated measures adjusted for age, sex and BMI, genotype effects on plasma TG levels were observed for rs1838452 in AGPAT3 as well as for rs746731 and rs2293286 in AGPAT4. Genotype × supplementation interaction effects on plasma TG levels were observed for rs2792751 and rs17129561 in GPAM as well as for rs3798943 and rs9458172 in AGPAT4 (p < 0.05). These results suggest that SNPs in genes involved in the TG synthesis pathway may influence plasma TG levels after n-3 PUFA supplementation. © 2014 S. Karger AG, Basel.
Comparative study of tissue deposition of omega-3 fatty acids from polar-lipid rich oil of the microalgae Nannochloropsis oculata with krill oil in rats.

PubMed

Kagan, Michael L; Levy, Aharon; Leikin-Frenkel, Alicia

2015-01-01

Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) exert health benefits which are dependent upon their incorporation into blood, cells and tissues. Plasma and tissue deposition of LC n-3 PUFA from oils extracted from the micro-algae Nannochloropsis oculata and from krill were compared in rats. The algal oil provides eicosapentaenoic acid (EPA) partly conjugated (15%) to phospholipids and glycolipids but no docosahexaenoic acid (DHA), whereas krill oil provides both EPA and DHA conjugated in part (40%) to phospholipids. Rats fed a standard diet received either krill oil or polar-lipid rich algal oil by gavage daily for 7 days (5 ml oil per kg body weight each day). Fatty acid concentrations were analyzed in plasma, brain and liver, and two adipose depots since these represent transport, functional and storage pools of fatty acids, respectively. When measuring total LC n-3 PUFA (sum of EPA, docosapentaenoic acid (DPA) and DHA), there was no statistically significant difference between the algal oil and krill oil for plasma, brain, liver and gonadal adipose tissue. Concentrations of LC n-3 PUFA were higher in the retroperitoneal adipose tissue from the algal oil group. Tissue uptake of LC n-3 PUFA from an algal oil containing 15% polar lipids (glycolipids and phospholipids) was found to be equivalent to krill oil containing 40% phospholipids. This may be due to glycolipids forming smaller micelles during ingestive hydrolysis than phospholipids. Ingestion of fatty acids with glycolipids may improve bioavailability, but this needs to be further explored.

Supplementation with N-3 Long-Chain Polyunsaturated Fatty Acids or Olive Oil in Men and Women with Renal Disease Induces Differential Changes in the DNA Methylation of FADS2 and ELOVL5 in Peripheral Blood Mononuclear Cells

PubMed Central

Hoile, Samuel P.; Clarke-Harris, Rebecca; Huang, Rae-Chi; Calder, Philip C.; Mori, Trevor A.; Beilin, Lawrence J.; Lillycrop, Karen A.; Burdge, Graham C.

2014-01-01

Background Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans. Methods and Results We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5′ regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (>10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (>10%) 1/12 ELOVL5 CpGs in men. OO altered (>6%) 8/22 FADS2 CpGs and (>3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (>5%) 3/22 FADS2 CpGs and 2/12 (>3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts. Conclusions These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function. PMID:25329159
Different Dietary Protein and PUFA Interventions Alter the Fatty Acid Concentrations, but Not the Meat Quality, of Porcine Muscle

PubMed Central

Dannenberger, Dirk; Nuernberg, Karin; Nuernberg, Gerd; Priepke, Antje

2012-01-01

The present study investigated the effect of a reduced protein diet in combination with different vegetable oils (sunflower seed oil or linseed oil) on carcass traits, meat quality and fatty acid profile in porcine muscle. Forty male Landrace pigs were allocated into four experimental groups (each n = 8) and one control group (n = 8) at a live weight of approximately 60 kg. The pigs were fed ad libitum from 60 kg to 100 kg live weight and restricted to 2.8 kg/day until they reached 120 kg. In contrast to other studies, the intramuscular fat content (IMF) did not increase in animals of groups fed a reduced protein diet and vegetable oils. The IMF ranged between 1.2% and 1.4%. The growth performance and meat quality of the longissimus muscle was not affected by the diet, but the average daily gain (ADG) and drip loss were affected. The muscle fatty acid concentrations were significantly affected by the diet, resulting in higher n-3 FA concentrations up to 113 mg/100 g muscle and lower n-6/n-3 PUFA ratio for pigs fed linseed oil-containing high- and reduced protein diets, compared to sunflower seed oil-containing diets. PMID:23112912
Lecithin derived from ω-3 PUFA fortified eggs decreases blood pressure in spontaneously hypertensive rats.

PubMed

Nowacki, Dorian; Martynowicz, Helena; Skoczyńska, Anna; Wojakowska, Anna; Turczyn, Barbara; Bobak, Łukasz; Trziszka, Tadeusz; Szuba, Andrzej

2017-09-28

Hypertension is the most common risk factor for stroke, coronary heart disease and heart failure, which are the leading causes of death worldwide. Dietary patterns and supplements intakes are becoming important factors in the hypertension. The aim of this study was to estimate the effects of new generation egg yolk phospholipids rich in lecithin (SL) esterified with omega-3 and omega-6 fatty acids on blood pressure in hypertensive rats (SHR). Here we have reported that lecithin (SL) derived from egg yolk lowers blood pressure in pathology of hypertension. The SHR rats treated with SL had significantly lower blood pressure than control group (157/104 vs. 178/121 mmHg; P < 0.05) and down-regulated mesenteric artery over-response to norepinephrine and potassium chloride, giving similar arterial response as for normotensive Wistar Kyoto rats (WKY). Hypertensive rats treated by SL demonstrated significantly lower serum level of inflammatory factors. This work also indicates that SL treatment lowers heart rate and reduces the serum level of oxidative stress marker - nitrotyrosine - by 30-34% in both hypertensive and normotensive animals. Phospholipids with lecithin derived from PUFA fortified eggs may be a valuable dietary supplement in prophylaxis of hypertension and in patients with hypertension, however, this requires further studies on humans.
A novel omega3-fatty acid desaturase involved in the biosynthesis of eicosapentaenoic acid.

PubMed Central

Pereira, Suzette L; Huang, Yung-Sheng; Bobik, Emil G; Kinney, Anthony J; Stecca, Kevin L; Packer, Jeremy C L; Mukerji, Pradip

2004-01-01

Long-chain n-3 PUFAs (polyunsaturated fatty acids) such as EPA (eicosapentaenoic acid; 20:5 n-3) have important therapeutic and nutritional benefits in humans. In plants, cyanobacteria and nematodes, omega3-desaturases catalyse the formation of these n-3 fatty acids from n-6 fatty acid precursors. Here we describe the isolation and characterization of a gene ( sdd17 ) derived from an EPA-rich fungus, Saprolegnia diclina, that encodes a novel omega3-desaturase. This gene was isolated by PCR amplification of an S. diclina cDNA library using oligonucleotide primers corresponding to conserved regions of known omega3-desaturases. Expression of this gene in Saccharomyces cerevisiae, in the presence of various fatty acid substrates, revealed that the recombinant protein could exclusively desaturate 20-carbon n-6 fatty acid substrates with a distinct preference for ARA (arachidonic acid; 20:4 n-6), converting it into EPA. This activity differs from that of the known omega3-desaturases from any organism. Plant and cyanobacterial omega3-desaturases exclusively desaturate 18-carbon n-6 PUFAs, and a Caenorhabditis elegans omega3-desaturase preferentially desaturated 18-carbon PUFAs over 20-carbon substrates, and could not convert ARA into EPA when expressed in yeast. The sdd17 -encoded desaturase was also functional in transgenic somatic soya bean embryos, resulting in the production of EPA from exogenously supplied ARA, thus demonstrating its potential for use in the production of EPA in transgenic oilseed crops. PMID:14651475
The older people, omega-3, and cognitive health (EPOCH) trial design and methodology: A randomised, double-blind, controlled trial investigating the effect of long-chain omega-3 fatty acids on cognitive ageing and wellbeing in cognitively healthy older adults

PubMed Central

2011-01-01

Background Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and better cognitive outcomes in older adults. To date, only two randomised, controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy populations. Of these trials only one found a benefit, in the subgroup carrying the ApoE-ε4 allele. The benefits of n-3 LC PUFA supplementation on cognitive function in older normal populations thus still remain unclear. The main objective of the current study was to provide a comprehensive assessment of the potential of n-3 LC PUFAs to slow cognitive decline in normal elderly people, and included ApoE-ε4 allele carriage as a potential moderating factor. The detailed methodology of the trial is reported herein. Methods The study was a parallel, 18-month, randomised, double-blind, placebo-controlled intervention with assessment at baseline and repeated 6-monthly. Participants (N = 391, 53.7% female) aged 65-90 years, English-speaking and with normal cognitive function, were recruited from metropolitan Adelaide, South Australia. Participants in the intervention arm received capsules containing fish-oil at a daily dosage of 1720 mg of docosahexaenoic acid and 600 mg of eicosapentaenoic acid while the placebo arm received the equivalent amount of olive oil in their capsules. The primary outcome is rate of change in cognitive performance, as measured by latent variables for the cognitive constructs (encompassing Reasoning, Working Memory, Short-term Memory, Retrieval Fluency, Inhibition, Simple and Choice-Reaction Time, Perceptual Speed, Odd-man-out Reaction Time, Speed of Memory Scanning, and Psychomotor Speed) and assessed by latent growth curve modeling. Secondary outcomes are change in the Mini-mental State Examination, functional capacity and well-being (including health status, depression, mood, and self-report cognitive functioning), blood
Involvement of Smad3 phosphoisoform-mediated signaling in the development of colonic cancer in IL-10-deficient mice.

PubMed

Hachimine, Daisaku; Uchida, Kazushige; Asada, Masanori; Nishio, Akiyoshi; Kawamata, Seiji; Sekimoto, Go; Murata, Miki; Yamagata, Hideo; Yoshida, Katsunori; Mori, Shigeo; Tahashi, Yoshiya; Matsuzaki, Koichi; Okazaki, Kazuichi

2008-06-01

Chronic inflammation predisposes to cancer. Transforming growth factor (TGF)-beta, a multifunctional protein, suppresses the growth of normal colonic epithelial cells, whereas it stimulates the proliferation of cancer cells. Interleukin (IL)-10-deficient mice, which develop colitis and colorectal cancer, show an increased level of plasma TGF-beta. Although TGF-beta may be a key molecule in the development of colon cancer arising from chronic colitis in IL-10-deficient mice, the role of TGF-beta still remains unclear. TGF-beta activates not only TGF-beta type I receptor (TbetaRI) but also c-Jun N-terminal kinase (JNK), which converts the mediator Smad3 into two distinctive phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). We studied C57BL/6-IL-10-deficient mice (n=18) at 4 to 32 weeks of age. We investigated histology, and pSmad2/3L, pSmad2/3C, and p53 by immunohistochemistry. pSmad3L staining was detected in the cancer cells in all 10 mice with colonic cancer and in the epithelial cells in 7 of 12 mice with colonic dysplasia, but not in the normal or colitic mice. pSmad3c was detected without any significant difference between stages. p53 was weakly stained in a few cancer cells in 5 out of 10 mice. Smad3L signaling plays an important role in the carcinogenesis of chronic colitis in IL-10-deficient mice.
Cloning and Characterization of Lxr and Srebp1, and Their Potential Roles in Regulation of LC-PUFA Biosynthesis in Rabbitfish Siganus canaliculatus.

PubMed

Zhang, Qinghao; You, Cuihong; Liu, Fang; Zhu, Wendi; Wang, Shuqi; Xie, Dizhi; Monroig, Óscar; Tocher, Douglas R; Li, Yuanyou

2016-09-01

Rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to have the ability to biosynthesize C20-22 long-chain polyunsaturated fatty acid (LC-PUFA) from C18 PUFA precursors, which is generally absent or low in marine teleosts. Thus, understanding the molecular basis of LC-PUFA biosynthesis in rabbitfish will contribute to efforts aimed at optimizing LC-PUFA biosynthesis in teleosts, especially marine species. In the present study, the importance of the transcription factors liver X receptor (Lxr) and sterol regulatory element-binding protein 1 (Srebp1) in regulation of LC-PUFA biosynthesis in rabbitfish was investigated. First, full-length cDNA of Lxr and Srebp1 were cloned and characterized. The Lxr mRNA displayed a ubiquitous tissue expression pattern while Srebp1 was highly expressed in eyes, brain and intestine. In rabbitfish primary hepatocytes treated with Lxr agonist T0901317, the expression of Lxr and Srebp1 was activated, accompanied by elevated mRNA levels of Δ4 and Δ6/Δ5 fatty acyl desaturase (Fad), key enzymes of LC-PUFA biosynthesis, as well as peroxisome proliferator-activated receptor γ (PPARγ). In addition, Srebp1 displayed higher expression levels in liver of rabbitfish fed a vegetable oil diet or reared at 10 ppt salinity, which were conditions reported to increase the liver expression of Δ4 and Δ6/Δ5 Fad and LC-PUFA biosynthetic ability, than fish fed a fish oil diet or reared at 32 ppt, respectively. These results suggested that Lxr and Srebp1 are involved in regulation of LC-PUFA biosynthesis probably by promoting the expression of two Fad in rabbitfish liver, which, to our knowledge, is the first report in marine teleosts.
A critical assessment of transmethylation procedures for n-3 long-chain polyunsaturated fatty acid quantification of lipid classes.

PubMed

Sehl, Anthony; Couëdelo, Leslie; Fonseca, Laurence; Vaysse, Carole; Cansell, Maud

2018-06-15

Lipid transmethylation methods described in the literature are not always evaluated with care so to insure that the methods are effective, especially on food matrix or biological samples containing polyunsaturated fatty acid (PUFA). The aim of the present study was to select a method suitable for all lipid species rich in long chain n-3 PUFA. Three published methods were adapted and applied on individual lipid classes. Lipid (trans)methylation efficiency was characterized in terms of reaction yield and gas chromatography (GC) analysis. The acid-catalyzed method was unable to convert triglycerides and sterol esters, while the method using an incubation at a moderate temperature was ineffective on phospholipids and sterol esters. On the whole only the method using sodium methoxide and sulfuric acid was effective on lipid classes taken individually or in a complex medium. This study highlighted the use of an appropriate (trans)methylation method for insuring an accurate fatty acid composition. Copyright © 2018 Elsevier Ltd. All rights reserved.
Metabolism, health and fillet nutritional quality in Atlantic salmon (Salmo salar) fed diets containing n-3-rich microalgae.

PubMed

Kousoulaki, Katerina; Østbye, Tone-Kari Knutsdatter; Krasnov, Aleksei; Torgersen, Jacob Seilø; Mørkøre, Turid; Sweetman, John

2015-01-01

Microalgae, as primary producers of EPA and DHA, are among the most prominent alternative sources to fish oil for n-3 long-chain PUFA in animal and human nutrition. The present study aimed to assess technical, nutritional and fish health aspects of producing n-3-rich Atlantic salmon (Salmo salar) fish fillets by dietary supplementation of increasing levels of a DHA-producing Schizochytrium sp. and reduced or without use of supplemental fish oil. Atlantic salmon smolt were fed diets with graded levels of microalgae for 12 weeks, during which all fish showed high feed intake rates with postprandial plasma leptin levels inversely correlating with final mean fish body weights. Fish performance was optimal in all experimental treatments (thermal growth coefficient about 4·0 and feed conversion ratio 0·8-0·9), protein digestibility was equal in all diets, whereas dietary lipid digestibility inversely correlated with the dietary levels of the SFA 16 : 0. Fillet quality was good and similar to the control in all treatments in terms of n-3 long-chain PUFA content, gaping, texture and liquid losses during thawing. Histological fluorescence staining and immunofluorescence analysis of salmon intestines (midgut: base of intestine and villi) revealed significant effects on slime, goblet cell production and inducible nitric oxide synthase (iNOS) activity with increasing levels of dietary Schizochytrium sp. supplementation. Microarray analysis did not reveal any signs of toxicity, stress, inflammation or any other negative effects from Schizochytrium sp. supplementation in diets for Atlantic salmon.
Randomized placebo-controlled pilot trial of omega 3 fatty acids for prevention of aromatase inhibitor-induced musculoskeletal pain.

PubMed

Lustberg, Maryam B; Orchard, Tonya S; Reinbolt, Raquel; Andridge, Rebecca; Pan, Xueliang; Belury, Martha; Cole, Rachel; Logan, Amanda; Layman, Rachel; Ramaswamy, Bhuvaneswari; Wesolowski, Robert; Berger, Michael; Patterson, Elaine; Loprinzi, Charles; Shapiro, Charles L; Yee, Lisa

2018-02-01

Aromatase inhibitor (AI)-induced joint symptoms negatively impact drug adherence and quality of life in breast cancer survivors. Mechanisms underlying symptoms may include inflammation. It is hypothesized that n - 3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and may reduce symptoms. We conducted a randomized, double-blind, placebo-controlled study comparing 4.3 g/day n - 3 PUFA supplements vs placebo for 24 weeks in postmenopausal breast cancer patients starting adjuvant AIs. Primary endpoints were adherence and tolerability; secondary outcomes included inflammatory cytokines and symptoms assessed by the Brief Pain Inventory short form (BPI-SF) and Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) at 0, 12, and 24 weeks. Forty-four women were randomized, of which 35 completed the study. Adherence was ≥ 88% based on these 35 patients with pill counts as well as change in red blood cell (RBC) n - 3 PUFAs. Common toxicities included grade 1 flatulence (55% of both groups) and belching (45% of n - 3 group). Mean pain severity scores (BPI-SF) did not change significantly by time or treatment arm. Quality of life, based on FACT-ES scores, significantly decreased within placebo (p = 0.04), but not the n - 3 group (p = 0.58), with a trend toward between-group differences (p = 0.06) at 12 weeks, but no significant differences at 24 weeks. RBC n - 3 levels were strongly positively correlated with FACT-ES at 12 weeks, but attenuated at 24 weeks. High-dose n - 3 PUFA supplementation is feasible and well tolerated when administered with AIs. Additional studies are needed to evaluate efficacy in prevention of joint symptoms.
Enhanced thermoelectric properties of N-type polycrystalline In4Se3-x compounds via thermally induced Se deficiency

NASA Astrophysics Data System (ADS)

Zhao, Ran; Shu, Yu-Tian; Guo, Fu

2014-03-01

In4Se3-x compound is considered as a potential thermoelectric material due to its comparably low thermal conductivity among all existing ones. While most studies investigated In4Se3-x thermoelectric properties by controlling selennium or other dopants concentrations, in the current study, it was found that even for a fixed initial In/Se ratio, the resulting In/Se ratio varied significantly with different thermal processing histories (i.e., melting and annealing), which also resulted in varied thermoelectric properties as well as fracture surface morphologies of In4Se3-x polycrystalline specimens. Single phase polycrystalline In4Se3-x compounds were synthesized by combining a sequence of melting, annealing, pulverizing, and spark plasma sintering. The extension of previous thermal history was observed to significantly improve the electrical conductivity (about 121%) and figure of merit (about 53%) of In4Se3-x polycrystalline compounds. The extended thermal history resulted in the increase of Se deficiency (x) from 0.39 to 0.53. This thermally induced Se deficiency was observed to associate with increasing carrier mobility but decreasing concentration, which differs from the general trend observed for the initially adjusted Se deficiency at room temperature. Unusually large dispersed grains with nanosize layers were observed in specimens with the longest thermal history. The mechanism(s) by which previous thermal processing enhances carrier mobility and affect microstructural evolution are briefly discussed.
Novel nanoliposomal encapsulated omega-3 fatty acids and their applications in food.

PubMed

Rasti, Babak; Erfanian, Arezoo; Selamat, Jinap

2017-09-01

The aim of the present research was to evaluate the application, stability and suitability of ω3 polyunsaturated fatty acids (PUFAs) incorporated nanoliposomes in food enrichment. Nanoliposomal ω3 PUFAs was prepared by Mozafari method, and their application in bread and milk was compared with unencapsulated (fish oil) and microencapsulated ω3 PUFAs. Sensory evaluation was conducted to determine the perceptible sensory difference/similarity between control, unencapsulated, microencapsulated, and nanoliposomal ω3 PUFAs enriched foods. Results showed no significant (p=0.11) detectable difference between control and nanoliposomal ω3 PUFAs enriched samples while, samples enriched with unencapsulated or microencapsulated ω3 PUFAs showed significant (p=0.02) fishy flavor. Moreover, significantly (p<0.01) higher ω3 PUFAs % recovery and lower peroxide and anisidine values were observed in nanoliposomal ω3 PUFAs enriched samples in comparison with other samples. In conclusion, an effective and reproducible method for application of ω3 PUFAs in the food system was developed. Copyright © 2017 Elsevier Ltd. All rights reserved.
Metabolic and endocrine effects of long-chain versus essential omega-3 polyunsaturated fatty acids in polycystic ovary syndrome.

PubMed

Vargas, M Luisa; Almario, Rogelio U; Buchan, Wendy; Kim, Kyoungmi; Karakas, Sidika E

2011-12-01

The objective of the study was to compare the effects of essential vs long-chain omega (n)-3 polyunsaturated fatty acids (PUFAs) in polycystic ovary syndrome. In this 6-week, prospective, double-blinded, placebo (soybean oil)-controlled study, 51 completers received 3.5 g n-3 PUFA per day (essential PUFA from flaxseed oil or long-chain PUFA from fish oil). Anthropometric variables, cardiovascular risk factors, and androgens were measured; oral glucose tolerance test (OGTT) and frequently sampled intravenous GTT (IVGTT) were conducted at baseline and 6 weeks. Between-group comparisons showed significant differences in serum triglyceride response (P = .0368), whereas the changes in disposition index also tended to differ (P = .0621). When within-group changes (after vs before intervention) were considered, fish oil and flaxseed oil lowered serum triglyceride (P = .0154 and P = .0176, respectively). Fish oil increased glucose at 120 minutes of OGTT (P = .0355), decreased the Matsuda index (P = .0378), and tended to decrease acute insulin response during IVGTT (P = .0871). Soybean oil increased glucose at 30 (P = .0030) and 60 minutes (P = .0121) and AUC for glucose (P = .0122) during OGTT, tended to decrease acute insulin response during IVGTT (P = .0848), reduced testosterone (P = .0216), and tended to reduce sex hormone-binding globulin (P = .0858). Fasting glucose, insulin, adiponectin, leptin, or high-sensitivity C-reactive protein did not change with any intervention. Long-chain vs essential n-3 PUFA-rich oils have distinct metabolic and endocrine effects in polycystic ovary syndrome; and therefore, they should not be used interchangeably. Published by Elsevier Inc.
Fish Oil and Post-Operative Atrial Fibrillation – Results of the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Trial

PubMed Central

Mozaffarian, Dariush; Marchioli, Roberto; Macchia, Alejandro; Silletta, Maria G.; Ferrazzi, Paolo; Gardner, Timothy J.; Latini, Roberto; Libby, Peter; Lombardi, Federico; O’Gara, Patrick T.; Page, Richard L.; Tavazzi, Luigi; Tognoni, Gianni

2013-01-01

Context Post-operative atrial fibrillation/flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and healthcare utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFA) reduce post-op AF, with mixed results. Objective To determine whether peri-operative n-3-PUFA supplementation reduces post-op AF. Design Randomized, double-blind, placebo-controlled, multinational, clinical trial. Patients A total of 1,516 patients scheduled for cardiac surgery across 28 centers in the US, Italy, and Argentina, enrolled between Aug 2010 and Jun 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. Forty-eight percent of screened patients and 94% of eligible patients were enrolled. Intervention Patients were randomized to receive fish oil (1 g capsules containing ≥840 mg n-3-PUFA as ethyl esters) or placebo, with pre-operative loading of 10g over 3-5 days (or 8g over 2 days) followed post-operatively by 2g/d until hospital discharge or post-op day10, whichever first. Main Outcome Measures The primary endpoint was occurrence of post-op AF >30 sec. We also evaluated post-op AF lasting >1hr, resulting in symptoms, or treated with cardioversion; other secondary post-op AF endpoints; other tachyarrhythmias; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events. All endpoints and analyses plans were prespecified. Results At enrollment, mean±SD age was 64±13 years, 72.2% were male, and 51.8% had planned valvular surgery. The primary endpoint occurred in 233 (30.7%) and 227 (30.0%) patients assigned to placebo and n-3-PUFA, respectively (OR=0.96, 95%CI=0.77-1.20; P=0.74). None of the secondary endpoints were significantly different, including post-op AF that was sustained, symptomatic, or treated (n=231 [30.5%] vs. n=224 [29.6%], P=0.70) or number of
Omega-3 Supplementation Lowers Inflammation and Anxiety in Medical Students: A Randomized Controlled Trial

PubMed Central

Kiecolt-Glaser, Janice K.; Belury, Martha A.; Andridge, Rebecca; Malarkey, William B.; Glaser, Ronald

2011-01-01

Observational studies have linked lower omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and higher omega-6 (n-6) PUFAs with inflammation and depression, but randomized controlled trial (RCT) data have been mixed. To determine whether n-3 decreases proinflammatory cytokine production and depressive and anxiety symptoms in healthy young adults, this parallel group, placebo-controlled, double-blind 12-week RCT compared n-3 supplementation with placebo. The participants, 68 medical students, provided serial blood samples during lower-stress periods as well as on days before an exam. The students received either n-3 (2.5 g/d, 2085 mg eicosapentaenoic acid and 348 mg docosahexanoic acid) or placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Compared to controls, those students who received n-3 showed a 14% decrease in lipopolysaccharide (LPS) stimulated interleukin 6 (IL-6) production and a 20% reduction in anxiety symptoms, without significant change in depressive symptoms. Individuals differ in absorption and metabolism of n-3 PUFA supplements, as well as in adherence; accordingly, planned secondary analyses that used the plasma n-6:n-3 ratio in place of treatment group showed that decreasing n-6:n-3 ratios led to lower anxiety and reductions in stimulated IL-6 and tumor necrosis factor alpha (TNF-α) production, as well as marginal differences in serum TNF-α. These data suggest that n-3 supplementation can reduce inflammation and anxiety even among healthy young adults. The reduction in anxiety symptoms associated with n-3 supplementation provides the first evidence that n-3 may have potential anxiolytic benefits for individuals without an anxiety disorder diagnosis. ClinicalTrials.gov identifier: NCT00519779 PMID:21784145
Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kusunoki, Chisato, E-mail: yosizaki@belle.shiga-med.ac.jp; Yang, Liu; Yoshizaki, Takeshi

Highlights: Black-Right-Pointing-Pointer Omega-3 PUFA has a direct anti-oxidant effect in adipocytes. Black-Right-Pointing-Pointer EPA and DHA induce HO-1 expression in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer Omega-3 PUFA and its end-product, 4-HHE, activates the Nrf-2/HO-1 pathway. Black-Right-Pointing-Pointer Omega-3 PUFA protects against oxidative stress-induced cytotoxicity. -- Abstract: Oxidative stress is produced in adipose tissue of obese subjects and has been associated with obesity-related disorders. Recent studies have shown that omega-3 polyunsaturated fatty acid ({omega}3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of {omega}3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treatedmore » with {omega}3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). {omega}3-PUFA and its metabolites dose-dependently increased mRNA and protein levels of the anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well-known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor 2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein expression. Also, pretreatment with {omega}3-PUFA prevented H{sub 2}O{sub 2}-induced cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value for clinical conditions associated with systemic oxidative stress.« less
Spectra of normal and nutrient-deficient maize leaves

NASA Technical Reports Server (NTRS)

Al-Abbas, A. H.; Barr, R.; Hall, J. D.; Crane, F. L.; Baumgardner, M. F.

1973-01-01

Reflectance, transmittance and absorptance spectra of normal and six types of nutrient-deficient (N, P, K, S, Mg, and Ca) maize (Zea mays L.) leaves were analyzed at 30 selected wavelengths from 500 to 2600 nm. The analysis of variance showed significant differences in reflectance, transmittance and absorptance in the visible wavelengths among leaf numbers 3, 4, and 5, among the seven treatments, and among the interactions of leaf number and treatments. In the infrared wavelengths only treatments produced significant differences. The chlorophyll content of leaves was reduced in all nutrient-deficient treatments. Percent moisture was increased in S-, Mg-, and N-deficiencies. Polynomial regression analysis of leaf thickness and leaf moisture content showed that these two variables were significantly and directly related. Leaves from the P- and Ca-deficient plants absorbed less energy in the near infrared than the normal plants; S-, Mg-, K-, and N-deficient leaves absorbed more than the normal. Both S- and N-deficient leaves had higher temperatues than normal maize leaves.
Omega-3 Fatty Acid Supplementation Improves Endothelial Function in Primary Antiphospholipid Syndrome: A Small-Scale Randomized Double-Blind Placebo-Controlled Trial.

PubMed

Felau, Sheylla M; Sales, Lucas P; Solis, Marina Y; Hayashi, Ana Paula; Roschel, Hamilton; Sá-Pinto, Ana Lúcia; Andrade, Danieli Castro Oliveira De; Katayama, Keyla Y; Irigoyen, Maria Claudia; Consolim-Colombo, Fernanda; Bonfa, Eloisa; Gualano, Bruno; Benatti, Fabiana B

2018-01-01

Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n = 11) or n-3 PUFA (ω-3, n = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%, p = 0.06, ES = 0.9; and +23 vs. -22%, p = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels ( p > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%, p = 0.04, ES = -0.9) and tumor necrosis factor (-13 vs. +0.3%, p = 0.04, ES = -0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p = 0.1, ES = -0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an
N-Methylpyrrolidone Hydroperoxide/Cs2 CO3 as an Excellent Reagent System for the Hydroxy-Directed Diastereoselective Epoxidation of Electron-Deficient Olefins.

PubMed

Victor, Napoleon John; Gana, Janardhanan; Muraleedharan, Kannoth Manheri

2015-10-12

This report introduces N-methylpyrrolidone hydroperoxide (NMPOOH)/base as an excellent reagent system for hydroxy-directed syn selective epoxidation of electron-deficient olefins, characterized by high diastereoselectivity, short reaction times and remarkable chemoselectivity, especially in presence of oxidatively labile nitrogen or sulfur atoms. NMPOOH also proves efficient in the oxidation of electron-deficient aromatic aldehydes, in the removal of oxazolidinone chiral auxiliary, and in the functionalization of alkenes and alkynes, showing wide application potential. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
ANALYSIS OF ω-3 FATTY ACID CONTENT OF POLISH FISH OIL DRUG AND DIETARY SUPPLEMENTS.

PubMed

Osadnik, Kamila; Jaworska, Joanna

2016-07-01

Study results indicate that a diet rich in polyunsaturated fatty acids ω-3 (PUFA n-3) exerts favorable effect on human health, accounting for reduced cardiovascular morbidity and mortality. PUFA n-3 contained in marine fish oils, particularly eicosapentaenoic (EPA, 20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) acids, are attributed antithrombotic, anti-inflammatory, anti-atherosclerotic and anti-arrhythmic effects. They have also beneficial effects on cognitive functions and immunological mechanisms of an organism. Considering the fact that marine fish are not abundant in Western diet, the pharmaceutical industry reacts with a broad selection of PUFA n-3 containing dietary supplements and drugs. Increased consumers' interest with those products has been observed recently. Therefore, their quality, understood as reliability of manufacturer's declaration of composition of offered dietary supplements, is highly important. We have tested 22 products available in pharmacies and supermarkets, manufacturers of which declared content of n-3 fatty acids (21 dietary supplements and I drug). Identity and content of DHA and EPA were assessed using ¹H NMR spectroscopy, based on characteristic signals from protons in methylene groups. Almost one in five of the examined dietary supplements contains < 89% of the PUFA n-3 amount declared by its manufacturer. For a majority of tested products the manufacturer-declared information regarding DHA (58%) and EPA (74%) content was consistent with the actual composition. It is notable that more cases of discrepancy between the declared and the actual content regarded DHA than EPA, which indicates a less favorable balance, considering the pro-health effect of those acids. Over a half of tested products provides the supplementary dose (250 mg/day) with one capsule taken daily, and in 27% of cases the daily dosage should be doubled. Only 10% of those products ensure the appropriate dose for cardiovascular patients (1 g/day) with the use of

The induction of apoptosis in pre-malignant keratinocytes by omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is inhibited by albumin.

PubMed

Nikolakopoulou, Zacharoula; Shaikh, Mushfiq Hassan; Dehlawi, Hebah; Michael-Titus, Adina Teodora; Parkinson, Eric Kenneth

2013-04-12

The long chain omega-3 polyunsaturated fatty acids (PUFA) have been reported to exert anti-cancer effects. At this study we tested the effect of the omega-3 PUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on pre-malignant keratinocytes growth in the well-characterised human pre-malignant epidermal cell line, HaCaT and attempted to identify a PUFA serum antagonist. Both EPA and DHA inhibited HaCaT growth and induced apoptosis. At the 10% (v/v) foetal bovine serum (FBS) medium, limited growth inhibition (3-20% for 50μM DHA and EPA respectively) and negligible apoptosis were observed with PUFA use. However, at 3% (v/v) FBS medium, 30-50μM of PUFA caused impressive levels of growth inhibition (82-83% for 50μM DHA and EPA respectively) and increase of apoptosis (8-19% increase in 72h). None of the numerous serum growth factors present in FBS or the antioxidant n-tert-butyl-α-phenylnitrone could inhibit the PUFA-induced cytotoxicity. In contrast, bovine and human albumin (0.1-0.3%, w/v) significantly antagonized the growth inhibitory and apoptosis-inducing effects of PUFA. In conclusion, we have shown for the first time that omega-3 PUFA inhibit the growth and induce apoptosis of pre-malignant keratinocytes and identified albumin as a major antagonistic factor in serum that could limit their effectiveness at pharmacologically-achievable doses. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Effect of seafood mediated PCB exposure on desaturase activity and PUFA profile in Faroese septuagenarians.

PubMed

Tøttenborg, Sandra Søgaard; Choi, Anna L; Bjerve, Kristian S; Weihe, Pal; Grandjean, Philippe

2015-07-01

Polychlorinated biphenyl (PCB) exposure may affect serum concentrations of polyunsaturated fatty acids (PUFAs) by inhibiting desaturases ∆5 and ∆6 that drive their synthesis from precursor fatty acids. Such changes in the composition of fatty acids may affect cardiovascular disease risk, which is thought to increase at elevated PCB exposures. This population-based cross-sectional study examined 712 Faroese men and women aged 70-74 years. The serum phospholipid fraction of fasting blood samples was used to determine the PUFA profile, including linoleic acid, dihomo-γ-linolenic acid, arachidonic acid, eicosatrienoic acid, and other relevant fatty acids. Ratios between precursor and metabolite fatty acids were used as proxies for ∆5 and ∆6 desaturase activity. Tertiles of serum-PCB concentrations were used in multiple regression analyses to determine the association between the exposure and desaturase activity. In multiple regression models, PCB exposure was inversely related to the estimated Δ6 desaturase activity resulting in accumulation of precursor fatty acids and decrease in the corresponding product PUFAs. A positive association between PCB and Δ5 desaturation was also found. A relative increase in EA was also observed, though only in the third tertile of PCB exposure. Non-linear relationships between the exposure and the desaturase activity were not found. Consuming fish and seafood may not be translated into beneficial fatty acid profiles if the diet simultaneously causes exposure to PCBs. Although the desaturase estimates were likely influenced by dietary intakes of product PUFAs, the association between PCB exposure and ∆6 desaturase activity is plausible and may affect cardiovascular disease risk. Copyright © 2015 Elsevier Inc. All rights reserved.
Lipid characteristics of a seep clam, Mesolinga soliditesta: Comparison with those of two coastal clams, Meretrix lamarckii and Ruditapes philippinarum

NASA Astrophysics Data System (ADS)

Saito, Hiroaki; Murata, Masakazu; Hashimoto, Jun

2014-12-01

The lipids and fatty acids of two coastal clams, Meretrix lamarckii and Ruditapes philippinarum, collected at 5 and 1 m of depth, and a seep clam, Mesolinga soliditesta, collected at 331 m of depth, were examined to assess their lipid physiology and trophic relationship with their diets. The major fatty acids of lipids in Mer. lamarckii and R. philippinarum were 14:0, 16:0, 18:0, 16:1n-7, 18:1n-9, 18:1n-7, 20:4n-6, 20:5n-3, and 22:6n-3, while those of Mes. soliditesta were 16:0, 18:0, 16:1n-7, 18:1n-7, 20:1n-7, 20:1n-13, 20:2n-7, 15 (Δ5,13-20:2), and 22:2n-7,15 (Δ7,15-22:2). The major polyunsaturated fatty acids (PUFAs) in the Mer. lamarckii and R. philippinarum lipids consisted of various n-3 and n-6 long-chain (LC) PUFAs, such as 20:4n-6, 22:4n-6, 20:5n-3, 22:5n-3, and 22:6n-3, while those in Mes. soliditesta muscle and viscera included various n-4 family PUFAs (18:3n-7, 18:4n-4, 20:2n-7, and 20:3n-7) with limited kinds of n-3 and n-6 PUFAs (20:4n-6 and 20:5n-3). These findings indicate that, like other common shallow-water clams, Mer. lamarckii and R. philippinarum ingest phytoplanktonic n-3 and n-6 LC-PUFAs, whereas Mes. soliditesta utilizes limited kinds of n-3 and n-6 LC-PUFAs. In contrast to the other two bivalves species, Mes. soliditesta yielded various n-4 and n-7 (n-4/n-7) PUFAs, which were assimilated from the chemosynthetic symbionts. The high diversity of PUFAs contained in the Mes. soliditesta lipids (n-3, n-4 family, and n-6 PUFAs) suggests that this species mixotrophically utilized both photosynthetic products and vent chemosynthetic nutrition derived from geothermal energy.
Replacement of Marine Fish Oil with de novo Omega-3 Oils from Transgenic Camelina sativa in Feeds for Gilthead Sea Bream (Sparus aurata L.).

PubMed

Betancor, Mónica B; Sprague, M; Montero, D; Usher, S; Sayanova, O; Campbell, P J; Napier, J A; Caballero, M J; Izquierdo, M; Tocher, D R

2016-10-01

Omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA) are essential components of the diet of all vertebrates. The major dietary source of n-3 LC-PUFA for humans has been fish and seafood but, paradoxically, farmed fish are also reliant on marine fisheries for fish meal and fish oil (FO), traditionally major ingredients of aquafeeds. Currently, the only sustainable alternatives to FO are vegetable oils, which are rich in C18 PUFA, but devoid of the eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) abundant in FO. Two new n-3 LC-PUFA sources obtained from genetically modified (GM) Camelina sativa containing either EPA alone (ECO) or EPA and DHA (DCO) were compared to FO and wild-type camelina oil (WCO) in juvenile sea bream. Neither ECO nor DCO had any detrimental effects on fish performance, although final weight of ECO-fed fish (117 g) was slightly lower than that of FO- and DCO-fed fish (130 and 127 g, respectively). Inclusion of the GM-derived oils enhanced the n-3 LC-PUFA content in fish tissues compared to WCO, although limited biosynthesis was observed indicating accumulation of dietary fatty acids. The expression of genes involved in several lipid metabolic processes, as well as fish health and immune response, in both liver and anterior intestine were altered in fish fed the GM-derived oils. This showed a similar pattern to that observed in WCO-fed fish reflecting the hybrid fatty acid profile of the new oils. Overall the data indicated that the GM-derived oils could be suitable alternatives to dietary FO in sea bream.
Alpha Lipoic Acid Plus Omega-3 Fatty Acids for Vestibulodynia Associated With Painful Bladder Syndrome.

PubMed

Murina, Filippo; Graziottin, Alessandra; Felice, Raffaele; Gambini, Dania

2017-03-01

This study assessed the effectiveness of alpha lipoic acid (ALA) plus omega-3 polyunsaturated fatty acids (n-3 PUFAs) in combination with amitriptyline therapy in patients with vestibulodynia/painful bladder syndrome (VBD/PBS). Women with VBD/PBS were randomly assigned to receive amitriptyline or amitriptyline plus a commercially available preparation (ALAnerv Age; Alfa Wassermann, Bologna, Italy) containing, in 2 capsules, ALA 600 mg plus docosahexaenoic acid 250 mg and eicosapentaenoic acid 16.67 mg. Symptoms of burning and pain were assessed using a 10-cm visual analog scale and the short form of the McGill-Melzack Pain Questionnaire. Among 84 women who were randomized, the mean ± standard deviation dose of amitriptyline was 21.7 ± 6.6 mg/day, without statistical difference between the two groups. Pain, as assessed using both the pain rating index of the visual analog scale and the short-form McGill Pain Questionnaire, decreased significantly in both trial groups, with a greater effect seen with the addition of ALA and n-3 PUFAs. The addition of ALA/n-3 PUFAs to amitriptyline treatment was also associated with improvements in dyspareunia and pelvic floor muscle tone. The overall incidence of adverse events was low, and none led to treatment discontinuation. The addition of ALA/n-3 PUFAs to amitriptyline treatment in patients with VBD/PBS appears to improve outcomes and may allow for a lower dosage of amitriptyline, which may lead to fewer adverse effects. Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.
Effect of omega-3 and omega-6 polyunsaturated fatty acid enriched diet on plasma IGF-1 and testosterone concentration, puberty and semen quality in male buffalo.

PubMed

Tran, L V; Malla, B A; Sharma, A N; Kumar, Sachin; Tyagi, Nitin; Tyagi, A K

2016-10-01

The objective of the present study was to evaluate the effect of omega-3 and omega-6 PUFA enriched diet on plasma IGF-1 and testosterone concentrations, puberty, sperm fatty acid profile and semen quality in male buffalo. Eighteen male buffalo calves were distributed randomly in three different groups and fed concentrate mixture along with green fodder and wheat straw in 50:40:10 ratios as per requirements. Basis ration of animals in group I was supplemented with 4% of prilled fat (PFA), while in group II and group III were added 4.67% of Calcium salt from Soybean (CaSFA) and Linseed oil (CaLFA), respectively. Male buffalo fed omega-3 PUFA high diet significantly increased concentrations of IGF-1 and testosterone in plasma as compared to two other diets (p<0.05). The age of puberty and scrotal circumference significantly increased by dietary fat effect (p<0.05) of which n-3 PUFA enriched diet (CaLFA) had the largest influence as compared to other diets (PFA and CaSFA). Feeding of n-3 PUFA rich diet significantly increased the DHA (C22:6n-3) content in sperm (p<0.05), which contributed to increased fluidity of plasma membrane, elevated quality of sperm (motility, viability) and in vitro fertility (plasma membrane integrity, acrosome integrity) in both fresh and post-thawing semen. These findings indicate that feeding of n-3 PUFA enriched diet increased IGF-1 and testosterone secretion, reduced pubertal age and improved both fresh and post-thawing semen quality in male buffalo. Copyright © 2016 Elsevier B.V. All rights reserved.
Neuroprotective Properties of the Marine Carotenoid Astaxanthin and Omega-3 Fatty Acids, and Perspectives for the Natural Combination of Both in Krill Oil

PubMed Central

Barros, Marcelo P.; Poppe, Sandra C.; Bondan, Eduardo F.

2014-01-01

The consumption of marine fishes and general seafood has long been recommended by several medical authorities as a long-term nutritional intervention to preserve mental health, hinder neurodegenerative processes, and sustain cognitive capacities in humans. Most of the neurological benefits provided by frequent seafood consumption comes from adequate uptake of omega-3 and omega-6 polyunsaturated fatty acids, n-3/n-6 PUFAs, and antioxidants. Optimal n-3/n-6 PUFAs ratios allow efficient inflammatory responses that prevent the initiation and progression of many neurological disorders. Moreover, interesting in vivo and clinical studies with the marine antioxidant carotenoid astaxanthin (present in salmon, shrimp, and lobster) have shown promising results against free radical-promoted neurodegenerative processes and cognition loss. This review presents the state-of-the-art applications of n-3/n-6 PUFAs and astaxanthin as nutraceuticals against neurodegenerative diseases associated with exacerbated oxidative stress in CNS. The fundamental “neurohormesis” principle is discussed throughout this paper. Finally, new perspectives for the application of a natural combination of the aforementioned anti-inflammatory and antioxidant agents (found in krill oil) are also presented herewith. PMID:24667135
Omega-3 polyunsaturated fatty acids provided during embryonic development improve the growth performance and welfare of Muscovy ducks (Cairina moschata).

PubMed

Baéza, E; Chartrin, P; Bordeau, T; Lessire, M; Thoby, J M; Gigaud, V; Blanchet, M; Alinier, A; Leterrier, C

2017-09-01

The welfare of ducks can be affected by unwanted behaviors such as excessive reactivity and feather pecking. Providing long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) during gestation and early life has been shown to improve the brain development and function of human and rodent offspring. The aim of this study was to test whether the pecking behavior of Muscovy ducks during rearing could be reduced by providing LC n-3 PUFA during embryonic and/or post-hatching development of ducklings. Enrichment of eggs, and consequently embryos, with LC n-3 PUFA was achieved by feeding female ducks (n-3F) a diet containing docosahexaenoic (DHA) and linolenic acids (microalgae and linseed oil). A control group of female ducks (CF) was fed a diet containing linoleic acid (soybean oil). Offspring from both groups were fed starter and grower diets enriched with DHA and linolenic acid or only linoleic acid, resulting in four treatment groups with 48 ducklings in each. Several behavioral tests were performed between 1 and 3 weeks of age to analyze the adaptation ability of ducklings. The growth performance, time budget, social interactions, feather growth, and pecking behavior of ducklings were recorded regularly during the rearing period. No significant interaction between maternal and duckling feeding was found. Ducklings from n-3F ducks had a higher body weight at day 0, 28, and 56, a lower feed conversion ratio during the growth period, and lower reactivity to stress than ducklings from CF ducks. Ducklings from n-3F ducks also exhibited a significantly reduced feather pecking frequency at 49 and 56 days of age and for the whole rearing period. Moreover, consumption of diets enriched with n-3 PUFA during the starter and grower post-hatching periods significantly improved the tibia mineralization of ducklings and the fatty acid composition of thigh muscles at 84 days of age by increasing the n-3 FA content. © 2017 Poultry Science Association Inc.
Interplay Between n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids and the Endocannabinoid System in Brain Protection and Repair.

PubMed

Dyall, Simon C

2017-11-01

The brain is enriched in arachidonic acid (ARA) and docosahexaenoic acid (DHA), long-chain polyunsaturated fatty acids (LCPUFAs) of the n-6 and n-3 series, respectively. Both are essential for optimal brain development and function. Dietary enrichment with DHA and other long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA), has shown beneficial effects on learning and memory, neuroinflammatory processes, and synaptic plasticity and neurogenesis. ARA, DHA and EPA are precursors to a diverse repertoire of bioactive lipid mediators, including endocannabinoids. The endocannabinoid system comprises cannabinoid receptors, their endogenous ligands, the endocannabinoids, and their biosynthetic and degradation enzymes. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the most widely studied endocannabinoids and are both derived from phospholipid-bound ARA. The endocannabinoid system also has well-established roles in neuroinflammation, synaptic plasticity and neurogenesis, suggesting an overlap in the neuroprotective effects observed with these different classes of lipids. Indeed, growing evidence suggests a complex interplay between n-3 and n-6 LCPUFA and the endocannabinoid system. For example, long-term DHA and EPA supplementation reduces AEA and 2-AG levels, with reciprocal increases in levels of the analogous endocannabinoid-like DHA and EPA-derived molecules. This review summarises current evidence of this interplay and discusses the therapeutic potential for brain protection and repair.
Polyunsaturated fatty acids and inflammatory markers in major depressive episodes during pregnancy.

PubMed

Chang, Jane Pei-Chen; Lin, Chih-Ying; Lin, Pan-Yen; Shih, Yin-Hua; Chiu, Tsan-Hung; Ho, Ming; Yang, Hui-Ting; Huang, Shih-Yi; Gałecki, Piotr; Su, Kuan-Pin

2018-01-03

Prenatal depression (PND) is a common psychiatric disorder in pregnant women and leads to psychosocial dysfunction, high suicidal rate, and adverse childcare. Patients with PND have omega-3 polyunsaturated fatty acid (omega-3 or n-3 PUFAs) deficits, which might link to chronic low-grade inflammatory process and the pathophysiological mechanisms of depression. In this case-control study, we examined the levels of PUFAs and inflammatory cytokines in PND. Blood samples were obtained and analyzed from 16 healthy controls and 17 depressed cases (PND group) diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Independent sample t-test and correlation analysis were performed with Statistical Package for the Social Sciences (SPSS) logistics correlation analysis. PND group had significantly lower levels of total n-3 (p=0.026), docosahexaenoic acid (DHA) (p=0.020) and eicosapentaenoic (EPA) (p=0.019) but a higher omega-6 (n-6)/n-3 PUFAs ratio (p=0.007) and tumor necrosis factor alpha (TNF-α) (p=0.016) level. Moreover, the duration of current PND episodes were also significantly correlated with DHA, EPA, n-3 PUFAs, n-6/n-3 ratio and TNF-α. In terms of PUFAs and cytokine levels, only DHA was inversely correlated with TNF-α. PND is significantly associated with lower DHA, EPA, and total n-3 PUFAs levels and an increased n-6/n-3 PUFAs ratio, while the duration of PND is associated with lower levels of n-3 PUFAs, including DHA and EPA. The correlation of PUFAs levels with depression and TNF-α level grant further investigation into the inflammatory process underlying PND, mediated by PUFAs. Copyright © 2017 Elsevier Inc. All rights reserved.
Genetics Home Reference: GM3 synthase deficiency

MedlinePlus

... GM3 synthase deficiency is characterized by recurrent seizures (epilepsy) and problems with brain development. Within the first ... Testing (1 link) Genetic Testing Registry: Amish infantile epilepsy syndrome Other Diagnosis and Management Resources (2 links) ...
Simple method to distinguish between primary and secondary C3 deficiencies.

PubMed

Pereira de Carvalho Florido, Marlene; Ferreira de Paula, Patrícia; Isaac, Lourdes

2003-03-01

Due to the increasing numbers of reported clinical cases of complement deficiency in medical centers, clinicians are now more aware of the role of the complement system in the protection against infections caused by microorganisms. Therefore, clinical laboratories are now prepared to perform a number of diagnostic tests of the complement system other than the standard 50% hemolytic component assay. Deficiencies of alternative complement pathway proteins are related to severe and recurrent infections; and the application of easy, reliable, and low-cost methods for their detection and distinction are always welcome, notably in developing countries. When activation of the alternative complement pathway is evaluated in hemolytic agarose plates, some but not all human sera cross-react to form a late linear lysis. Since the formation of this linear lysis is dependent on C3 and factor B, it is possible to use late linear lysis to routinely screen for the presence of deficiencies of alternative human complement pathway proteins such as factor B. Furthermore, since linear lysis is observed between normal human serum and primary C3-deficient serum but not between normal human serum and secondary C3-deficient serum caused by the lack of factor H or factor I, this assay may also be used to discriminate between primary and secondary C3 deficiencies.
Maternal plasma polyunsaturated fatty acid levels during pregnancy and childhood lipids and insulin levels

PubMed Central

Vidakovic, Aleksandra Jelena; Jaddoe, Vincent WV; Voortman, Trudy; Demmelmair, Hans; Koletzko, Berthold; Gaillard, Romy

2017-01-01

Background and Aims Maternal polyunsaturated fatty acid (PUFA) levels are associated with cord blood lipid and insulin levels. Not much is known about the influence of maternal PUFAs during pregnancy on long-term offspring lipid and insulin metabolism. We examined the associations of maternal plasma n-3 and n-6 PUFA levels during pregnancy with childhood lipids and insulin levels. Methods and Results In a population-based prospective cohort study among 3,230 mothers and their children, we measured maternal second trimester n-3 and n-6 PUFA plasma levels. At the median age of 6.0 years (95% range, 5.6-7.9), we measured childhood total-cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, insulin and c-peptide levels. Higher maternal total n-3 PUFA levels, and specifically DHA levels, were associated with higher childhood total-cholesterol, HDL-cholesterol and insulin levels (p-values <0.05), but not with LDL-cholesterol and triglycerides. Maternal total n-6 PUFA levels were not associated with childhood outcomes, but higher levels of the individual n-6 PUFAs, EDA and DGLA were associated with a lower childhood HDL-cholesterol, and higher AA levels with higher childhood total-cholesterol and HDL-cholesterol levels (all p-values <0.05). A higher maternal n-6/n-3 PUFA ratio was only associated with lower childhood HDL-cholesterol and insulin levels (p-values <0.05). These associations were not explained by childhood body mass index. Conclusions Higher maternal total n-3 PUFAs and specifically DHA levels during pregnancy are associated with higher childhood total-cholesterol, HDL-cholesterol and insulin levels. Only individual maternal n-6 PUFAs, not total maternal n-6 PUFA levels, tended to be associated with childhood lipids and insulin levels. PMID:27919543
Neuroprotective Effects of Omega-3 Polyunsaturated Fatty Acids in a Rat Model of Anterior Ischemic Optic Neuropathy.

PubMed

Georgiou, Tassos; Wen, Yao-Tseng; Chang, Chung-Hsing; Kolovos, Panagiotis; Kalogerou, Maria; Prokopiou, Ekatherine; Neokleous, Anastasia; Huang, Chin-Te; Tsai, Rong-Kung

2017-03-01

The purpose of this study was to investigate the therapeutic effect of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration in a rat model of anterior ischemic optic neuropathy (rAION). The level of blood arachidonic acid/eicosapentaenoic acid (AA/EPA) was measured to determine the suggested dosage. The rAION-induced rats were administered fish oil (1 g/day EPA) or phosphate-buffered saline (PBS) by daily gavage for 10 consecutive days to evaluate the neuroprotective effects. Blood fatty acid analysis showed that the AA/EPA ratio was reduced from 17.6 to ≤1.5 after 10 days of fish oil treatment. The retinal ganglion cell (RGC) densities and the P1-N2 amplitude of flash visual-evoked potentials (FVEP) were significantly higher in the ω-3 PUFA-treated group, compared with the PBS-treated group (P < 0.05). The number of apoptotic cells in the RGC layer of the ω-3 PUFA-treated rats was significantly decreased (P < 0.05) compared with that of the PBS-treated rats. Treatment with ω-3 PUFAs reduced the macrophage recruitment at the optic nerve (ON) by 3.17-fold in the rAION model. The M2 macrophage markers, which decrease inflammation, were induced in the ω-3 PUFA-treated group in contrast to the PBS-treated group. In addition, the mRNA levels of tumor necrosis factor-alpha, interleukin-1 beta, and inducible nitric oxide synthase were significantly reduced in the ω-3 PUFA-treated group. The administration of ω-3 PUFAs has neuroprotective effects in rAION, possibly through dual actions of the antiapoptosis of RGCs and anti-inflammation via decreasing inflammatory cell infiltration, as well as the regulation of macrophage polarization to decrease the cytokine-induced injury of the ON.
Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age.

PubMed

Boucher, Olivier; Burden, Matthew J; Muckle, Gina; Saint-Amour, Dave; Ayotte, Pierre; Dewailly, Eric; Nelson, Charles A; Jacobson, Sandra W; Jacobson, Joseph L

2011-05-01

The beneficial effects of prenatal and early postnatal intakes of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on cognitive development during infancy are well recognized. However, few studies have examined the extent to which these benefits continue to be evident in childhood. The aim of this study was to examine the relation of n-3 PUFAs and seafood-contaminant intake with memory function in school-age children from a fish-eating community. In a prospective, longitudinal study in Arctic Quebec, we assessed Inuit children (n = 154; mean age: 11.3 y) by using a continuous visual recognition task to measure 2 event-related potential components related to recognition memory processing: the FN400 and the late positive component (LPC). Children were also examined by using 2 well-established neurobehavioral assessments of memory: the Digit span forward from Wechsler Intelligence Scales for Children, 4th edition, and the California Verbal Learning Test-Children's Version. Repeated-measures analyses of variance revealed that children with higher cord plasma concentrations of docosahexaenoic acid (DHA), which is an important n-3 PUFA, had a shorter FN400 latency and a larger LPC amplitude; and higher plasma DHA concentrations at the time of testing were associated with increased FN400 amplitude. Cord DHA-related effects were observed regardless of seafood-contaminant amounts. Multiple regression analyses also showed positive associations between cord DHA concentrations and performance on neurobehavioral assessments of memory. To our knowledge, this study provides the first neurophysiologic and neurobehavioral evidence of long-term beneficial effects of n-3 PUFA intake in utero on memory function in school-age children.
Nutritional skewing of conceptus sex in sheep: effects of a maternal diet enriched in rumen-protected polyunsaturated fatty acids (PUFA).

PubMed

Green, Mark P; Spate, Lee D; Parks, Tina E; Kimura, Koji; Murphy, Clifton N; Williams, Jim E; Kerley, Monty S; Green, Jonathan A; Keisler, Duane H; Roberts, R Michael

2008-06-09

Evolutionary theory suggests that in polygynous mammalian species females in better body condition should produce more sons than daughters. Few controlled studies have however tested this hypothesis and controversy exists as to whether body condition score or maternal diet is in fact the determining factor of offspring sex. Here, we examined whether maternal diet, specifically increased n-6 polyunsaturated fatty acid (PUFA) intake, of ewes with a constant body condition score around the time of conception influenced sex ratio. Ewes (n = 44) maintained in similar body condition throughout the study were assigned either a control (C) diet or one (F) enriched in rumen-protected PUFA, but otherwise essentially equivalent, from four weeks prior to breeding until d13 post-estrus. On d13, conceptuses were recovered, measured, cultured to assess their capacity for interferon-tau (IFNT) production and their sex determined. The experiment was repeated with all ewes being fed the F diet to remove any effects of parity order on sex ratio. Maternal body condition score (BCS), plasma hormone and metabolite concentrations were also assessed throughout the study and related to diet. In total 129 conceptuses were recovered. Ewes on the F diet produced significantly more male than female conceptuses (proportion male = 0.69; deviation from expected ratio of 0.5, P < 0.001). Conceptus IFNT production was unaffected by diet (P > 0.1), but positively correlated with maternal body condition score (P < 0.05), and was higher (P < 0.05) in female than male conceptuses after 4 h culture. Maternal plasma hormone and metabolite concentrations, especially progesterone and fatty acid, were also modulated by diet. These results provide evidence that maternal diet, in the form of increased amounts of rumen-protected PUFA fed around conception, rather than maternal body condition, can skew the sex ratio towards males. These observations may have implications to the livestock industry and animal
Nutritional skewing of conceptus sex in sheep: effects of a maternal diet enriched in rumen-protected polyunsaturated fatty acids (PUFA)

PubMed Central

Green, Mark P; Spate, Lee D; Parks, Tina E; Kimura, Koji; Murphy, Clifton N; Williams, Jim E; Kerley, Monty S; Green, Jonathan A; Keisler, Duane H; Roberts, R Michael

2008-01-01

Background Evolutionary theory suggests that in polygynous mammalian species females in better body condition should produce more sons than daughters. Few controlled studies have however tested this hypothesis and controversy exists as to whether body condition score or maternal diet is in fact the determining factor of offspring sex. Here, we examined whether maternal diet, specifically increased n-6 polyunsaturated fatty acid (PUFA) intake, of ewes with a constant body condition score around the time of conception influenced sex ratio. Methods Ewes (n = 44) maintained in similar body condition throughout the study were assigned either a control (C) diet or one (F) enriched in rumen-protected PUFA, but otherwise essentially equivalent, from four weeks prior to breeding until d13 post-estrus. On d13, conceptuses were recovered, measured, cultured to assess their capacity for interferon-tau (IFNT) production and their sex determined. The experiment was repeated with all ewes being fed the F diet to remove any effects of parity order on sex ratio. Maternal body condition score (BCS), plasma hormone and metabolite concentrations were also assessed throughout the study and related to diet. Results In total 129 conceptuses were recovered. Ewes on the F diet produced significantly more male than female conceptuses (proportion male = 0.69; deviation from expected ratio of 0.5, P < 0.001). Conceptus IFNT production was unaffected by diet (P > 0.1), but positively correlated with maternal body condition score (P < 0.05), and was higher (P < 0.05) in female than male conceptuses after 4 h culture. Maternal plasma hormone and metabolite concentrations, especially progesterone and fatty acid, were also modulated by diet. Conclusion These results provide evidence that maternal diet, in the form of increased amounts of rumen-protected PUFA fed around conception, rather than maternal body condition, can skew the sex ratio towards males. These observations may have implications to
Gene-diet interactions with polymorphisms of the MGLL gene on plasma low-density lipoprotein cholesterol and size following an omega-3 polyunsaturated fatty acid supplementation: a clinical trial.

PubMed

Ouellette, Catherine; Rudkowska, Iwona; Lemieux, Simone; Lamarche, Benoit; Couture, Patrick; Vohl, Marie-Claude

2014-05-24

Omega-3 (n-3) polyunsaturated fatty acid (PUFA) consumption increases low-density lipoprotein (LDL) cholesterol (C) concentrations and particle size. Studies showed that individuals with large, buoyant LDL particles have decreased risk of cardiovascular diseases. However, a large inter-individual variability is observed in LDL particle size. Genetic factors may explain the variability of LDL-C concentrations and particle size after an n-3 PUFA supplementation. The monoglyceride lipase (MGLL) enzyme, encoded by the MGLL gene, plays an important role in lipid metabolism, especially lipoprotein metabolism. The aim of this study was to investigate if polymorphisms (SNPs) of the MGLL gene influence the variability of LDL-C and LDL particle size in response to an n-3 PUFA supplementation. 210 subjects completed the study. They consumed 5 g/d of a fish oil supplement (1.9-2.2 g eicosapentaenoic acid and 1.1 g docosaexaenoic acid) during 6 weeks. Plasma lipids were measured before and after the supplementation period and 18 SNPs of the MGLL gene, covering 100% of common genetic variations (minor allele frequency ≥0.05), have been genotyped using TaqMan technology (Life Technologies Inc., Burlington, ON, CA). Following the n-3 PUFA supplementation, 55% of subjects increased their LDL-C levels. In a model including the supplementation, genotype and supplementation*genotype effects, gene-diet interaction effects on LDL-C concentrations (rs782440, rs6776142, rs555183, rs6780384, rs6787155 and rs1466571) and LDL particle size (rs9877819 and rs13076593) were observed for the MGLL gene SNPs (p < 0.05). SNPs within the MGLL gene may modulate plasma LDL-C levels and particle size following an n-3 PUFA supplementation. This trial was registered at clinicaltrials.gov as NCT01343342.
Comparison of lipid content and Fatty Acid composition in the edible meat of wild and cultured freshwater and marine fish and shrimps from china.

PubMed

Li, Guipu; Sinclair, Andrew J; Li, Duo

2011-03-09

The lipid content and fatty acid composition in the edible meat of twenty-nine species of wild and cultured freshwater and marine fish and shrimps were investigated. Both the lipid content and fatty acid composition of the species were specified due to their unique food habits and trophic levels. Most of the marine fish demonstrated higher lipid content than the freshwater fish, whereas shrimps had the lowest lipid content. All the marine fish and shrimps had much higher total n-3 PUFA than n-6 PUFA, while most of the freshwater fish and shrimps demonstrated much lower total n-3 PUFA than n-6 PUFA. This may be the biggest difference in fatty acid composition between marine and freshwater species. The cultured freshwater fish demonstrated higher percentages of total PUFA, total n-3 PUFA, and EPA + DHA than the wild freshwater fish. Two freshwater fish, including bighead carp and silver carp, are comparable to the marine fish as sources of n-3 PUFA.
Sea cucumber and blue mussel: new sources of phospholipid enriched omega-3 fatty acids with a potential role in 3T3-L1 adipocyte metabolism.

PubMed

Vaidya, Hitesh; Cheema, Sukhinder K

2014-12-01

Omega (n)-3 polyunsaturated fatty acids (PUFA), namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are known to reduce the risk of insulin resistance and ameliorate obesity-associated disorders. DHA and EPA structured in the phospholipid form possess superior biological effects compared to the triglyceride form available in fish oil. In this study, we have found that sea cucumber (SC) and blue mussel (BM) from Newfoundland and Labrador are rich sources of n-3 PUFA structured in the phospholipid form. Treatment with SC and BM methanolic extracts (250 and 100 μg mL(-1), respectively) significantly (p < 0.01) increased triglyceride accumulation in 3T3-L1 adipocytes, along with an increase in the mRNA expression of the peroxisome proliferator-activated receptor-γ (37 and 39%, respectively) and adiponectin (57 and 56%, respectively) compared with control cells (p < 0.05). Only SC extracts (250 μg mL(-1)) increased the mRNA expression of sterol regulatory element-binding protein-1 (SREBP-1). Treatment with higher concentrations of SC and BM extracts (500 and 750 μg mL(-1), respectively) significantly (p < 0.01) decreased triglyceride accumulation in 3T3-L1 cells as opposed to an increase in triglyceride accumulation at lower concentrations. This was due to inhibition of acetyl-CoA carboxylase-1 and SREBP-1 mRNA expression compared to control cells (p < 0.05). There was no effect of the extracts on the mRNA expression of hormone sensitive lipase or lipolysis, suggesting that the decrease in triglyceride accumulation at higher concentrations is not due to breakdown and release of fat. This is the first report to show that SC and BM are new sources of phospholipid bonded n-3 PUFA, with the potential to target insulin resistance and obesity.

Relations of plasma polyunsaturated Fatty acids with blood pressures during the 26th and 28th week of gestation in women of Chinese, Malay, and Indian ethnicity.

PubMed

Lim, Wai-Yee; Chong, Mary; Calder, Philip C; Kwek, Kenneth; Chong, Yap-Seng; Gluckman, Peter D; Godfrey, Keith M; Saw, Seang-Mei; Pan, An

2015-03-01

Observational and intervention studies have reported inconsistent results of the relationship between polyunsaturated fatty acids (PUFAs) and hypertension during pregnancy. Here, we examined maternal plasma concentrations of n-3 and n-6 PUFAs between the 26th and the 28th week of gestation in relation to blood pressures and pregnancy-associated hypertension.We used data from a birth cohort study of 751 Chinese, Malay, and Indian women. Maternal peripheral systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken from the brachial arm, and central SBP and pulse pressures (PPs) were derived from radial artery pressure waveforms between the 26th and the 28th week of gestation. Pregnancy-associated hypertension (including gestational hypertension and preeclampsia) was ascertained from medical records. Plasma phosphatidylcholine n-3 and n-6 PUFAs were measured by gas chromatography and expressed as percentage of total fatty acids.Peripheral SBP was inversely associated with total n-3 PUFAs [-0.51 (95% confidence interval, CI, -0.89 to -0.13) mm Hg] and long-chain n-3 PUFAs [-0.52 (CI -0.92 to -0.13) mmHg]. Similar but weaker associations were observed for central SBP and PP. Dihomo-γ-linolenic acid was marginally positively associated with peripheral SBP, central SBP, and PP, whereas linoleic acid and total n-6 PUFAs showed no significant associations with blood pressures. We identified 28 pregnancy-associated hypertension cases, and 1% increase in total n-3 PUFAs was associated with a 24% lower odds of pregnancy-associated hypertension (odds ratio 0.76; 95% CI 0.60 to 0.97). Maternal ethnicity modified the PUFAs-blood pressure relations, with stronger inverse associations with n-3 PUFAs in Chinese women, and stronger positive associations with n-6 PUFAs in Indian women (P values for interaction ranged from 0.02 to 0.07).Higher n-3 PUFAs at midgestation are related to lower maternal blood pressures and pregnancy-associated hypertension in Asian women
Plasma and erythrocyte uptake of omega-3 fatty acids from an intravenous fish oil based lipid emulsion in patients with advanced oesophagogastric cancer.

PubMed

Eltweri, A M; Thomas, A L; Fisk, H L; Arshad, A; Calder, P C; Dennison, A R; Bowrey, D J

2017-06-01

It has been demonstrated that short term intravenous (IV) administration of omega-3 polyunsaturated fatty acids (PUFAs) is more effective than oral supplementation at promoting incorporation of the bioactive omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma, blood cells and tissues. The effect of repeated short term IV infusion of omega-3 PUFAs was investigated in patients with advanced oesophagogastric cancer during palliative chemotherapy. Patients with advanced oesophagogastric cancer (n = 21) were recruited into a phase II pilot clinical trial. All patients were scheduled for an intravenous infusion of Omegaven ® (fish oil supplement containing EPA and DHA) at a rate of 2 ml/kg body weight for 4 h once a week for up to six months. Blood samples were collected to assess omega-3 PUFA uptake into plasma non-esterified fatty acids (NEFAs) and phosphatidylcholine (PC) and into red blood cell (RBC) membranes. Fatty acid profiles were analysed by gas chromatography. Twenty patients received at least one Omegaven ® treatment and were included in the analysis. Each infusion of omega-3 PUFAs resulted in increased EPA and DHA in plasma NEFAs, but there was little effect on PUFAs within plasma PC during the infusions. However, with repeated weekly infusion of omega-3 PUFAs, the EPA content of plasma PC and of RBC membranes increased. Repeated weekly omega-3 PUFA infusion is effective in enriching plasma PC and RBC membranes in EPA in patients with advanced oesophagogastric cancer receiving palliative chemotherapy. Clinical Trials.Gov NCT01870791. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status.

PubMed

Hofacer, Rylon; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Magrisso, I Jack; Benoit, Stephen C; McNamara, Robert K

2011-09-01

This study investigated the effects of perinatal dietary omega-3 (n-3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n-3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n-3 fatty acid repletion would normalize this response. Adult rats fed the n-3-free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LCn-3 fatty acid composition and reciprocal elevations in LC omega-6 (n-6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2, but not Fads1, Elovl2, or Elovl5, mRNA expression was significantly greater in n-3-deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3n-6/18:2n-6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3n-6/18:2n-6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LCn-6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n-3 fatty acids. Copyright © 2011 Elsevier Inc. All rights reserved.
TOND1 confers tolerance to nitrogen deficiency in rice

PubMed Central

Zhang, Yangjun; Tan, Lubin; Zhu, Zuofeng; Yuan, Lixing; Xie, Daoxin; Sun, Chuanqing

2015-01-01

Nitrogen (N), the most important mineral nutrient for plants, is critical to agricultural production systems. N deficiency severely affects rice growth and decreases rice yields. However, excessive use of N fertilizer has caused severe pollution to agricultural and ecological environments. The necessity of breeding of crops that require lower input of N fertilizer has been recognized. Here we identified a major quantitative trait locus on chromosome 12, Tolerance Of Nitrogen Deficiency 1 (TOND1), that confers tolerance to N deficiency in the indica cultivar Teqing. Sequence verification of 75 indica and 75 japonica cultivars from 18 countries and regions demonstrated that only 27.3% of cultivars (41 indica cultivars) contain TOND1, whereas 72.7% of cultivars, including the remaining 34 indica cultivars and all 75 japonica cultivars, do not harbor the TOND1 allele. Over-expression of TOND1 increased the tolerance to N deficiency in the TOND1-deficient rice cultivars. The identification of TOND1 provides a molecular basis for breeding rice varieties with improved grain yield despite decreased input of N fertilizers. PMID:25439309
Serum Polyunsaturated Fatty Acids and Endometriosis.

PubMed

Hopeman, Margaret M; Riley, Joan K; Frolova, Antonina I; Jiang, Hui; Jungheim, Emily S

2015-09-01

Polyunsaturated fatty acids (PUFAs) are fatty acids containing 2 or more double bonds, and they are classified by the location of the last double bond. Omega 3 (n-3) and omega 6 (n-6) PUFAs are obtained through food sources including fatty fish and seed/vegetable oils, respectively, and they are important to a number of physiologic processes including inflammation. Previous work demonstrates suppressive effects of n-3 PUFAs on endometriotic lesions in animal models and decreased risk of endometriosis among women with high n-3 PUFA intake. Thus, we sought to determine the relationship between circulating levels of PUFAs and endometriosis in women. To do this, we performed a cross-sectional study of serum PUFAs and clinical data from 205 women undergoing in vitro fertilization (IVF). Serum PUFAs were measured using liquid chromatography coupled to tandem mass spectroscopy and included n-3 PUFAs such as α-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid and n-6 PUFAs such as linoleic acid and arachidonic acid. Multivariable logistic regression was used to determine relationships between specific and total serum PUFAs and patient history of endometriosis. Women with high serum EPA levels were 82% less likely to have endometriosis compared to women with low EPA levels (odds ratio = 0.18, 95% confidence interval 0.04-0.78). © The Author(s) 2014.
42 CFR 3.108 - Correction of deficiencies, revocation, and voluntary relinquishment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Correction of deficiencies, revocation, and voluntary relinquishment. 3.108 Section 3.108 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND... the PSO may exercise its opportunity to be heard in writing to respond to the deficiencies specified...
The relevance of serum levels of long chain omega-3 polyunsaturated fatty acids and prostate cancer risk: A meta-analysis

PubMed Central

Chua, Michael E.; Sio, Maria Christina D.; Sorongon, Mishell C.; Morales, Marcelino L.

2013-01-01

Objective: Our objective was to systematically analyze the evidence for an association between serum level long chain omega-3 polyunsaturated fatty acid (n-3 PUFA) and prostate cancer risk from human epidemiological studies. Study Procedures: We searched biomedical literature databases up to November 2011 and included epidemiological studies with description of long chain n-3 PUFA and incidence of prostate cancer in humans. Critical appraisal was done by two independent reviewers. Data were pooled using the general variance-based method with random-effects model; effect estimates were expressed as risk ratio with 95% confidence interval (CI). Heterogeneity was assessed by Chi2 and quantified by I2, publication bias was also determined. Results: In total, 12 studies were included. Significant negative association was noted between high serum level of n-3 PUFA doc-osapentaenoic acid (DPA) and total prostate cancer risk (RR:0.756; 95% CI 0.599, 0.955; p = 0.019). Likewise, a positive association between high blood level of fish oil contents, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and high-grade prostate tumour incidence (RR:1.381; 95% CI 1.050, 1.817; p = 0.021) was noted; however, this finding was evident only after adjustment was done on interstudy variability through the removal of a lower quality study from the pool. Conclusions: High serum levels of long chain n-3 PUFA DPA is associated with reduced total prostate cancer risk. While high blood level of EPA and DHA is possibly associated with increased high-grade prostate tumour risk. PMID:23766835
Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2

PubMed Central

Parkinson, Eric Kenneth

2013-01-01

The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs)—eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA)—inhibit cancer formation in vivo, but their mechanism of action is unclear. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibition have both been associated with the induction of tumour cell apoptosis by n-3 PUFAs. We show here that low doses of EPA, in particular, inhibited the growth of premalignant and malignant keratinocytes more than the growth of normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines, but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478 or an EGFR-blocking antibody inhibited ERK1/2 phosphorylation, and the blocking antibody partially antagonized growth inhibition by EPA but not by DHA. DHA generated more reactive oxygen species and activated more c-jun N-terminal kinase than EPA, potentially explaining its increased toxicity to normal keratinocytes. Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signalling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supraoptimal level, supporting the chemopreventive potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA function in vivo. PMID:23892603
Polychlorinated biphenyls (PCBs) contamination and aryl hydrocarbon receptor (AhR) agonist activity of Omega-3 polyunsaturated fatty acid supplements: implications for daily intake of dioxins and PCBs.

PubMed

Bourdon, J A; Bazinet, T M; Arnason, T T; Kimpe, L E; Blais, J M; White, P A

2010-11-01

Omega-3 polyunsaturated fatty acid (n-3 PUFA) rich oils derived primarily from fish are frequently consumed as supplements. Due to the tendency of persistent organic pollutants (POPs) to accumulate in exposed organisms, n-3 PUFA supplements can contain sufficient POPs to present a risk to consumers. Here we investigated PCB concentrations and aryl hydrocarbon receptor (AhR) agonist activity in 17 n-3 PUFA supplements available in Canada. PCBs ranged from <0.8 to 793 ng g(-1) oil, with salmon- and seal-derived products yielding the highest values. AhR agonist activity from a reporter gene assay ranged from 1.3 to 72.2 pg TEQ g(-1) oil, with salmon and tuna yielding the highest values. When consumed at the recommended doses and as a supplement to the average Canadian diet, seal-derived oil can contribute to exceedance of the tolerable daily intake of 20 ng PCBs kg-BW(-1)day(-1), and salmon-, tuna-, and sea herring-derived oils can contribute to exceedance of the tolerable daily intake limit of 2.3 pg TEQ kg-BW(-1)day(-1). The beneficial properties of fish and n-3 PUFA supplements, and the results of this study suggest that it is prudent to consume supplements derived from small, cold-water fatty fish. Further research will be necessary to draw firm conclusions. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.
Prognosis of physiological disorders in physic nut to N, P, and K deficiency during initial growth.

PubMed

Santos, Elcio Ferreira; Macedo, Fernando Giovannetti; Zanchim, Bruno José; Lima, Giuseppina Pace Pereira; Lavres, José

2017-06-01

The description of physiological disorders in physic nut plants deficient in nitrogen (N), phosphorus (P) and potassium (K) may help to predict nutritional imbalances before the appearance of visual symptoms and to guide strategies for early nutrient supply. The aim of this study was to evaluate the growth of physic nuts (Jatropha curcas L.) during initial development by analyzing the gas exchange parameters, nutrient uptake and use efficiency, as well as the nitrate reductase and acid phosphatase activities and polyamine content. Plants were grown in a complete nutrient solution and solutions from which N, P or K was omitted. The nitrate reductase activity, phosphatase acid activity, polyamine content and gas exchange parameters from leaves of N, P and K-deficient plants indicates earlier imbalances before the appearance of visual symptoms. Nutrient deficiencies resulted in reduced plant growth, although P- and K-deficient plants retained normal net photosynthesis (A), stomatal conductance (g s ) and instantaneous carboxylation efficiency (k) during the first evaluation periods, as modulated by the P and K use efficiencies. Increased phosphatase acid activity in P-deficient plants may also contribute to the P use efficiency and to A and gs during the first evaluations. Early physiological and biochemical evaluations of N-, P- and K-starved plants may rely on reliable, useful methods to predict early nutritional imbalances. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial.

PubMed

Mozaffarian, Dariush; Marchioli, Roberto; Macchia, Alejandro; Silletta, Maria G; Ferrazzi, Paolo; Gardner, Timothy J; Latini, Roberto; Libby, Peter; Lombardi, Federico; O'Gara, Patrick T; Page, Richard L; Tavazzi, Luigi; Tognoni, Gianni

2012-11-21

Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results. To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF. The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first. Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events. At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231
n-3 fatty acids: role in neurogenesis and neuroplasticity.

PubMed

Crupi, R; Marino, A; Cuzzocrea, S

2013-01-01

Omega-3 polyunsaturated fatty acids (PUFA) are essential unsaturated fatty acids with a double bond (C=C) starting after the third carbon atom from the end of the carbon chain. They are important nutrients but, unfortunately, mammals cannot synthesize them, whereby they must be obtained from food sources or from supplements. Amongst nutritionally important polyunsaturated n-3 fatty acids, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are highly concentrated in the brain and have anti-oxidative stress, anti-inflammatory and antiapoptotic effects. They are involved in many bodily processes and may reportedly lead to neuron protection in neurological diseases. aged or damaged neurons and in Alzheimer's disease. Their effect in cognitive and behavioral functions and in several neurological and psychiatric disorders has been also proven. The dentate gyrus (DG), a sub-region of hippocampus, is implicated in cognition and mood regulation. The hippocampus represents one of the two areas in the mammalian brain in which adult neurogenesis occurs. This process is associated with beneficial effects on cognition, mood and chronic pharmacological treatment. The exposure to n-3 fatty acids enhances adult hippocampal neurogenesis associated with cognitive and behavioral processes, promotes synaptic plasticity by increasing long-term potentiation and modulates synaptic protein expression to stimulate the dendritic arborization and new spines formation. On this basis we review the effect of n-3 fatty acids on adult hippocampal neurogenesis and neuroplasticity. Moreover their possible use as a new therapeutic approach for neurodegenerative diseases is pointed out.
Hnf4α is involved in the regulation of vertebrate LC-PUFA biosynthesis: insights into the regulatory role of Hnf4α on expression of liver fatty acyl desaturases in the marine teleost Siganus canaliculatus.

PubMed

Wang, Shuqi; Chen, Junliang; Jiang, Danli; Zhang, Qinghao; You, Cuihong; Tocher, Douglas R; Monroig, Óscar; Dong, Yewei; Li, Yuanyou

2018-06-01

Long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis is an important metabolic pathway in vertebrates, especially fish, considering they are the major source of n-3 LC-PUFA in the human diet. However, most fish have only limited capability for biosynthesis of LC-PUFA. The rabbitfish (Siganus canaliculatus) is able to synthesize LC-PUFA as it has all the key enzyme activities required including Δ6Δ5 Fads2, Δ4 Fads2, Elovl5, and Elovl4. We previously reported a direct interaction between the transcription factor Hnf4α and the promoter regions of Δ4 and Δ6Δ5 Fads2, which suggested that Hnf4α was involved in the transcriptional regulation of fads2 in rabbitfish. For functionally investigating it further, a full-length cDNA of 1736-bp-encoding rabbitfish Hnf4α with 454 amino acids was cloned, which was highly expressed in intestine, followed by liver and eyes. Similar to the expression characteristics of its target genes Δ4 and Δ6Δ5 fads2, levels of hnf4α mRNA in liver and eyes were higher in fish reared at low salinity than those reared in high salinity. After the rabbitfish primary hepatocytes were, respectively, incubated with alverine, benfluorex or BI6015, which were anticipated agonists or antagonist for Hnf4α, the mRNA level of Δ6Δ5 and Δ4 fads2 displayed a similar change tendency with that of hnf4α mRNA. Furthermore, when the mRNA level of hhf4α was knocked down using siRNA, the expression of Δ6Δ5 and Δ4 fads2 also decreased. Together, these data suggest that Hnf4α is involved in the transcriptional regulation of LC-PUFA biosynthesis, specifically, by targeting Δ4 and Δ6Δ5 fads2 in rabbitfish.
Omega-3 Fatty Acids and Cardiovascular Disease: Are There Benefits?

PubMed

Bowen, Kate J; Harris, William S; Kris-Etherton, Penny M

2016-11-01

Early secondary prevention trials of fish and omega-3 polyunsaturated fatty acid (PUFA) capsules reported beneficial effects on cardiovascular disease (CVD) outcomes, including all-cause mortality and sudden cardiac death. These clinical findings, as well as observational and experimental data, demonstrated that omega-3 PUFAs reduced the risk of coronary outcomes and overall mortality and were the basis for recommendations made in the early 2000s to increase omega-3 PUFA intake. In the last 6 years, however, results from both primary and secondary prevention trials have generally failed to show a beneficial effect of omega-3 PUFA supplementation, bringing current recommendations into question. Several possible reasons for these null findings have been proposed, including short treatment periods, relatively low doses of omega-3 PUFAs, small sample sizes, higher background omega-3 intakes, and the concurrent use of modern pharmacotherapy for CVD prevention. At least one of these caveats is being assessed in major clinical trials, with two omega-3 PUFA pharmacological agents being tested at doses of 4 g/day (instead of the more common <1 g/day). These null findings, however, do not necessarily mean that omega-3 PUFAs "are ineffective" in general, only that they were not effective in the context in which they were tested. Accordingly, higher intakes of omega-3 PUFAs, either from fatty fish or from supplements, if continued for decades (as the epidemiological data support) are likely to contribute towards lower risk for CVD. At this time, evidence supports the consumption of a healthy dietary pattern with at least two servings per week of fatty fish. Omega-3 PUFA supplementation is a reasonable alternative for those who do not consume fish, although fish is the preferred source of omega-3 PUFAs because it also provides additional nutrients, some of which are often under-consumed.
Effects of dietary n-3 fatty acids on the phospholipid molecular species of monkey brain.

PubMed

Lin, D S; Connor, W E; Anderson, G J; Neuringer, M

1990-10-01

We examined the changes in the molecular species of brain ethanolamine glycerophospholipids of monkeys fed diets containing widely ranging amounts of n-3 fatty acids. Two groups of rhesus monkeys were fed pre- and postnatally either a control diet (soy oil; containing 8% of fatty acids as 18:3n-3) or a deficient diet (safflower oil; containing less than 0.3% 18:3n-3). The brains of these animals were analyzed at 22 months of age. A third group of monkeys was fed the safflower oil diet to 22 months of age and then switched to a fish oil diet (28% long-chain n-3 fatty acids) for 1-2 years before autopsy. The molecular species of the diacyl, alkylacyl, and alkenylacyl ethanolamine glycerophospholipids from frontal cortex were separated by HPLC. A total of 24 molecular species were identified. Fatty acids in the sn-2 position differed markedly among the diet groups, but the sn-1 position always contained only 16:0, 18:0, or 18:1. In the diacyl subclass of the control brain, the n-3 molecular species represented 41% of total and the n-6 species 45%, whereas in the deficient brain the n-3 molecular species decreased to 9% and n-6 molecular species increased to 77%. The fatty acid 22:5n-6 did not replace 22:6n-3 in a symmetrical fashion in the molecular species of the deficient brain. In the brains of the fish oil-fed monkeys, the n-3 molecular species amounted to 61% and n-6 molecular species were reduced to 25%. The species 18:1-22:6, 16:0-22:6, and 18:0-22:6 generally changed proportionally in response to diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Stearidonic and γ-linolenic acids in echium oil improves glucose disposal in insulin resistant monkeys.

PubMed

Kavanagh, K; Flynn, D M; Jenkins, K A; Wilson, M D; Chilton, F H

2013-07-01

Echium oil (EO) contains stearidonic acid (18:4), a n-3 polyunsaturated fatty acids (PUFAs), and gamma-linolenic acids (18:3), a n-6 PUFA that can be converted to long chain (LC)-PUFAs. We aimed to compare a safflower oil (SO)-enriched diet to EO- and fish oil (FO)-enriched diets on circulating and tissue PUFAs levels and glycemic, inflammatory, and cardiovascular health biomarkers in insulin resistant African green monkeys. In a Latin-square cross-over study, eight monkeys consumed matched diets for 6 weeks with 3-week washout periods. Monkeys consuming FO had significantly higher levels of n-3 LC-PUFAs and EO supplementation resulted in higher levels of circulating n-3 LC-PUFAs and a significant increase in dihomo-gamma linolenic acid (DGLA) in red blood cells and muscle. Glucose disposal was improved after EO consumption. These data suggest that PUFAs in EO supplementation have the capacity to alter circulating, RBC and muscle LC-PUFA levels and improve glucose tolerance in insulin-resistant monkeys. Copyright © 2013 Elsevier Ltd. All rights reserved.
Dietary n-6:n-3 ratio and Vitamin E improve motility characteristics in association with membrane properties of boar spermatozoa.

PubMed

Liu, Qing; Zhou, Yuan-Fei; Duan, Run-Jia; Wei, Hong-Kui; Peng, Jian; Jiang, Si-Wen

2017-01-01

This study was aimed to evaluate the effects of dietary n-6:n-3 ratio and Vitamin E on the membrane properties and motility characteristics of spermatozoa in boars. Forty Duroc boars were randomly distributed in a 2 × 2 factorial design with two n-6:n-3 ratios (14.4 and 6.6) and two Vitamin E levels (200 and 400 mg kg-1 ). During 16 weeks of treatment, fresh semen was collected at weeks 0, 8, 12, and 16 for measurements of motility characteristics, contents of fatty acids, membrane properties (membrane fluidity and membrane integrity), and lipid peroxidation of the spermatozoa. The semen was diluted in Beltsville Thawing Solution (BTS) extender and stored at 17°C, and the sperm motility was assessed at 12, 36, 72, and 120 h of storage. The 6.6 n-6:n-3 dietary ratio increased the contents of n-3 polyunsaturated fatty acids (PUFAs) and docosahexaenoic acid (DHA) and improved the membrane integrity and membrane fluidity of the spermatozoa, resulting in notably increased total motility, sperm progressive motility, and velocity parameters of fresh semen. Feeding diet with Vitamin E (400 mg kg-1 ) prevented sperm lipid peroxidation, and resulted in higher total motility and sperm progressive motility in fresh and liquid stored semen. In conclusion, the adjustment of n-6:n-3 ratio (6.6) and supply of Vitamin E (400 mg kg-1 ) successfully improved sperm motility characteristics and thus may be beneficial to the fertility of boars, which might be due to the modification of the physical and functional properties of spermatozoa membrane in response to dietary supplementation.
Dietary n-6:n-3 ratio and Vitamin E improve motility characteristics in association with membrane properties of boar spermatozoa

PubMed Central

Liu, Qing; Zhou, Yuan-Fei; Duan, Run-Jia; Wei, Hong-Kui; Peng, Jian; Jiang, Si-Wen

2017-01-01

This study was aimed to evaluate the effects of dietary n-6:n-3 ratio and Vitamin E on the membrane properties and motility characteristics of spermatozoa in boars. Forty Duroc boars were randomly distributed in a 2 × 2 factorial design with two n-6:n-3 ratios (14.4 and 6.6) and two Vitamin E levels (200 and 400 mg kg−1). During 16 weeks of treatment, fresh semen was collected at weeks 0, 8, 12, and 16 for measurements of motility characteristics, contents of fatty acids, membrane properties (membrane fluidity and membrane integrity), and lipid peroxidation of the spermatozoa. The semen was diluted in Beltsville Thawing Solution (BTS) extender and stored at 17°C, and the sperm motility was assessed at 12, 36, 72, and 120 h of storage. The 6.6 n-6:n-3 dietary ratio increased the contents of n-3 polyunsaturated fatty acids (PUFAs) and docosahexaenoic acid (DHA) and improved the membrane integrity and membrane fluidity of the spermatozoa, resulting in notably increased total motility, sperm progressive motility, and velocity parameters of fresh semen. Feeding diet with Vitamin E (400 mg kg−1) prevented sperm lipid peroxidation, and resulted in higher total motility and sperm progressive motility in fresh and liquid stored semen. In conclusion, the adjustment of n-6:n-3 ratio (6.6) and supply of Vitamin E (400 mg kg−1) successfully improved sperm motility characteristics and thus may be beneficial to the fertility of boars, which might be due to the modification of the physical and functional properties of spermatozoa membrane in response to dietary supplementation. PMID:26763547
Significant Enrichment of Polyunsaturated Fatty Acids (PUFAs) in the Lipids Extracted by Supercritical CO2 from the Livers of Australian Rock Lobsters (Jasus edwardsii).

PubMed

Nguyen, Trung T; Zhang, Wei; Barber, Andrew R; Su, Peng; He, Shan

2015-05-13

Australian rock lobster (Jasus edwardsii) liver contains approximately 24.3% (w/w) lipids, which can contain a high amount of polyunsaturated fatty acids (PUFAs). However, this material has been found to be contaminated with arsenic (240 mg/kg) and cadmium (8 mg/kg). The high level of contaminants in the raw material and the large amount of PUFAs in the lipids prove a significant challenge in the extraction of high-quality lipids from this byproduct by conventional methods. Supercritical carbon dioxide (SC-CO2) extraction is a highly promising technology for lipid extraction with advantages including low contamination and low oxidation. The technique was optimized to achieve nearly 94% extraction of lipids relative to conventional Soxhlet extraction in Australian rock lobster liver at conditions of 35 MPa and 50 °C for 4 h. The extracted lipids are significantly enriched in PUFAs at 31.3% of total lipids, 4 times higher than those in the lipids recovered by Soxhlet extraction (7.8%). Specifically, the concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in SC-CO2 extraction are 7 times higher than those obtained by Soxhlet extraction. Moreover, very small amounts of toxic heavy metals such as lead (Pb), arsenic (As), mercury (Hg), and cadmium (Cd) were detected in the SC-CO2-extracted lipids, 0.5-27 times lower than those in the Soxhlet-extracted lipids, which are 40-200 times lower than the regulatory limit maximum values. The low levels of contaminants and the high proportion of PUFAs (dominated by DHA and EPA) found in the SC-CO2-extracted lipids from Australian rock lobster liver suggest that the material could potentially be used as a valuable source of essential fatty acids for human consumption.
Effects of n-3 Polyunsaturated Fatty Acid Supplementation on Serum Leptin Levels, Appetite Sensations, and Intake of Energy and Macronutrients in Obese People: A Randomized Clinical Trial.

PubMed

Payahoo, L; Ostadrahimi, A; Farrin, N; Khaje-Bishak, Y

2017-10-05

Obesity is a common health problem. Appetite is one of the main obesity-controlling factors that can be influenced by leptin. Leptin reduces food intake and accelerates energy expenditure. Leptin levels can be affected by dietary factors such as fats, special amino acids, and fructose. This study aimed to determine the effects of polyunsaturated fatty acid n-3 (PUFA n-3) supplementation on serum leptin levels, appetite sensations, and dietary intakes in obese people. This study was performed on 60 obese individuals with body mass index (BMI) 30 (kg/m 2 ) and above in 2012 in Tabriz, Iran. The participants were randomly allocated to the intervention (consumed two capsules containing 1 g/day n-3 fatty acids [180 mg EPA, 120 mg DHA] for 4 weeks) and control groups. Serum leptin levels were assessed by ELISA method, and visual analogue scale (VAS) questionnaire was completed for evaluating appetite sensations. The mean caloric [before = 1,575.39 (600), after = 1,236.14 (448.40)] and macronutrient intakes were decreased significantly in the intervention group (p < .05). After adjusting for baseline serum leptin levels, age, and gender values, the fullness item significantly increased in the intervention group [before = 2 (1-5), after = 3 (1-5), p = .034]. In addition, BMI decreased and serum leptin levels increased nonsignificantly in the intervention group. According to the results, PUFA n-3 decreased energy and macronutrient intakes, probably through the modulating of satiety. The short period of study caused the nonsignificant changes in BMI and circulatory leptin. Further studies are needed to confirm these results.

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