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

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.

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.

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.

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.

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.

Consumption of Red Meat, but Not Cooking Oils High in Polyunsaturated Fat, Is Associated with Higher Arachidonic Acid Status in Singapore Chinese Adults.

PubMed

Seah, Jowy Yi Hoong; Gay, Gibson Ming Wei; Su, Jin; Tai, E-Shyong; Yuan, Jian-Min; Koh, Woon-Puay; Ong, Choon Nam; van Dam, Rob M

2017-01-31

High arachidonic acid (AA; 20:4 n - 6) status may have adverse effects on inflammation and risk of cardiovascular diseases. Concerns about high intake of n - 6 polyunsaturated fatty acids (PUFAs) are based on the premise that endogenous conversion from linoleic acid (LA; 18:2 n - 6) is an important source of AA, but few population-based studies have investigated dietary determinants of AA status. In this study, we examined habitual food consumption in relation to plasma concentrations of AA and other PUFAs in population-based studies. We used cross-sectional data from 269 healthy, ethnic Chinese participants (25-80 years old) with contrasting intakes of fish and red meat from the Singapore Prospective Study Program and 769 healthy participants (44-74 years old) from the Singapore Chinese Health Study as a validation set. Multivariable linear regression was used to examine PUFA intake (% energy) and food sources of PUFA (fish, red meat, poultry, soy and cooking oils) in relation to plasma PUFAs (AA, LA, dihomo-gamma-linolenic acid (DGLA; 20:3 n - 6), alpha-linolenic acid (ALA; 18:3 n - 3), eicosapentaenoic acid (EPA; 20:5 n - 3), and docosahexaenoic acid (DHA; 22:6 n - 3)) concentrations. Higher intake of red meat was associated with higher plasma AA concentrations. High intake of PUFA or PUFA-rich oils was associated with higher plasma ALA but not with plasma AA. Higher intakes of soy were associated with higher ALA and fish with higher DHA and EPA concentrations. These associations were statistically significant (p < 0.05) in both studies. Red meat consumption, but not PUFA or PUFA-rich cooking oil, was associated with circulating AA suggesting that intake of pre-formed AA rather than LA is an important determinant of AA status. A diet high in fish, soy products and polyunsaturated cooking oil, and low in red meat may be associated with an optimal plasma profile of PUFA in this Chinese population.

Consumption of Red Meat, but Not Cooking Oils High in Polyunsaturated Fat, Is Associated with Higher Arachidonic Acid Status in Singapore Chinese Adults

PubMed Central

Seah, Jowy Yi Hoong; Gay, Gibson Ming Wei; Su, Jin; Tai, E-Shyong; Yuan, Jian-Min; Koh, Woon-Puay; Ong, Choon Nam; van Dam, Rob M.

2017-01-01

High arachidonic acid (AA; 20:4n-6) status may have adverse effects on inflammation and risk of cardiovascular diseases. Concerns about high intake of n-6 polyunsaturated fatty acids (PUFAs) are based on the premise that endogenous conversion from linoleic acid (LA; 18:2n-6) is an important source of AA, but few population-based studies have investigated dietary determinants of AA status. In this study, we examined habitual food consumption in relation to plasma concentrations of AA and other PUFAs in population-based studies. We used cross-sectional data from 269 healthy, ethnic Chinese participants (25–80 years old) with contrasting intakes of fish and red meat from the Singapore Prospective Study Program and 769 healthy participants (44–74 years old) from the Singapore Chinese Health Study as a validation set. Multivariable linear regression was used to examine PUFA intake (% energy) and food sources of PUFA (fish, red meat, poultry, soy and cooking oils) in relation to plasma PUFAs (AA, LA, dihomo-gamma-linolenic acid (DGLA; 20:3n-6), alpha-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3), and docosahexaenoic acid (DHA; 22:6n-3)) concentrations. Higher intake of red meat was associated with higher plasma AA concentrations. High intake of PUFA or PUFA-rich oils was associated with higher plasma ALA but not with plasma AA. Higher intakes of soy were associated with higher ALA and fish with higher DHA and EPA concentrations. These associations were statistically significant (p < 0.05) in both studies. Red meat consumption, but not PUFA or PUFA-rich cooking oil, was associated with circulating AA suggesting that intake of pre-formed AA rather than LA is an important determinant of AA status. A diet high in fish, soy products and polyunsaturated cooking oil, and low in red meat may be associated with an optimal plasma profile of PUFA in this Chinese population. PMID:28146136

Omega-6 polyunsaturated fatty acids, serum zinc, delta-5- and delta-6-desaturase activities and incident metabolic syndrome.

PubMed

Yary, T; Voutilainen, S; Tuomainen, T-P; Ruusunen, A; Nurmi, T; Virtanen, J K

2017-08-01

The associations of n-6 polyunsaturated fatty acids (PUFA) with metabolic syndrome have been poorly explored. We investigated the associations of the serum n-6 PUFA and the activities of enzymes involved in the PUFA metabolism, delta-5-desaturase (D5D) and delta-6-desaturase (D6D) with risk of incident metabolic syndrome. We also investigated whether zinc, a cofactor for these enzymes, modifies these associations. A prospective follow-up study was conducted on 661 men who were aged 42-60 years old at baseline in 1984-1989 and who were re-examined in 1998-2001. Men in the highest versus the lowest serum total omega-6 PUFA tertile had a 70% lower multivariate-adjusted risk of incident metabolic syndrome [odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.18-0.51, P trend < 0.001]. Inverse associations were also observed for linoleic acid, arachidonic acid and D5D activity. By contrast, men in the highest tertile of D6D activity had an 84% higher risk (OR = 1.84; 95% CI = 1.15-2.94, P trend = 0.008). Similar associations were observed with many of the metabolic syndrome components at the re-examinations. Most associations were attenuated after adjustment for body mass index. Finally, the associations of D6D and LA were stronger among those with a higher serum zinc concentration. Higher serum total n-6 PUFA, linoleic acid and arachidonic acid concentrations and D5D activity were associated with a lower risk of developing metabolic syndrome and higher D6D activity was associated with a higher risk. The role of zinc also needs to be investigated in other populations. © 2016 The British Dietetic Association Ltd.

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.

IMAGING BRAIN SIGNAL TRANSDUCTION AND METABOLISM VIA ARACHIDONIC AND DOCOSAHEXAENOIC ACID IN ANIMALS AND HUMANS

PubMed Central

Basselin, Mireille; Ramadan, Epolia; Rapoport, Stanley I.

2012-01-01

The polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), important second messengers in brain, are released from membrane phospholipid following receptor-mediated activation of specific phospholipase A2 (PLA2) enzymes. We developed an in vivo method in rodents using quantitative autoradiography to image PUFA incorporation into brain from plasma, and showed that their incorporation rates equal their rates of metabolic consumption by brain. Thus, quantitative imaging of unesterified plasma AA or DHA incorporation into brain can be used as a biomarker of brain PUFA metabolism and neurotransmission. We have employed our method to image and quantify effects of mood stabilizers on brain AA/DHA incorporation during neurotransmission by muscarinic M1,3,5, serotonergic 5-HT2A/2C, dopaminergic D2-like (D2, D3, D4) or glutamatergic N-methyl-D-aspartic acid (NMDA) receptors, and effects of inhibition of acetylcholinesterase, of selective serotonin and dopamine reuptake transporter inhibitors, of neuroinflammation (HIV-1 and lipopolysaccharide) and excitotoxicity, and in genetically modified rodents. The method has been extended for the use with positron emission tomography (PET), and can be employed to determine how human brain AA/DHA signaling and consumption are influenced by diet, aging, disease and genetics. PMID:22178644

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.

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

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

Ligand-independent activation of EphA2 by arachidonic acid induces metastasis-like behaviour in prostate cancer cells

PubMed Central

Tawadros, T; Brown, M D; Hart, C A; Clarke, N W

2012-01-01

Background: High intake of omega-6 polyunsaturated fatty acids (PUFA) has been associated with clinical progression in prostate cancer (CaP). This study investigates the signalling mechanism by which the omega-6 PUFA arachidonic acid (AA) induces prostatic cellular migration to bone marrow stroma. Methods: Western blot analysis of the PC-3, PC3-GFP, DU 145 and LNCaP cells or their lipid raft (LR) components post AA stimulation was conducted in association with assays for adhesion and invasion through the bone marrow endothelial monolayers. Results: Arachidonic acid increased transendothelial migration of PC3-GFP cells (adhesion 37%±0.08, P=0.0124; transmigration 270%±0.145, P=0.0008). Akt, Src and focal adhesion kinase (FAK) pathways were induced by AA and integrally involved in transendothelial migration. LR were critical in AA uptake and induced Akt activity. Ephrin receptor A2 (EphA2), localised in LR, is expressed in DU 145 and PC-3 cells. Arachidonic acid induced a rapid increase of EphA2 Akt-dependent/ligand-independent activation, while knockdown of the EphrinA1 ligand decreased AA induced transendothelial migration, with an associated decrease in Src and FAK activity. Arachidonic acid activated Akt in EphA2− LNCaP cells but failed to induce BMEC transendothelial invasion. Conclusion: Arachidonic acid induced stimulation of EphA2 in vitro is associated fundamentally with CaP epithelial migration across the endothelial barrier. PMID:23037715

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

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.

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.

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.

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

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

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.

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

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

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.

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.

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

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.

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.

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...

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.

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.

Dietary DHA reduced downstream endocannabinoid and inflammatory gene expression, epididymal fat mass, and improved aspects of glucose use in muscle in C57BL/6J mice

USDA-ARS?s Scientific Manuscript database

Objective: Endocannabinoid system (ECS) overactivation is associated with increased adiposity and likely contributes to type II diabetes risk. Elevated tissue cannabinoid receptor 1 (CB1) and circulating endocannabinoids derived from the n-6 polyunsaturated acid (PUFA) arachidonic acid occur in obes...

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.

Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality: The Cardiovascular Health Study

PubMed Central

Wu, Jason HY; Lemaitre, Rozenn N; King, Irena B; Song, Xiaoling; Psaty, Bruce M; Siscovick, David S; Mozaffarian, Dariush

2014-01-01

Background While omega-6 polyunsaturated fatty acids(n-6 PUFA) have been recommended to reduce CHD, controversy remains about benefits vs. harms, including concerns over theorized pro-inflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid(LA, the major dietary PUFA), γ-linolenic acid(GLA), dihomo-γ-linolenic acid(DGLA), and arachidonic acid(AA),with total and cause-specific mortality in the Cardiovascular Health Study, a community-based US cohort. Methods and Results Among 2,792 participants(age≥65y) free of CVD at baseline, plasma phospholipid n-6 PUFAwere measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34,291 person-years of follow-up(1992–2010), 1,994 deaths occurred(678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher LA was associated with lower total mortality, with extreme-quintile HR=0.87(P-trend=0.005). Lower death was largely attributable to CVD causes, especially nonarrhythmic CHD mortality(HR=0.51, 95%CI=0.32–0.82, P-trend=0.001). Circulating GLA, DGLA, and AA were not significantly associated with total or cause-specific mortality; e.g., for AA and CHD death, the extreme-quintile HR was 0.97 (95%CI=0.70–1.34, P-trend=0.87). Evaluated semi-parametrically, LA showed graded inverse associations with total mortality(P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both. Conclusions High circulating LA, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults. PMID:25124495

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

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.

Associations With Eicosapentaenoic Acid to Arachidonic Acid Ratio and Mortality in Hospitalized Heart Failure Patients.

PubMed

Watanabe, Shunsuke; Yoshihisa, Akiomi; Kanno, Yuki; Takiguchi, Mai; Yokokawa, Tetsuro; Sato, Akihiko; Miura, Shunsuke; Shimizu, Takeshi; Abe, Satoshi; Sato, Takamasa; Suzuki, Satoshi; Oikawa, Masayoshi; Sakamoto, Nobuo; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-Ichi; Takeishi, Yasuchika

2016-12-01

Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) lowers the risk of atherosclerotic cardiovascular events, particularly ischemic heart disease. In addition, the ratio of eicosapentaenoic acid (EPA; n-3 PUFA) to arachidonic acid (AA; n-6 PUFA) has recently been recognized as a risk marker of cardiovascular disease. In contrast, the prognostic impact of the EPA/AA ratio on patients with heart failure (HF) remains unclear. A total of 577 consecutive patients admitted for HF were divided into 2 groups based on median of the EPA/AA ratio: low EPA/AA (EPA/AA <0.32 mg/dl, n = 291) and high EPA/AA (EPA/AA ≥0.32, n = 286) groups. We compared laboratory data and echocardiographic findings and followed cardiac mortality. Although body mass index, blood pressure, B-type natriuretic peptide, hemoglobin, estimated glomerular filtration rate, total protein, albumin, sodium, C-reactive protein, and left ventricular ejection fraction did not differ between the 2 groups, cardiac mortality was significantly higher in the low EPA/AA group than in the high EPA/AA group (12.7 vs 5.9%, log-rank P = .004). Multivariate Cox proportional hazard analysis revealed that the EPA/AA ratio was an independent predictor of cardiac mortality (hazard ratio 0.677, 95% confidence interval 0.453-0.983, P = .041) in patients with HF. The EPA/AA ratio was an independent predictor of cardiac mortality in patients with HF; therefore, the prognosis of patients with HF may be improved by taking appropriate management to control the EPA/AA balance. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Detection in vivo of a Novel Endogenous Etheno DNA Adduct Derived from Arachidonic Acid and the Effects of Antioxidants on Its Formation

PubMed Central

Cruz, Idalia M.; Pondicherry, Sharanya R.; Fernandez, Aileen; Schultz, Casey L.; Yang, Peiying; Pan, Jishen; Desai, Dhimant; Krzeminski, Jacek; Amin, Shantu; Christov, Plamen P.; Hara, Yukihiko; Chung, Fung-Lung

2014-01-01

Previous studies showed that the 7-(1′,2′-dihydroxyheptyl) substituted etheno DNA adducts are products from reactions with epoxide of (E)-4-hydroxy-2-nonenal (HNE), an oxidation product of ω-6 polyunsaturated fatty acids (PUFAs). In this work, we report the detection of 7-(1′,2′-dihydroxyheptyl)-1,N6-ethenodeoxyadenosine (DHHedA) in rodent and human tissues by two independent methods: a 32P-postlabeling/HPLC method and an isotope dilution liquid chromatography electrospray ionization tandem mass spectrometry method (ID-LC-ESI-MS/MS), demonstrating for the first time that DHHedA is a background DNA lesion in vivo. We showed that DHHedA can be formed upon incubation of arachidonic acid (AA) with deoxyadenosine (dA), supporting the notion that ω-6 PUFAs are the endogenous source of DHHedA formation. Because cyclic adducts are derived from the oxidation of PUFAs, we subsequently examined the effects of antioxidants, α-lipoic acid, Polyphenon E and vitamin E, on the formation of DHHedA and γ-hydroxy-1,N2-propanodeoxyguanosine (γ-OHPdG), a widely studied acrolein-derived adduct arising from oxidized PUFAs, in the livers of Long Evans Cinnamon (LEC) rats. LEC rats are inflicted with elevated lipid peroxidation and prone to the development of hepatocellular carcinomas. The results showed that while the survival of LEC rats increased significantly by α-lipoic acid, none of the antioxidants inhibited the formation of DHHedA and only Polyphenon E decreased the formation of γ-OHPdG. In contrast, vitamin E caused a significant increase in the formation of both γ-OHPdG and DHHedA in the livers of LEC rats. PMID:24816294

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.

Differences in Arachidonic Acid Levels and Fatty Acid Desaturase (FADS) Gene Variants in African Americans and European Americans with Diabetes/Metabolic Syndrome

PubMed Central

Sergeant, Susan; Hugenschmidt, Christina E.; Rudock, Megan E.; Ziegler, Julie T.; Ivester, Priscilla; Ainsworth, Hannah C.; Vaidya, Dhananjay; Case, L. Douglas; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W.; Mathias, Rasika A.; Chilton, Floyd H.

2012-01-01

Over the past 50 years, increases in dietary n-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid, have been hypothesized to cause or exacerbate chronic inflammatory diseases. This study examines an individual’s innate capacity to synthesize n-6-long chain PUFAs (LC-PUFAs), with respect to the fatty acid desaturase (FADS) locus in Americans of African and European descent with diabetes/metabolic syndrome. Compared to European Americans (EAm), African Americans (AfAm) exhibited markedly higher serum levels of arachidonic acid (AA) (EAm 7.9±2.1; AfAm 9.8±1.9 % of total fatty acids, mean ± sd; p<2.29×10−9) and the AA to n-6-precursor fatty acid ratio, which estimates FADS1 activity (EAm 5.4±2.2, AfAm 6.9±2.2; p=1.44×10−5). Seven single nucleotide polymorphisms (SNP) mapping to the FADS locus revealed strong association with AA, eicosapentaenoic acid (EPA) and dihomogamma-linolenic acid (DGLA) in the EAm. Importantly, EAm homozygous for the minor allele (T) had significantly lower AA levels (TT: 6.3±1.0; GG: 8.5±2.1; p=3.0×10−5) and AA/DGLA ratios (TT: 3.4±0.8; GG: 6.5±2.3; p=2.2×10−7) but higher DGLA levels (TT: 1.9±0.4; GG: 1.4±0.4; p=3.3×10−7) compared to those homozygous for the major allele (GG). Allele frequency patterns suggest that the GG genotype at rs174537 (associated with higher circulating levels of AA) is much higher in AfAm (0.81) compared to EAm (0.46). Similarly, marked differences in rs174537 genotypic frequencies were observed in HapMap populations. These data suggest that there are likely important differences in the capacity of different populations to synthesize LC-PUFAs. These differences may provide a genetic mechanism contributing to health disparities between populations of African and European descent. PMID:21733300

The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

PubMed Central

Carlsson, Johan A.; Wold, Agnes E.; Sandberg, Ann-Sofie; Östman, Sofia M.

2015-01-01

Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells. PMID:26619195

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 © 2012 Elsevier Inc. All rights reserved.

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.

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.

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

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.

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.

Fatty acid transfer in the food web of a coastal Mediterranean lagoon: Evidence for high arachidonic acid retention in fish

NASA Astrophysics Data System (ADS)

Koussoroplis, Apostolos-Manuel; Bec, Alexandre; Perga, Marie-Elodie; Koutrakis, Emmanuil; Bourdier, Gilles; Desvilettes, Christian

2011-02-01

The transfer of fatty acids (FAs) in the food web of a Mediterranean lagoon was studied using FA compositional patterns across several trophic levels. The structure of the food web was inferred from C and N stable isotopes values and an isotope mixing model was used in order to estimate the relative contribution of the different potential food sources to the biomass of consumers. Bidimensional plots of FA composition of food web components against their δ 15N values indicated a general trend of increasing proportions of highly unsaturated fatty acids (HUFAs) with increasing trophic levels while the proportions of saturated fatty acids (SAFAs) and 18-carbon polyunsaturated fatty acids (PUFAs) decreased. Using the relative contributions of food sources to consumers and their FA compositions, a model was built in order to estimate the PUFA composition of consumer mixed diets which was compared to consumer PUFA profiles. The latter allowed the identification of the PUFAs which were mostly enriched/retained in consumer lipids. There was a surprisingly high retention of arachidonic acid (ARA), a trend which challenges the idea of low ARA needs in marine fish and suggests the important physiological role of this essential FA for fish in estuarine environments.

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.

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.

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.

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.

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

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

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.

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.

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.

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

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.

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

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.

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.

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.

Polyunsaturated fatty acid intake and prevalence of eczema and rhinoconjunctivitis in Japanese children: The Ryukyus Child Health Study

PubMed Central

2011-01-01

Background The recent increase in the prevalence of allergic disorders might be a consequence of increased intake of n-6 polyunsaturated fatty acids (PUFAs) and reduced intake of n-3 PUFAs. The current cross-sectional study examined the association between intake levels and the prevalence of eczema and rhinoconjunctivitis in Japanese children. Methods Subjects were 23,388 schoolchildren aged 6-15 years residing in Okinawa. The presence of eczema and/or rhinoconjunctivitis was determined according to the criteria of the International Study of Asthma and Allergies in Childhood. A brief diet history questionnaire for children and adolescents was administered to acquire information on dietary factors. Adjustment was made for age, sex, residential municipality, number of siblings, smoking in the household, body mass index, paternal and maternal history of allergic diseases, and paternal and maternal educational level. Results The prevalences of eczema and rhinoconjunctivitis in the previous 12 months were 7.0% and 8.0%, respectively. Consumption of PUFAs, n-3 PUFAs, α-linolenic acid, n-6 PUFAs, and linoleic acid was positively associated with the prevalence of eczema: the adjusted odds ratios (ORs) between extreme quintiles (95% confidence intervals [CIs], P for trend) were 1.26 (1.07-1.48, 0.04), 1.31 (1.11-1.54, 0.009), 1.31 (1.12-1.55, 0.003), 1.26 (1.07-1.48, 0.01), and 1.27 (1.08-1.49, 0.01), respectively. Arachidonic acid intake was independently inversely related to eczema: the adjusted OR between extreme quintiles was 0.81 (0.69-0.95, 0.0008). Eczema was not associated with eicosapentaenoic or docosahexaenoic acid intake, or with the ratio of n-3 to n-6 PUFA intake. Only arachidonic acid intake was statistically significantly related to the prevalence of rhinoconjunctivitis, showing a clear inverse linear trend: the adjusted OR between extreme quintiles was 0.86 (0.74-0.997, 0.03). Conclusions Consumption of n-3 and n-6 PUFAs, especially α-linolenic acid and

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.

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.

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.

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.

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.

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 ...

Dietary Intakes of Arachidonic Acid and α-Linolenic Acid Are Associated with Reduced Risk of Hip Fracture in Older Adults12

PubMed Central

Farina, Emily K.; Kiel, Douglas P.; Roubenoff, Ronenn; Schaefer, Ernst J.; Cupples, L. Adrienne; Tucker, Katherine L.

2011-01-01

PUFA are hypothesized to influence bone health, but longitudinal studies on hip fracture risk are lacking. We examined associations between intakes of PUFA and fish, and hip fracture risk among older adults (n = 904) in the Framingham Osteoporosis Study. Participants (mean age ~75 y at baseline) were followed for incident hip fracture from the time they completed the baseline exam (1988–1989) until December 31, 2005. HR and 95% CI were estimated for energy-adjusted dietary fatty acid exposure variables [(n-3) fatty acids: α-linolenic acid (ALA), EPA, DHA, EPA+DHA; (n-6) fatty acids: linoleic acid, arachidonic acid (AA); and the (n-6):(n-3) ratio] and fish intake categories, adjusting for potential confounders and covariates. Protective associations were observed between intakes of ALA (P-trend = 0.02) and hip fracture risk in a combined sample of women and men and between intakes of AA (P-trend = 0.05) and hip fracture risk in men only. Participants in the highest quartile of ALA intake had a 54% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.46; 95% CI = 0.26–0.83). Men in the highest quartile of AA intake had an 80% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.20; 95% CI = 0.04–0.96). No significant associations were observed among intakes of EPA, DHA, EPA+DHA, or fish. These findings suggest dietary ALA may reduce hip fracture risk in women and men and dietary AA may reduce hip fracture risk in men. PMID:21508210

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.

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.

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

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.

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

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.

Erythrocyte polyunsaturated fatty acid status, memory, cognition and mood in older adults with mild cognitive impairment and healthy controls.

PubMed

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

2011-01-01

Polyunsaturated fatty acid (PUFA) levels are altered in adults with cognitive decline and also depression. Depression facilitates progression from mild cognitive impairment (MCI) to dementia. We investigated associations between omega-3 (n-3) and omega-6 (n-6) PUFAs and cognition, memory and depression in 50 adults ≥65 years with MCI and 29 controls. Memory, depressive symptoms and erythrocyte PUFAs (% total fatty acids) were assessed. Eicosapentaenoic acid (EPA) was lower in MCI vs controls (.94% vs 1.26%, p<.01); n-6 PUFAs were higher: dihomo-gamma-linolenic acid (1.51% vs 1.32%, p<.01), arachidonic acid (11.54% vs 10.70%, p<.01), n-6 docosapentaenoic acid (DPA:.46% vs.34%, p<.01), and total n-6 PUFA (24.14% vs 23.37%, p<.05). Higher n-6 DPA predicted poorer mental health. Lower n-3 DPA was associated with higher self-reported bodily pain. Adults with MCI had higher depression scores (3.05±.39 vs 1.33±.24, p<.01). Depressive symptoms associated with elevated n-6 PUFA may contribute to cognitive decline in this population. Copyright © 2011 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

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

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.

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.

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.

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.

Novel liquid chromatography-mass spectrometry method shows that vitamin E deficiency depletes arachidonic and docosahexaenoic acids in zebrafish (Danio rerio) embryos.

PubMed

Lebold, Katie M; Kirkwood, Jay S; Taylor, Alan W; Choi, Jaewoo; Barton, Carrie L; Miller, Galen W; La Du, Jane; Jump, Donald B; Stevens, Jan Frederik; Tanguay, Robert L; Traber, Maret G

2013-01-01

To test the hypothesis that embryogenesis depends upon α-tocopherol (E) to protect embryo polyunsaturated fatty acids (PUFAs) from lipid peroxidation, new methodologies were applied to measure α-tocopherol and fatty acids in extracts from saponified zebrafish embryos. A solid phase extraction method was developed to separate the analyte classes, using a mixed mode cartridge (reverse phase, π-π bonding, strong anion exchange), then α-tocopherol and cholesterol were measured using standard techniques, while the fatty acids were quantitated using a novel, reverse phase liquid chromatography-mass spectrometry (LC-MS) approach. We also determined if α-tocopherol status alters embryonic lipid peroxidation products by analyzing 24 different oxidized products of arachidonic or docosahexaenoic (DHA) acids in embryos using LC with hybrid quadrupole-time of flight MS. Adult zebrafish were fed E- or E+ diets for 4 months, and then were spawned to obtain E- and E+ embryos. Between 24 and 72 hours post-fertilization (hpf), arachidonic acid decreased 3-times faster in E- (21 pg/h) compared with E+ embryos (7 pg/h, P<0.0001), while both α-tocopherol and DHA concentrations decreased only in E- embryos. At 36 hpf, E- embryos contained double the 5-hydroxy-eicosatetraenoic acids and 7-hydroxy-DHA concentrations, while other hydroxy-lipids remained unchanged. Vitamin E deficiency during embryogenesis depleted DHA and arachidonic acid, and increased hydroxy-fatty acids derived from these PUFA, suggesting that α-tocopherol is necessary to protect these critical fatty acids.

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

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

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.

Non-enzymatic cyclic oxygenated metabolites of adrenic, docosahexaenoic, eicosapentaenoic and α-linolenic acids; bioactivities and potential use as biomarkers.

PubMed

Galano, Jean-Marie; Lee, Jetty Chung-Yung; Gladine, Cecile; Comte, Blandine; Le Guennec, Jean-Yves; Oger, Camille; Durand, Thierry

2015-04-01

Cyclic oxygenated metabolites are formed in vivo through non-enzymatic free radical reaction of n-6 and n-3 polyunsaturated fatty acids (PUFAs) such as arachidonic (ARA C20:4 n-6), adrenic (AdA 22:4 n-6), α-linolenic (ALA 18:3 n-3), eicosapentaenoic (EPA 20:5 n-3) and docosahexaenoic (DHA 22:6 n-3) acids. These cyclic compounds are known as isoprostanes, neuroprostanes, dihomo-isoprostanes and phytoprostanes. Evidence has emerged for their use as biomarkers of oxidative stress and, more recently, the n-3PUFA-derived compounds have been shown to mediate bioactivities as secondary messengers. Accordingly, this review will focus on the cyclic oxygenated metabolites generated from AdA, ALA, EPA and DHA. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance". Copyright © 2014 Elsevier B.V. All rights reserved.

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

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.

Omega-6 fatty acid biomarkers and incident type 2 diabetes: Pooled analysis of individual-level data for 39740 adults from 20 prospective cohort studies

USDA-ARS?s Scientific Manuscript database

The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2...

Obesity resistance and deregulation of lipogenesis in Δ6-fatty acid desaturase (FADS2) deficiency.

PubMed

Stoffel, Wilhelm; Hammels, Ina; Jenke, Britta; Binczek, Erika; Schmidt-Soltau, Inga; Brodesser, Susanne; Odenthal, Margarete; Thevis, Mario

2014-01-01

Δ-6-fatty acid desaturase (FADS2) is the key enzyme in the biosynthesis of polyunsaturated fatty acids (PUFAs), the essential structural determinants of mammalian membrane lipid-bilayers. We developed the auxotrophic fads2(-/-) mouse mutant to assess the enigmatic role of ω3- and ω6-PUFAs in lipid homeostasis, membrane structure and function. Obesity resistance is another major phenotype of the fads2(-/-) mutant, the molecular basis of which is unknown. Phospholipidomic profiling of membrane systems of fads2(-/-)mice revealed diacylglycerol-structures, deprived of PUFAs but substituted with surrogate eicosa-5,11,14-trienoic acid. ω6-Arachidonic (AA) and ω3-docosahexaenoic acid (DHA) supplemented diets transformed fads2(-/-) into AA-fads2(-/-) and DHA-fads2(-/-) mutants. Severely altered phospholipid-bilayer structures of subcellular membranes of fads2(-/-) liver specifically interfered with maturation of transcription factor sterol-regulatory-element-binding protein, the key regulator of lipogenesis and lipid homeostasis. This study strengthens the concept that specific PUFA-substituted membrane phospholipid species are critical constituents of the structural platform operative in lipid homeostasis in normal and disease conditions.

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.

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.

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.

Metabolism and phospholipid assembly of polyunsaturated fatty acids in human bone marrow mesenchymal stromal cells.

PubMed

Tigistu-Sahle, Feven; Lampinen, Milla; Kilpinen, Lotta; Holopainen, Minna; Lehenkari, Petri; Laitinen, Saara; Käkelä, Reijo

2017-01-01

High arachidonic acid (20:4n-6) and low n-3 PUFA levels impair the capacity of cultured human bone marrow mesenchymal stromal cells (hBMSCs) to modulate immune functions. The capacity of the hBMSCs to modify PUFA structures was found to be limited. Therefore, different PUFA supplements given to the cells resulted in very different glycerophospholipid (GPL) species profiles and substrate availability for phospholipases, which have preferences for polar head group and acyl chains when liberating PUFA precursors for production of lipid mediators. When supplemented with 20:4n-6, the cells increased prostaglandin E2 secretion. However, they elongated 20:4n-6 to the less active precursor, 22:4n-6, and also incorporated it into triacylglycerols, which may have limited the proinflammatory signaling. The n-3 PUFA precursor, 18:3n-3, had little potency to reduce the GPL 20:4n-6 content, while the eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acid supplements efficiently displaced the 20:4n-6 acyls, and created diverse GPL species substrate pools allowing attenuation of inflammatory signaling. The results emphasize the importance of choosing appropriate PUFA supplements for in vitro hBMSC expansion and suggests that for optimal function they require an exogenous fatty acid source providing 20:5n-3 and 22:6n-3 sufficiently, but 20:4n-6 moderately, which calls for specifically designed optimal PUFA supplements for the cultures. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

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

Novel liquid chromatography–mass spectrometry method shows that vitamin E deficiency depletes arachidonic and docosahexaenoic acids in zebrafish (Danio rerio) embryos☆

PubMed Central

Lebold, Katie M.; Kirkwood, Jay S.; Taylor, Alan W.; Choi, Jaewoo; Barton, Carrie L.; Miller, Galen W.; Du, Jane La; Jump, Donald B.; Stevens, Jan Frederik; Tanguay, Robert L.; Traber, Maret G.

2013-01-01

To test the hypothesis that embryogenesis depends upon α-tocopherol (E) to protect embryo polyunsaturated fatty acids (PUFAs) from lipid peroxidation, new methodologies were applied to measure α-tocopherol and fatty acids in extracts from saponified zebrafish embryos. A solid phase extraction method was developed to separate the analyte classes, using a mixed mode cartridge (reverse phase, π–π bonding, strong anion exchange), then α-tocopherol and cholesterol were measured using standard techniques, while the fatty acids were quantitated using a novel, reverse phase liquid chromatography–mass spectrometry (LC–MS) approach. We also determined if α-tocopherol status alters embryonic lipid peroxidation products by analyzing 24 different oxidized products of arachidonic or docosahexaenoic (DHA) acids in embryos using LC with hybrid quadrupole-time of flight MS. Adult zebrafish were fed E− or E+ diets for 4 months, and then were spawned to obtain E− and E+ embryos. Between 24 and 72 hours post-fertilization (hpf), arachidonic acid decreased 3-times faster in E− (21 pg/h) compared with E+ embryos (7 pg/h, P<0.0001), while both α-tocopherol and DHA concentrations decreased only in E− embryos. At 36 hpf, E− embryos contained double the 5-hydroxy-eicosatetraenoic acids and 7-hydroxy-DHA concentrations, while other hydroxy-lipids remained unchanged. Vitamin E deficiency during embryogenesis depleted DHA and arachidonic acid, and increased hydroxy-fatty acids derived from these PUFA, suggesting that α-tocopherol is necessary to protect these critical fatty acids. PMID:24416717

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.

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

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.

Relation of fatty acid composition in lead-exposed mallards to fat mobilization, lipid peroxidation and alkaline phosphatase activity

USGS Publications Warehouse

Mateo, R.; Beyer, W.N.; Spann, J.W.; Hoffman, D.J.

2003-01-01

The increase of n-6 polyunsaturated fatty acids (PUFA) in animal tissues has been proposed as a mechanism of lead (Pb) poisoning through lipid peroxidation or altered eicosanoids metabolism. We have studied fatty acid (FA) composition in liver and brain of mallards (Anas platyrhynchos) feeding for 3 weeks on diets containing combinations of low or high levels of vitamin E (20 or 200 UI/kg) and Pb (0 or 2 g/kg). Saturated FA, n-6 PUFA and total concentrations of FA were higher in livers of Pb-exposed mallards, but not in their brains. The percentage of n-6 PUFA in liver and brain was slightly higher in Pb-exposed mallards. The increase of n-6 PUFA in liver was associated with decreased triglycerides and increased cholesterol in plasma, thus could be in part attributed to feed refusal and fat mobilization. The hepatic ratios between adrenic acid (22:4 n-6) and arachidonic acid (20:4 n-6) or between adrenic acid and linoleic acid (18:2 n-6) were higher in Pb exposed birds, supporting the existing hypothesis of increased fatty acid elongation by Pb. Among the possible consequences of increased n-6 PUFA concentration in tissues, we found increased lipid peroxidation in liver without important histopathological changes, and decreased plasma alkaline phosphatase activity that may reflect altered bone metabolism in birds.

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.

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.

Development of a novel monoclonal antibody against 4-hydroxy-2E,6Z-dodecadienal (4-HDDE)-protein adducts: Immunochemical application in quantitative and qualitative analyses of lipid peroxidation in vitro and ex vivo.

PubMed

Uchida, Koji; Shibata, Takahiro; Toyokuni, Shinya; Daniel, Bareket; Zarkovic, Kamelija; Zarkovic, Neven; Sasson, Shlomo

2018-05-25

Non-enzymatic peroxidation of polyunsaturated fatty acids (PUFA) results in the formation of various α,β-unsaturated aldehydes, of which 4-hydroxyalkenals are abundant. The propensity of n-6 PUFA, such as linoleic acid, γ-linolenic acid and arachidonic acid, to undergo radical-induced peroxidation and generate 4-hydroxy-2E-nonenal (4-HNE) has been widely demonstrated. The ability of the latter to form covalent adducts with macromolecules and modify cellular functions has been linked to numerous pathological processes. Concomitantly, evidence has accumulated on specific signaling properties of low concentrations of 4-HNE that may induce hormetic and protective responses to peroxidation stress in cells. It has long been known that peroxidation of PUFA, and particularly arachidonic acid, also give rise to 4-hydroxy-2E,6Z-dodecadienal (4-HDDE), which is more chemically reactive than 4-HNE. Few studies on 4-HDDE revealed its ability to avidly interact covalently with electronegative moieties in macromolecules and to its ability to selectively activate the transcriptional regulator Peroxisome Proliferator-Activated Receptor (PPAR)-β/δ. The research on 4-HDDE has been impeded due to the lack of available pure 4-HDDE and antibodies that recognize 4-HDDE-modified epitopes in proteins. The purpose of this study was to employ an established procedure to synthesize 4-HDDE and use it to create and characterize a monoclonal antibody against 4-HDDE-modified proteins and establish its application for ELISA and immunohistochemical analysis of cells and tissues and further expand lipid peroxidation research. Copyright © 2018 Elsevier Inc. All rights reserved.

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

COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance.

PubMed

Poorani, R; Bhatt, Anant N; Dwarakanath, B S; Das, Undurti N

2016-08-15

Polyunsaturated fatty acids (PUFAs) are vital for normal growth and development and physiological function of various tissues in humans. PUFAs have immunomodulatory actions in addition to their ability to modulate inflammation, vascular reactivity, neurotransmission and stem cell biology. PUFAs and their metabolites possess both pro- and anti-inflammatory properties that underlie their actions and involvement in several diseases. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), possesses both cyclo-oxygenase (COX) and lipoxygenase (LOX) inhibitory action and enhances the production of anti-inflammatory lipoxin A4 {(called as epi-lipoxin A4, aspirin-triggered lipoxins (ATLs))}. In addition, at low doses aspirin may not interfere with the production of prostacyclin (PGI2). Both lipoxin A4 and PGI2 have vasodilator, platelet anti-aggregator and anti-inflammatory actions that may underlie the beneficial actions of aspirin. Paradoxically, other NSAIDs may not have the same actions as that of aspirin on PUFA metabolism. Similar anti-inflammatory compounds are formed from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by the action of aspirin termed as resolvins (from EPA and DHA) and protectins and maresins from DHA. PUFAs: arachidonic acid (AA), EPA and DHA and their various products modulate not only inflammation and immune response but also possess actions on various genes, nuclear factors, cyclic AMP and GMP, G-protein coupled receptors (GPRs), hypothalamic neurotransmitters, hormones, cytokines and enzymes, and interact with nitric oxide, carbon monoxide, and hydrogen sulfide to regulate their formation and action and to form new compounds that have several biological actions. These pleiotropic actions of PUFAs and their metabolites may explain their ability to play a role in several physiological actions and diseases. The big challenge is to harness these actions to prevent and manage clinical conditions. Copyright © 2015 Elsevier B.V. All

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.

Supplementation of arachidonic acid rich oil in European sea bass juveniles (Dicentrarchus labrax) diets: Effects on leucocytes and plasma fatty acid profiles, selected immune parameters and circulating prostaglandins levels.

PubMed

Torrecillas, S; Román, L; Rivero-Ramírez, F; Caballero, M J; Pascual, C; Robaina, L; Izquierdo, M S; Acosta, F; Montero, D

2017-05-01

The main objective of this study was to assess the effects of graded levels of dietary arachidonic acid (ARA), supplemented from alternative sources, on fatty acid composition of plasma and head kidney leucocytes of European sea bass (Dicentrarchus labrax). For that purpose, sea bass juveniles were fed four diets containing graded levels of ARA as follows: 0.5% (ARA0.5), 1% (ARA1), 2% (ARA2) and 4% (ARA4) during 60 days. At the end of the feeding trial fatty acid profiles of plasma and head kidney leucocytes were analyzed. Besides, plasma prostaglandins levels, head kidney leucocytes respiratory burst activity; peroxidase activity and phagocytic index were assayed. Reducing dietary ARA levels below 1% markedly reduced European sea bass growth performance. However, fish fed diet ARA0.5 tried to compensate this dietary ARA deficiency by a selective deposition of ARA on plasma and head kidney leucocytes, reaching similar levels to those fish fed diet ARA1 after 60 days of feeding. Nevertheless, head kidney phagocytic capacity was reduced as dietary ARA content in relation not only to variations on membrane composition but also to changes on fish basal prostaglandins levels. Results obtained demonstrated the importance to supply the necessary quantity n-6 LC-PUFA, and not only n-3 LC-PUFA levels, in European sea bass diets, in relation to not only growth performance but also immune system function. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population.

PubMed

Mathias, Rasika A; Vergara, Candelaria; Gao, Li; Rafaels, Nicholas; Hand, Tracey; Campbell, Monica; Bickel, Carol; Ivester, Priscilla; Sergeant, Susan; Barnes, Kathleen C; Chilton, Floyd H

2010-09-01

Long-chain polyunsaturated fatty acids (PUFA) orchestrate immunity and inflammation through their capacity to be converted to potent inflammatory mediators. We assessed associations of FADS gene cluster polymorphisms and fasting serum PUFA concentrations in a fully ascertained, geographically isolated founder population of European descent. Concentrations of 22 PUFAs were determined by gas chromatography, of which ten fatty acids and five ratios defining FADS1 and FADS2 activity were tested for genetic association against 16 single nucleotide polymorphisms (SNP) in 224 individuals. A cluster of SNPs in tight linkage disequilibrium in the FADS1 gene (rs174537, rs174545, rs174546, rs174553, rs174556, rs174561, rs174568, and rs99780) were strongly associated with arachidonic acid (AA) (P = 5.8 x 10(-7) - 1.7 x 10(-8)) among other PUFAs, but the strongest associations were with the ratio measuring FADS1 activity in the omega-6 series (P = 2.11 x 10(-13) - 1.8 x 10(-20)). The minor allele across all SNPs was consistently associated with decreased omega-6 PUFAs, with the exception of dihomo-gamma-linoleic acid (DHGLA), where the minor allele was consistently associated with increased levels. Our findings in a geographically isolated population with a homogenous dietary environment suggest that variants in the Delta-5 desaturase enzymatic step likely regulate the efficiency of conversion of medium-chain PUFAs to potentially inflammatory PUFAs, such as AA.

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...

Phosphate limitation promotes unsaturated fatty acids and arachidonic acid biosynthesis by microalgae Porphyridium purpureum.

PubMed

Su, Gaomin; Jiao, Kailin; Li, Zheng; Guo, Xiaoyi; Chang, Jingyu; Ndikubwimana, Theoneste; Sun, Yong; Zeng, Xianhai; Lu, Yinghua; Lin, Lu

2016-07-01

Polyunsaturated fatty acids (PUFAs) are highly appreciated on their nutritive value for human health and aquaculture. P. purpureum, one of the red microalgae acknowledged as a promising accumulator of ARA, was chosen as the target algae in the present research. Effects of sodium bicarbonate (0.04-1.2 g/L), temperature (25, 30 and 33 °C) and phosphate (0.00-0.14 g/L) on biomass yield, total fatty acids (TFA) and arachidonic acid (ARA) accumulation were investigated systemically. NaHCO3 dose of 0.8 g/L and moderate temperature of 30 °C were preferred. In addition, TFA and ARA production were significantly enhanced by an appropriate concentration of phosphate, and the highest TFA yield of 666.38 mg/L and ARA yield of 159.74 mg/L were obtained at a phosphate concentration of 0.035 g/L. Interestingly, with phosphate concentration continuing to fall, UFA/TFA and ARA/EPA ratios were increased accordingly, suggesting that phosphate limitation promoted unsaturated fatty acids and arachidonic acid biosynthesis. Low concentration of phosphate may be favored to increase the enzymatic activities of ∆6-desaturase, which played a key role in catalyzing the conversion of C16:0 to C18:2, and thus the selectivity of UFA increased. Meanwhile, the increase of ARA selectivity could be attributed to ω6 pathway promotion and ∆17-desaturase activity inhibition with phosphate limitation. Phosphate limitation strategy enhanced unsaturated fatty acids and ARA biosynthesis in P. purpureum, and can be applied in commercial scale manufacturing and commercialization of ARA.

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.

Long-chain polyunsaturated fatty acids and the preterm infant: a case study in developmentally sensitive nutrient needs in the United States.

PubMed

Brenna, J Thomas

2016-02-01

The vast majority of infant formulas in the United States contain the long-chain polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6), which were first permitted by the US Food and Drug Administration in 2001. As a scientific case study, preclinical animal studies of these nutrients definitively influenced the design and interpretation of human clinical studies. Early studies were tied to the availability of test substances, and in hindsight suggest re-evaluation of the essential fatty acid concept in light of the totality of available evidence. Research in the 1950s established the essentiality of n-6 PUFAs for skin integrity; however, widespread recognition of the essentiality of n-3 PUFAs came decades later despite compelling evidence of their significance. Barriers to an understanding of the essentiality of n-3 PUFAs were as follows: 1) their role is in neural function, which is measured only with difficulty compared with skin lesions and growth faltering that are apparent for n-6 PUFAs; 2) the experimental use of vegetable oils as PUFA sources that contain the inefficiently used C18 PUFAs rather than the operative C20 and C22 PUFAs; 3) the shift from reliance on high-quality animal studies to define mechanisms that established the required nutrients in the first part of the 20th century to inherently challenging human studies. Advances in nutrition of premature infants require the best practices and opinions available, taking into account the totality of preclinical and clinical evidence. © 2016 American Society for Nutrition.

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.

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

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 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

FADS genetic variants and ω-6 polyunsaturated fatty acid metabolism in a homogeneous island population[S

PubMed Central

Mathias, Rasika A.; Vergara, Candelaria; Gao, Li; Rafaels, Nicholas; Hand, Tracey; Campbell, Monica; Bickel, Carol; Ivester, Priscilla; Sergeant, Susan; Barnes, Kathleen C.; Chilton, Floyd H.

2010-01-01

Long-chain polyunsaturated fatty acids (PUFA) orchestrate immunity and inflammation through their capacity to be converted to potent inflammatory mediators. We assessed associations of FADS gene cluster polymorphisms and fasting serum PUFA concentrations in a fully ascertained, geographically isolated founder population of European descent. Concentrations of 22 PUFAs were determined by gas chromatography, of which ten fatty acids and five ratios defining FADS1 and FADS2 activity were tested for genetic association against 16 single nucleotide polymorphisms (SNP) in 224 individuals. A cluster of SNPs in tight linkage disequilibrium in the FADS1 gene (rs174537, rs174545, rs174546, rs174553, rs174556, rs174561, rs174568, and rs99780) were strongly associated with arachidonic acid (AA) (P = 5.8 × 10−7 – 1.7 × 10−8) among other PUFAs, but the strongest associations were with the ratio measuring FADS1 activity in the ω-6 series (P = 2.11 × 10−13 – 1.8 × 10−20). The minor allele across all SNPs was consistently associated with decreased ω-6 PUFAs, with the exception of dihomo-γ-linoleic acid (DHGLA), where the minor allele was consistently associated with increased levels. Our findings in a geographically isolated population with a homogenous dietary environment suggest that variants in the Δ-5 desaturase enzymatic step likely regulate the efficiency of conversion of medium-chain PUFAs to potentially inflammatory PUFAs, such as AA. PMID:20562440

Anti-inflammatory effects of omega 3 and omega 6 polyunsaturated fatty acids in cardiovascular disease and metabolic syndrome.

PubMed

Tortosa-Caparrós, Esther; Navas-Carrillo, Diana; Marín, Francisco; Orenes-Piñero, Esteban

2017-11-02

A lipid excess produces a systemic inflammation process due to tumor necrosis factor-α, interleukin-6 and C-reactive protein synthesis. Simultaneously, this fat excess promotes the appearance of insulin resistance. All this contributes to the development of atherosclerosis and increases the risk of cardiovascular diseases (CVDs). On the other hand, polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid and docosahexaenoic acid (omega 3), and arachidonic acid (omega 6) have shown anti-inflammatory properties. Lately, an inverse relationship between omega-3 fatty acids, inflammation, obesity and CVDs has been demonstrated. To check fatty acids effect, the levels of some inflammation biomarkers have been analyzed. Leptin, adiponectin and resistin represent a group of hormones associated with the development of CVDs, obesity, type 2 diabetes mellitus and insulin resistance and are modified in obese/overweight people comparing to normal weight people. Omega-3 PUFAs have been shown to decrease the production of inflammatory mediators, having a positive effect in obesity and diabetes mellitus type-2. Moreover, they significantly decrease the appearance of CVD risk factors. Regarding omega-6 PUFA, there is controversy whether their effects are pro- or anti-inflammatory. The aim of this manuscript is to provide a comprehensive overview about the role of omega-3 and omega-6 PUFAs in CVDs and metabolic syndrome.

Polyunsaturated Fatty Acids of Marine Macroalgae: Potential for Nutritional and Pharmaceutical Applications

PubMed Central

Pereira, Hugo; Barreira, Luísa; Figueiredo, Filipe; Custódio, Luísa; Vizetto-Duarte, Catarina; Polo, Cristina; Rešek, Eva; Engelen, Aschwin; Varela, João

2012-01-01

As mammals are unable to synthesize essential polyunsaturated fatty acids (PUFA), these compounds need to be taken in through diet. Nowadays, obtaining essential PUFA in diet is becoming increasingly difficult; therefore this work investigated the suitability of using macroalgae as novel dietary sources of PUFA. Hence, 17 macroalgal species from three different phyla (Chlorophyta, Phaeophyta and Rhodophyta) were analyzed and their fatty acid methyl esters (FAME) profile was assessed. Each phylum presented a characteristic fatty acid signature as evidenced by clustering of PUFA profiles of algae belonging to the same phylum in a Principal Components Analysis. The major PUFA detected in all phyla were C18 and C20, namely linoleic, arachidonic and eicosapentaenoic acids. The obtained data showed that rhodophytes and phaeophytes have higher concentrations of PUFA, particularly from the n-3 series, thereby being a better source of these compounds. Moreover, rhodophytes and phaeophytes presented “healthier” ∑n-6/∑n-3 and PUFA/saturated fatty acid ratios than chlorophytes. Ulva was an exception within the Chlorophyta, as it presented high concentrations of n-3 PUFA, α-linolenic acid in particular. In conclusion, macroalgae can be considered as a potential source for large-scale production of essential PUFA with wide applications in the nutraceutical and pharmacological industries. PMID:23118712

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

Menhaden oil, but not safflower or soybean oil, aids in restoring the polyunsaturated fatty acid profile in the novel delta-6-desaturase null mouse

PubMed Central

2012-01-01

Background Polyunsaturated fatty acids (PUFA) have diverse biological effects, from promoting inflammation to preventing cancer and heart disease. Growing evidence suggests that individual PUFA may have independent effects in health and disease. The individual roles of the two essential PUFA, linoleic acid (LA) and α-linolenic acid (ALA), have been difficult to discern from the actions of their highly unsaturated fatty acid (HUFA) downstream metabolites. This issue has recently been addressed through the development of the Δ-6 desaturase knock out (D6KO) mouse, which lacks the rate limiting Δ-6 desaturase enzyme and therefore cannot metabolize LA or ALA. However, a potential confounder in this model is the production of novel Δ-5 desaturase (D5D) derived fatty acids when D6KO mice are fed diets containing LA and ALA, but void of arachidonic acid. Objective The aim of the present study was to characterize how the D6KO model differentially responds to diets containing the essential n-6 and n-3 PUFA, and whether the direct provision of downstream HUFA can rescue the phenotype and prevent the production of D5D fatty acids. Methodology Liver and serum phospholipid (PL) fatty acid composition was examined in D6KO and wild type mice fed i) 10% safflower oil diet (SF, LA rich) ii) 10% soy diet (SO, LA+ALA) or iii) 3% menhaden oil +7% SF diet (MD, HUFA rich) for 28 days (n = 3-7/group). Results Novel D5D fatty acids were found in liver PL of D6KO fed SF or SO-fed mice, but differed in the type of D5D fatty acid depending on diet. Conversely, MD-fed D6KO mice had a liver PL fatty acid profile similar to wild-type mice. Conclusions Through careful consideration of the dietary fatty acid composition, and especially the HUFA content in order to prevent the synthesis of D5D fatty acids, the D6KO model has the potential to elucidate the independent biological and health effects of the parent n-6 and n-3 fatty acids, LA and ALA. PMID:22642787

Vibrational structure of the polyunsaturated fatty acids eicosapentaenoic acid and arachidonic acid studied by infrared spectroscopy

NASA Astrophysics Data System (ADS)

Kiefer, Johannes; Noack, Kristina; Bartelmess, Juergen; Walter, Christian; Dörnenburg, Heike; Leipertz, Alfred

2010-02-01

The spectroscopic discrimination of the two structurally similar polyunsaturated C 20 fatty acids (PUFAs) 5,8,11,14,17-eicosapentaenoic acid and 5,8,11,14-eicosatetraenoic acid (arachidonic acid) is shown. For this purpose their vibrational structures are studied by means of attenuated total reflection (ATR) Fourier-transform infrared (FT-IR) spectroscopy. The fingerprint regions of the recorded spectra are found to be almost identical, while the C-H stretching mode regions around 3000 cm -1 show such significant differences as results of electronic and molecular structure alterations based on the different degree of saturation that both fatty acids can be clearly distinguished from each other.

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.

The effects of arachidonic acid on the endocrine and osmoregulatory response of tilapia (Oreochromis mossambicus) acclimated to seawater and subjected to confinement stress.

PubMed

Van Anholt, R D; Spanings, F A T; Nixon, O; Wendelaar Bonga, S E; Koven, W M

2012-06-01

In previous studies in freshwater tilapia (Oreochromis mossambicus), dietary supplementation with arachidonic acid (ArA; 20:4n - 6) had considerable, opposing effects on the main ion-transporting enzyme Na(+)/K(+)-ATPase in gills and kidneys and changed the release of osmoregulatory hormones, such as cortisol. The present study was performed to assess the influence of dietary ArA on (1) the osmoregulatory capacity of tilapia acclimated to seawater (SW) (34‰) and (2) the osmoregulatory imbalance associated with acute stress. The increased ambient salinity was associated with significant alterations in the tissue fatty acid composition, particularly the n - 6 polyunsaturated fatty acids (PUFAs). Tissue levels of ArA were further increased as a result of dietary supplementation, whereas docosahexaenoic acid (DHA, 22:6n - 3) and eicosapentaenoic acid (EPA, 20:5n - 3) decreased in gills and kidneys. Basal plasma cortisol as well as lactate levels were elevated in the ArA-supplemented SW-acclimated tilapia compared with the control group. The 5 min of confinement (transient stress) increased plasma cortisol, glucose, and lactate levels with significantly higher levels in ArA-supplemented tilapia. Confinement was also associated with significantly elevated plasma osmolality, sodium, chloride, and potassium levels. ArA-supplemented tilapia showed markedly lower ionic disturbances after confinement, suggesting that dietary ArA can attenuate the hydromineral imbalance associated with acute stress. These results emphasize the involvement of ArA and/or its metabolites in the endocrine and osmoregulatory processes and the response to confinement stress.

Impact of Genetic and Epigenetic Variations Within the FADS Cluster on the Composition and Metabolism of Polyunsaturated Fatty Acids in Prostate Cancer.

PubMed

Cui, Tao; Hester, Austin G; Seeds, Michael C; Rahbar, Elaheh; Howard, Timothy D; Sergeant, Susan; Chilton, Floyd H

2016-09-01

In vitro and experimental animal studies have demonstrated that high levels of omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and high ratios of n-6 to omega-3 (n-3) PUFAs are strongly associated with the development and progression of prostate cancer (PCA). However, epidemiological studies in humans have demonstrated inconsistent findings linking dietary PUFAs and PCA risk. We hypothesize that genetic and epigenetic variations within the fatty acid desaturase (FADS) gene cluster produce gene-diet interactions that may explain these disparate findings. This study tested the relationship of the genotype of a single nucleotide polymorphism, rs174537, and the methylation status of a CpG site, cg27386326, with PUFA composition, and markers of PUFA biosynthesis in PCA tissue. Sixty PCA specimens from patients undergoing radical prostatectomy were genotyped, pyrosequenced and quantitated for fatty acids (FAs). Long-chain (LC)-PUFAs, such as arachidonic acid (ARA), were abundant in these specimens, with ARA accounting for 15.8% of total FAs. In addition, there was a positive association of the G allele at rs174537 with concentrations of ARA and adrenic acid and ratios of products to precursors within the n-6 PUFA pathway such that specimens from homozygous G individuals exhibited increasingly higher values as compared to specimens from heterozygous individuals and homozygous T individuals. Finally, the methylation status of cg27386326 was inversely correlated with tissue concentrations of LC-PUFAs and markers of LC-PUFA biosynthesis. These data reveal that genetic and epigenetic variations within the FADS cluster are highly associated with LC-PUFA concentrations and LC-PUFA biosynthetic capacity in PCA tissue. They also raise the potential that gene-PUFA interactions play an important role in PCA risk and severity. Prostate 76:1182-1191, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc. © 2016 The Authors. The Prostate published by Wiley

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.

Excessive ingestion of long-chain polyunsaturated fatty acids during developmental stage causes strain- and sex-dependent eye abnormalities in mice.

PubMed

Maekawa, Motoko; Iwayama, Yoshimi; Watanabe, Akiko; Nozaki, Yayoi; Ohnishi, Tetsuo; Ohba, Hisako; Toyoshima, Manabu; Hamazaki, Kei; Osumi, Noriko; Aruga, Jun; Yoshikawa, Takeo

2010-11-12

The eyes are rich in long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic acid [ARA; 20:4 (n-6)] and docosahexaenoic acid [DHA; 22:6 (n-3)]. Despite their abundance in the eyes, ARA and DHA cannot be sufficiently synthesized de novo in mammals. During gestation, eye development is exceptionally rapid, and substantial amounts of LC-PUFAs are needed to ensure proper eye development. Here, we studied the influences of dietary LC-PUFAs in dams (C57BL/6 and C3H/He) on the eye morphogenesis and organogenesis of their pups. Intriguingly, fetuses and newborn mice from C57BL/6 dams fed an LC-PUFA (particularly ARA)-enriched diet displayed a much higher incidence of eye abnormalities such as microphthalmia (small eye) and corneal opacity than those from dams fed an LC-PUFA-poor diet. The effects of LC-PUFAs on eye anomalies were evident only in the female pups of C57BL/6 inbred mice, not in those of C3H/He mice or male C57BL/6 mice. These results demonstrate a gene-by-environment (GxE) interaction in eye development in mice. Furthermore, our molecular analysis suggested the potential roles of Pitx3 and Pax6 in the above interaction involving ARA. Copyright © 2010 Elsevier Inc. All rights reserved.

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

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

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.

Cross-sectional associations of cortical β-amyloid with erythrocyte membrane long-chain polyunsaturated fatty acids in older adults with subjective memory complaints.

PubMed

Hooper, Claudie; De Souto Barreto, Philipe; Payoux, Pierre; Salabert, Anne Sophie; Guyonnet, Sophie; Andrieu, Sandrine; Vellas, Bruno

2017-08-01

Omega-3 (n-3) and 6 (n-6) polyunsaturated fatty acids (PUFAs) have been associated with reduced cognitive decline in observational studies. Hence, we examined the cross-sectional associations between cortical β-amyloid (Aβ) and erythrocyte membrane PUFAs in 61 non-demented elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial placebo arm. Cortical-to-cerebellar standard uptake value ratios were obtained using [ 18 F] florbetapir positron emission tomography. Fatty acids were measured in erythrocyte membranes by gas chromatography. Associations were explored using adjusted multiple linear regression models and were considered significant at p ≤ 0.005 after correction for multiple testing (10 comparisons). We found no significant associations between cortical Aβ and erythrocyte membrane PUFAs. The associations closest to significance after adjustment were those between Aβ and erythrocyte membrane arachidonic acid (without apolipoprotein E status adjustment: B-coefficient, 0.03; CI, 0.01, 0.05; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, 0.03; CI, 0.00, 0.06; p = 0.04) and Aβ and erythrocyte membrane linoleic acid (without apolipoprotein E status adjustment: B-coefficient, -0.02; CI, -0.04, 0.00; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, -0.02; CI, -0.04, 0.00; p = 0.09). Furthermore, the association between Aβ and erythrocyte membrane arachidonic acid seemed to be specific to Apolipoprotein E ε4 non-carriers (B-coefficient 0.03, CI: 0.00, 0.06, p = 0.03, n = 36). In contrast, no association was found between Aβ and erythrocyte membrane linoleic acid in Apolipoprotein E ε4 stratified analysis. Investigating the relationships between Aβ and PUFAs longitudinally would provide further evidence as to whether fatty acids, particularly arachidonic acid and linoleic acid, might modulate cognition through Aβ-dependent mechanisms. © 2017 International

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.

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

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.

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.

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

Systemic treatment with n-6 polyunsaturated fatty acids attenuates EL4 thymoma growth and metastasis through enhancing specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines.

PubMed

Salem, Mohamed Labib

2005-06-01

Recently, there has been a great interest in the effects of different types of n-6 polyunsaturated acids (n-6 PUFAs) upon the immune system and cancer development. However, the effects of n-6 PUFAs are still controversial and as yet undefined. The present study aimed to investigate the anti-tumor effects of n-6 PUFAs against EL4 thymoma and the associated immune mechanisms. To this, sesame oil, a vegetable oil enriched with n-6 PUFAs, or free linoleic acid (LA) were administered intraperitoneally into C57BL/6 mice before and after challenge with EL4 lymphoma cells. Treatment with either sesame oil or LA attenuated the growth and metastasis of EL4 lymphoma. The anti-tumor effect of LA was superior to that of sesame oil, and associated with an increase in the survival rate of the tumor-bearing mice. In addition, both sesame oil and LA showed dose-dependent anti-lymphoma growth in vitro. Treatment with LA generated significant increases in the anti-lymphoma cytolytic and cytostatic activities of T cells and macrophages, respectively, and enhanced production of IL-2 and IFN-gamma while decreased production of IL-4, IL-6 and IL-10. In summation, the results suggest that n-6 PUFAs, represented by LA, can attenuate EL4 lymphoma growth and metastasis through enhancing the specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines. These findings might be of great importance for a proper design of systemic nourishment with PUFAs emulsions for cancer patients.

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.

Dietary intake and plasma metabolomic analysis of polyunsaturated fatty acids in bipolar subjects reveal dysregulation of linoleic acid metabolism.

PubMed

Evans, Simon J; Ringrose, Rachel N; Harrington, Gloria J; Mancuso, Peter; Burant, Charles F; McInnis, Melvin G

2014-10-01

Polyunsaturated fatty acids (PUFA) profiles associate with risk for mood disorders. This poses the hypothesis of metabolic differences between patients and unaffected healthy controls that relate to the primary illness or are secondary to medication use or dietary intake. However, dietary manipulation or supplementation studies show equivocal results improving mental health outcomes. This study investigates dietary patterns and metabolic profiles relevant to PUFA metabolism, in bipolar I individuals compared to non-psychiatric controls. We collected seven-day diet records and performed metabolomic analysis of fasted plasma collected immediately after diet recording. Regression analyses adjusted for age, gender and energy intake found that bipolar individuals had significantly lower intake of selenium and PUFAs, including eicosapentaenoic acid (EPA) (n-3), docosahexaenoic acid (DHA) (n-3), arachidonic acid (AA) (n-6) and docosapentaenoic acid (DPA) (n-3/n-6 mix); and significantly increased intake of the saturated fats, eicosanoic and docosanoic acid. Regression analysis of metabolomic data derived from plasma samples, correcting for age, gender, BMI, psychiatric medication use and dietary PUFA intake, revealed that bipolar individuals had reduced 13S-HpODE, a major peroxidation product of the n-6, linoleic acid (LA), reduced eicosadienoic acid (EDA), an elongation product of LA; reduced prostaglandins G2, F2 alpha and E1, synthesized from n-6 PUFA; and reduced EPA. These observations remained significant or near significant after Bonferroni correction and are consistent with metabolic variances between bipolar and control individuals with regard to PUFA metabolism. These findings suggest that specific dietary interventions aimed towards correcting these metabolic disparities may impact health outcomes for individuals with bipolar disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

Polyunsaturated fatty acids ameliorate aging via redox-telomere-antioncogene axis.

PubMed

Chen, Jingnan; Wei, Yan; Chen, Xinyu; Jiao, Jingjing; Zhang, Yu

2017-01-31

Polyunsaturated fatty acids (PUFA), a group of nourishing and health-promoting nutrients, ameliorate age-related chronic diseases. However, how PUFA especially n-3 PUFA exert anti-aging functions remains poorly understood. Here we link fish oil, docosahexaenoic acid (DHA) and arachidonic acid (AA) to the aging etiology via a redox-telomere-antioncogene axis based on D-galactose-induced aging mice. Both fish oil and PUFA enhanced hepatic superoxide dismutase (SOD) and catalase activities and cardiac SOD activities within the range of 18%-46%, 26%-65% and 19%-58%, respectively, whereas reduced cerebral monoamine oxidase activity, plasma F2-isoprostane level and cerebral lipid peroxidation level by 56%-90%, 20%-79% and 16%-54%, respectively. Thus, PUFA improve the in vivo redox and oxidative stress induced aging process, which however does not exhibit a dose-dependent manner. Notably, both PUFA and fish oil effectively inactivated testicular telomerase and inhibited c-Myc-mediated telomerase reverse transcriptase expression, whereas n-3 PUFA rather than n-6 PUFA protected liver and testes against telomere shortening within the range of 13%-25% and 25%-27%, respectively. Therefore, n-3 PUFA may be better at inhibiting the DNA damage induced aging process. Surprisingly, only DHA significantly suppressed cellular senescence pathway evidenced by testicular antioncogene p16 and p53 expression. This work provides evident support for the crosstalk between PUFA especially n-3 PUFA and the aging process via maintaining the in vivo redox homeostasis, rescuing age-related telomere attrition and down-regulating the antioncogene expression.

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.

Genotype, production system and sex effects on fatty acid composition of meat from goat kids.

PubMed

Özcan, Mustafa; Demirel, Gulcan; Yakan, Akın; Ekiz, Bülent; Tölü, Cemil; Savaş, Türker

2015-02-01

Two trials were performed to assess the meat fatty acid profile of goat kids from different genotypes, production systems and sex. In the first trial, genotype effect was determined in 24 suckling male kids from Turkish Saanen, Maltese and Gokceada breeds. In the second trial, male and female Gokceada Goat kids were used to compare the effect of extensive and semi-intensive production systems on fatty acid composition of meat. Significant genotype effect was observed in the percentages of myristic acid (C14:0), palmitic acid (C16:0), oleic acid (C18:1 n-9), linolenic acid (C18:3 n-3), arachidonic acid (C20:4 n-6) and docosahexaenoic acid (C22:6 n-3), despite no differences on the ratios of polyunsaturated fatty acids to saturated fatty acids (PUFA/SFA) and n-6/n-3 (P > 0.05). The effect of production system had also significant effects on fatty acids, but sex only influenced significantly stearic acid (C18:0), C18:1 n-9 and C18:3 n-3 fatty acids and total PUFA level and PUFA/SFA ratio. This study confirms that dairy breeds are prone to produce higher levels of unsaturated fatty acids in their muscle. Meanwhile, meat from Gokceada goat kids, which is one of the indigenous breeds in Turkey, had similar PUFA/SFA and n-6/n-3 ratios to Turkish Saanen and Maltase. © 2014 Japanese Society of Animal Science.

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

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.

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.

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

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.

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.

Poxvirus-induced alteration of arachidonate metabolism.

PubMed Central

Palumbo, G J; Glasgow, W C; Buller, R M

1993-01-01

Recent evidence suggests that orthopoxviruses have an obligate requirement for arachidonic acid metabolites during replication in vivo and in vitro. Our report indicates that a virus family (Poxviridae) possesses multiple genes that function to regulate arachidonate metabolism. Analyses of BS-C-1 cells infected with cowpox virus or vaccinia virus detected enhanced arachidonate product formation from both the cyclooxygenase (specifically prostaglandins E2 and F2 alpha) and lipoxygenase (specifically 15-hydroxyeicosatetraenoic acid and 12-hydroxyeicosatetraenoic acid) pathways. In contrast, human parainfluenza type 3 or herpes simplex virus type 1 infections did not increase arachidonate metabolism. Results were consistent with a virus early-gene product either directly mediating or inducing a host factor that mediated the up-regulation of arachidonate metabolism, although vaccinia growth factor was not responsible. In addition, the cowpox virus 38-kDa protein-encoding gene, which is associated with inhibition of an inflammatory response, correlated with inhibition of formation of a product biochemically characteristic of (14R,15S)-dihydroxyeicosatetraenoic acid. We propose that orthopoxvirus-induced up-regulation of arachidonic acid metabolism during infection renders the infected cells susceptible to generation of inflammatory mediators from both the cyclooxygenase and the lipoxygenase pathways, and poxviruses, therefore, possess at least one gene (38K) that can alter the lipoxygenase-metabolite spectrum. PMID:8383332

Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies.

PubMed

Wu, Jason H Y; Marklund, Matti; Imamura, Fumiaki; Tintle, Nathan; Ardisson Korat, Andres V; de Goede, Janette; Zhou, Xia; Yang, Wei-Sin; de Oliveira Otto, Marcia C; Kröger, Janine; Qureshi, Waqas; Virtanen, Jyrki K; Bassett, Julie K; Frazier-Wood, Alexis C; Lankinen, Maria; Murphy, Rachel A; Rajaobelina, Kalina; Del Gobbo, Liana C; Forouhi, Nita G; Luben, Robert; Khaw, Kay-Tee; Wareham, Nick; Kalsbeek, Anya; Veenstra, Jenna; Luo, Juhua; Hu, Frank B; Lin, Hung-Ju; Siscovick, David S; Boeing, Heiner; Chen, Tzu-An; Steffen, Brian; Steffen, Lyn M; Hodge, Allison; Eriksdottir, Gudny; Smith, Albert V; Gudnason, Vilmunder; Harris, Tamara B; Brouwer, Ingeborg A; Berr, Claudine; Helmer, Catherine; Samieri, Cecilia; Laakso, Markku; Tsai, Michael Y; Giles, Graham G; Nurmi, Tarja; Wagenknecht, Lynne; Schulze, Matthias B; Lemaitre, Rozenn N; Chien, Kuo-Liong; Soedamah-Muthu, Sabita S; Geleijnse, Johanna M; Sun, Qi; Harris, William S; Lind, Lars; Ärnlöv, Johan; Riserus, Ulf; Micha, Renata; Mozaffarian, Dariush

2017-12-01

The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m 2 , who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I 2 =53·9%, p heterogeneity =0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid

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

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 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.

In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation

PubMed Central

Wang, Shu; Wu, Dayong; Lamon-Fava, Stefania; Matthan, Nirupa R.; Honda, Kaori L.; Lichtenstein, Alice H.

2010-01-01

Dietary long-chain PUFA, both n-3 and n-6, have unique benefits with respect to CVD risk. The aim of the present study was to determine the mechanisms by which n-3 PUFA (EPA, DHA) and n-6 PUFA (linoleic acid (LA), arachidonic acid (AA)) relative to SFA (myristic acid (MA), palmitic acid (PA)) alter markers of inflammation and cholesterol accumulation in macrophages (MΦ). Cells treated with AA and EPA elicited significantly less inflammatory response than control cells or those treated with MA, PA and LA, with intermediate effects for DHA, as indicated by lower levels of mRNA and secretion of TNFα, IL-6 and monocyte chemoattractant protein-1. Differences in cholesterol accumulation after exposure to minimally modified LDL were modest. AA and EPA resulted in significantly lower MΦ scavenger receptor 1 mRNA levels relative to control or MA-, PA-, LA- and DHA-treated cells, and ATP-binding cassette A1 mRNA levels relative to control or MA-, PA- and LA-treated cells. These data suggest changes in the rate of bidirectional cellular cholesterol flux. In summary, individual long-chain PUFA have differential effects on inflammatory response and markers of cholesterol flux in MΦ which are not related to the n position of the first double bond, chain length or degree of saturation. PMID:19660150

Baking reduces prostaglandin, resolvin, and hydroxy-fatty acid content of farm-raised Atlantic salmon (Salmo salar).

PubMed

Raatz, Susan K; Golovko, Mikhail Y; Brose, Stephen A; Rosenberger, Thad A; Burr, Gary S; Wolters, William R; Picklo, Matthew J

2011-10-26

The consumption of seafood enriched in n-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of cardiovascular disease. Several n-3 oxidation products from eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (22:6n-3) have known protective effects in the vasculature. It is not known whether the consumption of cooked seafood enriched in n-3 PUFA causes appreciable consumption of lipid oxidation products. We tested the hypothesis that baking Atlantic salmon (Salmo salar) increases the level of n-3 and n-6 PUFA oxidation products over raw salmon. We measured the contents of several monohydroxy-fatty acids (MHFA), prostanoids, and resolvins. Our data demonstrate that baking did not change the overall total levels of MHFA. However, baking resulted in selective regioisomeric loss of hydroxy fatty acids from arachidonic acid (20:4n-6) and EPA, while significantly increasing hydroxyl-linoleic acid levels. The contents of prostanoids and resolvins were reduced several-fold with baking. The inclusion of a coating on the salmon prior to baking reduced the loss of some MHFA but had no effect on prostanoid losses incurred by baking. Baking did not decrease n-3 PUFA contents, indicating that baking of salmon is an acceptable means of preparation that does not alter the potential health benefits of high n-3 seafood consumption. The extent to which the levels of MHFA, prostanoids, and resolvins in the raw or baked fish have physiologic consequence for humans needs to be determined.

The effects of season on fatty acid composition and ω3/ω6 ratios of northern pike ( Esox lucius L., 1758) muscle lipids

NASA Astrophysics Data System (ADS)

Mert, Ramazan; Bulut, Sait; Konuk, Muhsin

2015-01-01

In the present study, the effects of season on fatty acid composition, total lipids, and ω3/ω6 ratios of northern pike muscle lipids in Kizilirmak River (Kirikkale, Turkey) were investigated. A total of 35 different fatty acids were determined in gas chromatography. Among these, palmitic, oleic, and palmitoleic acids had the highest proportion. The main polyunsaturated fatty acids (PUFAs) were found to be docosahexaenoic acid, eicosapentaenoic acid, and arachidonic acid. There were more PUFAs than monounsaturated fatty acids (MUFA) in all seasons. Similarly, the percentages of ω3 fatty acids were higher than those of total ω6 fatty acids in the fatty acid composition. ω3/ω6 ratios were calculated as 1.53, 1.32, 1.97, and 1.71 in spring, summer, autumn and winter, respectively. Overall, we found that the fatty acid composition and ω3/ω6 fatty acid ratio in the muscle of northern pike were significantly influenced by season.

Low Plasma Eicosapentaenoic Acid Levels are Associated with Elevated Trait Aggression and Impulsivity in Major Depressive Disorder with a History of Comorbid Substance Use Disorder

PubMed Central

Beier, Anne Mette; Lauritzen, Lotte; Galfalvy, Hanga C.; Cooper, Thomas B.; Oquendo, Maria A.; Grunebaum, Michael F.; Mann, J. John; Sublette, M. Elizabeth

2014-01-01

Major depressive disorder (MDD) is associated with low levels of omega-3 polyunsaturated fatty acids (PUFAs), holding promise for new perspectives on disease etiology and treatment targets. As aggressive and impulsive behaviors are associated with low omega-3 PUFA levels in some clinical contexts, we investigated plasma PUFA relationships with trait aggression and impulsivity in patients with MDD. Medication-free MDD patients (n=48) and healthy volunteers (HV, n=35) were assessed with the Brown-Goodwin Aggression Inventory. A subset (MDD, n=39; HV, n=33) completed the Barratt Impulsiveness Scale. Plasma PUFAs eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6) were quantified and ln-transformed to mitigate distributional skew. Ln-transformed PUFA (lnPUFA) levels were predictors in regression models, with aggression or impulsivity scores as outcomes, and cofactors of sex and diagnostic status (MDD with or without a history of substance use disorder [SUD], or HV). Interactions were tested between relevant PUFAs and diagnostic status. Additional analyses explored possible confounds of depression severity, self-reported childhood abuse history, and, in MDD patients, suicide attempt history. Among PUFA, lnEPA but not lnDHA predicted aggression (F1,76=12.493, p=0.001), and impulsivity (F1,65=5.598, p=0.021), with interactions between lnEPA and history of SUD for both aggression (F1,76=7.941, p=0.001) and impulsivity (F1,65=3.485, p=0.037). Results remained significant when adjusted for childhood abuse, depression severity, or history of suicide attempt. In conclusion, low EPA levels were associated with aggression and impulsivity only in patients with MDD and comorbid SUD, even though in most cases SUD was in full sustained remission. PMID:25017608

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.

Regulation of vascular prostaglandin synthesis by metabolites of arachidonic acid in perfused rabbit aorta.

PubMed Central

Kent, R S; Diedrich, S L; Whorton, A R

1983-01-01

To address the hypothesis that metabolites of arachidonic acid are important regulators of prostaglandin (PG) synthesis in intact vascular tissue, we studied arachidonate metabolism in rabbit aortas in response to a continuous infusion of arachidonic acid, 10 micrograms/ml. Prostacyclin (PGI2; measured as 6-keto-PGF1 alpha) production rate accelerated during the first 2 min, reached peak velocity at 2 min, and then progressively decelerated. The velocity profile of PGI2 production was similar to that previously reported for cyclooxygenase holoenzyme assayed in vitro, and was consistent with progressive inactivation of the enzymes leading to PGI2 synthesis. We determined the specific inhibition of cyclooxygenase and prostacyclin synthetase by measuring PGI2 and PGE2 production rates and by infusing cyclic endoperoxides. Our results indicate preferential inactivation of cyclooxygenase during arachidonate metabolism, most likely due to cyclooxygenase-derived oxidative intermediates. This was a dose-dependent response and resulted in a progressive decrease in the 6-keto-PGF1 alpha/PGE2 ratio. Exogenously added 15-hydroperoxy eicosatetraenoic acid, on the other hand, actually stimulated cyclooxygenase activity at low doses, while markedly inhibiting prostacyclin synthetase. This finding, along with the accelerating nature of arachidonate metabolism, is consistent with the concept of "peroxide tone" as a mediator of cyclooxygenase activity in this system. These results demonstrate that arachidonate metabolites regulate PG synthesis in intact blood vessels. The progressive enzymatic inhibition intrinsic to arachidonate metabolism may be a model for similar changes occurring in states of enhanced lipid peroxidation. These metabolic alterations might greatly influence the numerous vascular functions known to involve arachidonic acid metabolism. PMID:6409932

Comparison of longissimus dorsi Fatty Acids Profiles in Gansu Black Yak and Chinese Yellow Cattle Steers and Heifers.

PubMed

Zhang, S G; Liu, T; Brown, M A; Wu, J P

2015-01-01

Fatty acid (FA) composition of longissimus dorsi intramuscular fat in Black Yak and Chinese Yellow Cattle were evaluated in 44 Black Yak and 41 Chinese Yellow Cattle of both genders. Interactions of species with gender were observed for total saturated fatty acid (SFA), unsaturated fatty acid (UFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), palmitic acid, stearic acid, oleic acid, linolenic acid, arachidonic acid, EPA, and DHA concentrations, as well as PUFA/SFA ratio in the longissimus dorsi (p<0.05). The SFA percentage was greater in yellow cattle than yak in both genders but the species difference in heifers was greater than in steers (p<0.05). Yak had greater UFA, MUFA and PUFA percentages than yellow cattle in both steers and heifers (p<0.05) but the difference between yak and yellow cattle heifers was greater than yak and yellow cattle steers. The percentages of inolenic acid, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid; and PUFA/SFA were greater in yak than yellow cattle in both steers and heifers (p<0.05). In addition, the ratio of n-6/n-3 PUFA in yak was lesser than in yellow cattle (p<0.05). These results indicated that FA composition generally differed between yak and yellow cattle but the differences were not the same in heifers as compared to steers. Results also suggested that species differences in FA composition tended to favor Black Yak over Chinese Yellow Cattle, indicating that the longissimus dorsi of Black Yak may have a higher nutritive value than that of Chinese Yellow Cattle and potential for development as a desirable natural product.

Comparison of longissimus dorsi Fatty Acids Profiles in Gansu Black Yak and Chinese Yellow Cattle Steers and Heifers

PubMed Central

Zhang, S. G.; Liu, T.; Brown, M. A.; Wu, J. P.

2015-01-01

Fatty acid (FA) composition of longissimus dorsi intramuscular fat in Black Yak and Chinese Yellow Cattle were evaluated in 44 Black Yak and 41 Chinese Yellow Cattle of both genders. Interactions of species with gender were observed for total saturated fatty acid (SFA), unsaturated fatty acid (UFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), palmitic acid, stearic acid, oleic acid, linolenic acid, arachidonic acid, EPA, and DHA concentrations, as well as PUFA/SFA ratio in the longissimus dorsi (p<0.05). The SFA percentage was greater in yellow cattle than yak in both genders but the species difference in heifers was greater than in steers (p<0.05). Yak had greater UFA, MUFA and PUFA percentages than yellow cattle in both steers and heifers (p<0.05) but the difference between yak and yellow cattle heifers was greater than yak and yellow cattle steers. The percentages of inolenic acid, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid; and PUFA/SFA were greater in yak than yellow cattle in both steers and heifers (p<0.05). In addition, the ratio of n-6/n-3 PUFA in yak was lesser than in yellow cattle (p<0.05). These results indicated that FA composition generally differed between yak and yellow cattle but the differences were not the same in heifers as compared to steers. Results also suggested that species differences in FA composition tended to favor Black Yak over Chinese Yellow Cattle, indicating that the longissimus dorsi of Black Yak may have a higher nutritive value than that of Chinese Yellow Cattle and potential for development as a desirable natural product. PMID:26761841

Reduction of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring body composition: follow-up results from a randomized controlled trial up to 5 y of age.

PubMed

Brei, Christina; Stecher, Lynne; Much, Daniela; Karla, Marie-Theres; Amann-Gassner, Ulrike; Shen, Jun; Ganter, Carl; Karampinos, Dimitrios C; Brunner, Stefanie; Hauner, Hans

2016-06-01

It has been hypothesized that the n-6:n-3 (ω-6:ω-3) long-chain polyunsaturated fatty acid (LCPUFA) ratio in the maternal diet during the prenatal and early postnatal phase positively affects the body composition of the offspring. However, only limited data from prospective human intervention studies with long-term follow-up are available. We assessed the long-term effects of a reduced n-6:n-3 LCPUFA ratio in the diets of pregnant and lactating women [1020 mg docosahexaenoic acid (DHA) plus 180 mg eicosapentaenoic acid (EPA)/d together with an arachidonic acid-balanced diet compared with a control diet] on the body weights and compositions of their offspring from 2 to 5 y of age with a focus on the 5-y results. Participants in the randomized controlled trial received follow-up assessments with annual body-composition measurements including skinfold thickness (SFT) measurements (primary outcome), a sonographic assessment of abdominal subcutaneous and preperitoneal fat, and child growth. In addition, abdominal MRI was performed in a subgroup of 5-y-old children. For the statistical analysis, mixed models for repeated measures (MMRMs) were fit with the use of data from each visit since birth (except for MRI). Maternal LCPUFA supplementation did not significantly influence the children's sum of 4 SFTs [means ± SDs at 5 y of age: intervention, 23.9 ± 4.7 mm (n = 57); control, 24.5 ± 5.0 mm (n = 55); adjusted mean difference, -0.5 (95% CI: -2.2, 1.2)], growth, or ultrasonography measures at any time point in the adjusted MMRM model (all P values < 0.05). Results were consistent with abdominal MRI measurements (n = 44) at 5 y of age, which showed no significant differences in subcutaneous and visceral adipose tissue volumes and ratios. The current study provides no evidence that a dietary reduction of the n-6:n-3 LCPUFA ratio in the maternal diet during pregnancy and lactation is a useful early preventive strategy against obesity at preschool age. This trial was

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.

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

Dietary n-6 and n-3 fatty acids in immunity and autoimmune disease.

PubMed

Harbige, L S

1998-11-01

Clearly there is much evidence to show that under well-controlled laboratory and dietary conditions fatty acid intake can have profound effects on animal models of autoimmune disease. Studies in human autoimmune disease have been less dramatic; however, human trials have been subject to uncontrolled dietary and genetic backgrounds, infection and other environmental influences, and basic trial designs have been inadequate. The impact of dietary fatty acids on animal autoimmune disease models appears to depend on the animal model and the type and amount of fatty acids fed. Diets low in fat, essential fatty acid-deficient, or high in n-3 fatty acids from fish oils increase the survival and reduce disease severity in spontaneous autoantibody-mediated disease, whilst linoleic acid-rich diets appear to increase disease severity. In experimentally-induced T-cell-mediated autoimmune disease, essential fatty acid-deficient diets or diets supplemented with n-3 fatty acids appear to augment disease, whereas n-6 fatty acids prevent or reduce the severity. In contrast, in both T-cell and antibody-mediated auto-immune disease the desaturated and elongated metabolites of linoleic acid are protective. Suppression of autoantibody and T lymphocyte proliferation, apoptosis of autoreactive lymphocytes, and reduced pro-inflammatory cytokine production by high-dose fish oils are all likely mechanisms by which n-3 fatty acids ameliorate autoimmune disease. However, these could be undesirable long-term effects of high-dose fish oil which may compromise host immunity. The protective mechanism(s) of n-6 fatty acids in T-cell- mediated autoimmune disease are less clear, but may include dihomo-gamma-linolenic acid- and arachidonic acid-sensitive immunoregulatory circuits such as Th1 responses, TGF beta 1-mediated effects and Th3-like responses. It is often claimed that n-6 fatty acids promote autoimmune and inflammatory disease based on results obtained with linoleic acid only. It should be

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.

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

Baking Reduces Prostaglandin, Resolvin, and Hydroxy-Fatty Acid Content of Farm-Raised Atlantic Salmon (Salmo salar)

PubMed Central

Raatz, Susan K.; Golovko, Mikhail Y.; Brose, Stephen A.; Rosenberger, Thad A.; Burr, Gary S.; Wolters, William R.; Picklo, Matthew J.

2011-01-01

Consumption of seafood enriched in n-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of cardiovascular disease. Several n-3 oxidation products from eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) have known protective effects in the vasculature. It is not known whether consumption of cooked seafood enriched in n-3 PUFA causes appreciable consumption of lipid oxidation products. We tested the hypothesis that baking Atlantic salmon (Salmo salar) increases the level of n-3 and n-6 PUFA oxidation products over raw salmon. We measured the content of several monohydroxy-fatty acids (MHFA), prostanoids, and resolvins. Our data demonstrate that baking did not change the overall total levels of MHFA. However, baking resulted in selective regio-isomeric loss of hydroxy fatty acids from arachidonic acid (20:4n-6), and EPA while significantly increasing hydroxyl-linoleic acid levels. The content of prostanoids and resolvins were reduced several-fold with baking. The inclusion of coating upon the salmon prior to baking reduced the loss of some MHFA but had no effect upon prostanoid losses incurred by baking. Baking did not decrease n-3 PUFA content indicating that baking of salmon is an acceptable means of preparation that does not alter the potential health benefits of high n-3 seafood consumption. The extent to which the levels of MHFA, prostanoids and resolvins in the raw or baked fish have physiologic consequence for humans needs to be determined. PMID:21919483

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.

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.

Gene Expression of Desaturase (FADS1 and FADS2) and Elongase (ELOVL5) Enzymes in Peripheral Blood: Association with Polyunsaturated Fatty Acid Levels and Atopic Eczema in 4-Year-Old Children

PubMed Central

Chisaguano, Aida Maribel; Montes, Rosa; Pérez-Berezo, Teresa; Castellote, Ana Isabel; Guerendiain, Marcela; Bustamante, Mariona; Morales, Eva; García-Esteban, Raquel; Sunyer, Jordi; Franch, Àngels; López-Sabater, M. Carmen

2013-01-01

Abstract Background It is unknown if changes in the gene expression of the desaturase and elongase enzymes are associated with abnormal n-6 long chain polyunsaturated fatty acid (LC-PUFA) levels in children with atopic eczema (AE). We analyzed whether mRNA-expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children. Methods AE (n=20) and non-AE (n=104) children participating in the Sabadell cohort within the INfancia y Medio Ambiente (INMA) Project were included in the present study. RT-PCR with TaqMan Low-Density Array cards was used to measure the mRNA-expression of FADS1, FADS2 and ELOVL5. LC-PUFA levels were measured by fast gas chromatography in plasma phospholipids. The relationship of gene expression with LC-PUFA levels and enzyme activities was evaluated by Pearson’s rank correlation coefficient, and logistic regression models were used to study its association with risk of developing AE. Results Children with AE had lower levels of several n-6 PUFA members, dihomo-γ-linolenic (DGLA) and arachidonic (AA) acids. mRNA-expression levels of FADS1 and 2 strongly correlated with DGLA levels and with D6D activity. FADS2 and ELOVL5 mRNA-expression levels were significantly lower in AE than in non-AE children (-40.30% and -20.36%; respectively), but no differences were found for FADS1. Conclusions and Significance Changes in the mRNA-expression levels of FADS1 and 2 directly affect blood DGLA levels and D6D activity. This study suggests that lower mRNA-expressions of FADS2 and ELOVL5 are associated with higher risk of atopic eczema in young children. PMID:24167612

Gene expression of desaturase (FADS1 and FADS2) and Elongase (ELOVL5) enzymes in peripheral blood: association with polyunsaturated fatty acid levels and atopic eczema in 4-year-old children.

PubMed

Chisaguano, Aida Maribel; Montes, Rosa; Pérez-Berezo, Teresa; Castellote, Ana Isabel; Guerendiain, Marcela; Bustamante, Mariona; Morales, Eva; García-Esteban, Raquel; Sunyer, Jordi; Franch, Angels; López-Sabater, M Carmen

2013-01-01

It is unknown if changes in the gene expression of the desaturase and elongase enzymes are associated with abnormal n-6 long chain polyunsaturated fatty acid (LC-PUFA) levels in children with atopic eczema (AE). We analyzed whether mRNA-expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children. AE (n=20) and non-AE (n=104) children participating in the Sabadell cohort within the INfancia y Medio Ambiente (INMA) Project were included in the present study. RT-PCR with TaqMan Low-Density Array cards was used to measure the mRNA-expression of FADS1, FADS2 and ELOVL5. LC-PUFA levels were measured by fast gas chromatography in plasma phospholipids. The relationship of gene expression with LC-PUFA levels and enzyme activities was evaluated by Pearson's rank correlation coefficient, and logistic regression models were used to study its association with risk of developing AE. Children with AE had lower levels of several n-6 PUFA members, dihomo-γ-linolenic (DGLA) and arachidonic (AA) acids. mRNA-expression levels of FADS1 and 2 strongly correlated with DGLA levels and with D6D activity. FADS2 and ELOVL5 mRNA-expression levels were significantly lower in AE than in non-AE children (-40.30% and -20.36%; respectively), but no differences were found for FADS1. Changes in the mRNA-expression levels of FADS1 and 2 directly affect blood DGLA levels and D6D activity. This study suggests that lower mRNA-expressions of FADS2 and ELOVL5 are associated with higher risk of atopic eczema in young children.

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.

Salmon diet in patients with active ulcerative colitis reduced the simple clinical colitis activity index and increased the anti-inflammatory fatty acid index--a pilot study.

PubMed

Grimstad, Tore; Berge, Rolf K; Bohov, Pavol; Skorve, Jon; Gøransson, Lasse; Omdal, Roald; Aasprong, Ole G; Haugen, Margaretha; Meltzer, Helle M; Hausken, Trygve

2011-02-01

Data concerning the anti-inflammatory effect of dietary n-3 polyunsaturated fatty acids (PUFAs) in patients with ulcerative colitis (UC) are inconsistent. Salmon fillet contains n-3 PUFAs and bioactive peptides that may improve its effects compared to fish oil alone. We assessed the efficacy of a salmon-rich diet in patients with mild ulcerative colitis. An 8-week intervention pilot study was designed to assess the effects of 600 grams Atlantic salmon consumption weekly in 12 UC patients. Simple clinical colitis activity index (SCCAI), a dietary questionnaire, sigmoidoscopy, selected serum inflammatory markers, fecal calprotectin, and plasma and rectal biopsy fatty acid profiles were assessed before and after intervention. The levels of C20:4n-6 arachidonic acid in biopsies after dietary intervention were correlated with histology and endoscopy scores. The concentrations of n-3 PUFAs, C20:5n-3 eicosapentaenoic acid, C22:6n-3 docosahexaenoic acid, and the n-3/n-6 ratio increased in plasma and rectal biopsies. The anti-inflammatory fatty acid index (AIFAI) increased both in biopsies and plasma accompanied with a significantly reduced SCCAI. Based on evidence of SCCAI and AIFAI and a tendency of decreased levels of CRP and homocysteine, intake of Atlantic salmon may have beneficial effects on disease activity in patients with mild ulcerative colitis.

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

Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature.

PubMed

Norambuena, Fernando; Morais, Sofia; Emery, James A; Turchini, Giovanni M

2015-01-01

Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad-time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature

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.

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.

Low plasma eicosapentaenoic acid levels are associated with elevated trait aggression and impulsivity in major depressive disorder with a history of comorbid substance use disorder.

PubMed

Beier, Anne Mette; Lauritzen, Lotte; Galfalvy, Hanga C; Cooper, Thomas B; Oquendo, Maria A; Grunebaum, Michael F; Mann, J John; Sublette, M Elizabeth

2014-10-01

Major depressive disorder (MDD) is associated with low levels of omega-3 polyunsaturated fatty acids (PUFAs), holding promise for new perspectives on disease etiology and treatment targets. As aggressive and impulsive behaviors are associated with low omega-3 PUFA levels in some clinical contexts, we investigated plasma PUFA relationships with trait aggression and impulsivity in patients with MDD. Medication-free MDD patients (n = 48) and healthy volunteers (HV, n = 35) were assessed with the Brown-Goodwin Aggression Inventory. A subset (MDD, n = 39; HV, n = 33) completed the Barratt Impulsiveness Scale. Plasma PUFAs eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6) were quantified and ln-transformed to mitigate distributional skew. Ln-transformed PUFA (lnPUFA) levels were predictors in regression models, with aggression or impulsivity scores as outcomes, and cofactors of sex and diagnostic status (MDD with or without a history of substance use disorder [SUD], or HV). Interactions were tested between relevant PUFAs and diagnostic status. Additional analyses explored possible confounds of depression severity, self-reported childhood abuse history, and, in MDD patients, suicide attempt history. Among PUFA, lnEPA but not lnDHA predicted aggression (F1,76 = 12.493, p = 0.001), and impulsivity (F1,65 = 5.598, p = 0.021), with interactions between lnEPA and history of SUD for both aggression (F1,76 = 7.941, p = 0.001) and impulsivity (F1,65 = 3.485, p = 0.037). Results remained significant when adjusted for childhood abuse, depression severity, or history of suicide attempt. In conclusion, low EPA levels were associated with aggression and impulsivity only in patients with MDD and comorbid SUD, even though in most cases SUD was in full sustained remission. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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.

Eicosapentaenoic acid membrane incorporation impairs ABCA1-dependent cholesterol efflux via a protein kinase A signaling pathway in primary human macrophages.

PubMed

Fournier, Natalie; Tardivel, Sylviane; Benoist, Jean-François; Vedie, Benoît; Rousseau-Ralliard, Delphine; Nowak, Maxime; Allaoui, Fatima; Paul, Jean-Louis

2016-04-01

A diet rich in n-3/n-6 polyunsaturated fatty acids (PUFAs) is cardioprotective. Dietary PUFAs affect the cellular phospholipids composition, which may influence the function of membrane proteins. We investigated the impact of the membrane incorporation of several PUFAs on ABCA1-mediated cholesterol efflux, a key antiatherogenic pathway. Arachidonic acid (AA) (C20:4 n-6) and docosahexaenoic acid (DHA) (C22:6 n-3) decreased or increased cholesterol efflux from J774 mouse macrophages, respectively, whereas they had no effect on efflux from human monocyte-derived macrophages (HMDM). Importantly, eicosapentaenoic acid (EPA) (C20:5 n-3) induced a dose-dependent reduction of ABCA1 functionality in both cellular models (-28% for 70μM of EPA in HMDM), without any alterations in ABCA1 expression. These results show that PUFA membrane incorporation does not have the same consequences on cholesterol efflux from mouse and human macrophages. The EPA-treated HMDM exhibited strong phospholipid composition changes, with high levels of both EPA and its elongation product docosapentaenoic acid (DPA) (C22:5 n-3), which is associated with a decreased level of AA. In HMDM, EPA reduced the ATPase activity of the membrane transporter. Moreover, the activation of adenylate cyclase by forskolin and the inhibition of cAMP phosphodiesterase by isobutylmethylxanthine restored ABCA1 cholesterol efflux in EPA-treated human macrophages. In conclusion, EPA membrane incorporation reduces ABCA1 functionality in mouse macrophages as well as in primary human macrophages and this effect seems to be PKA-dependent in human macrophages. Copyright © 2016 Elsevier B.V. All rights reserved.

AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonyl-meth oxy coumarin) inhibits the release of arachidonic acid in human platelets stimulated by thrombin

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

Porcellati, S.; Costantini, V.; Prosdocimi, M.

1987-07-01

The coumarin derivative AD6 is known to inhibit platelet aggregation and release and it possesses vasodilatory properties on coronary arteries of laboratory animals. Furthermore, the inhibition of the production of TxB2 from endogenous substrates after stimulation of human platelets with collagen has been demonstrated. The present report demonstrates that AD6 inhibits the production of labeled arachidonic acid and diglycerides from phospholipids of platelets stimulated with thrombin. This effect is dose-dependent and is already evident at a concentration of the drug (25 microM) which is unable to prevent the aggregation. Apparently, AD6 inhibits the release of arachidonic acid from phosphatidylinositol andmore » choline phosphoglycerides which are the main sources of the substrate for the synthesis of prostaglandins and thromboxanes.« less

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

The effect of replacing saturated fat with mostly n-6 polyunsaturated fat on coronary heart disease: a meta-analysis of randomised controlled trials.

PubMed

Hamley, Steven

2017-05-19

A cornerstone of conventional dietary advice is the recommendation to replace saturated fatty acids (SFA) with mostly n-6 polyunsaturated fatty acids (PUFA) to reduce the risk of coronary heart disease (CHD). Many clinical trials aimed to test this advice and have had their results pooled in several meta-analyses. However, earlier meta-analyses did not sufficiently account for major confounding variables that were present in some of those trials. Therefore, the aim of the study was to account for the major confounding variables in the diet heart trials, and emphasise the results from those trials that most accurately test the effect of replacing SFA with mostly n-6 PUFA. Clinical trials were identified from earlier meta-analyses. Relevant trials were categorised as 'adequately controlled' or 'inadequately controlled' depending on whether there were substantial dietary or non-dietary differences between the experimental and control groups that were not related to SFA or mostly n-6 PUFA intake, then were subject to different subgroup analyses. When pooling results from only the adequately controlled trials there was no effect for major CHD events (RR = 1.06, CI = 0.86-1.31), total CHD events (RR = 1.02, CI = 0.84-1.23), CHD mortality (RR = 1.13, CI = 0.91-1.40) and total mortality (RR = 1.07, CI = 0.90-1.26). Whereas, the pooled results from all trials, including the inadequately controlled trials, suggested that replacing SFA with mostly n-6 PUFA would significantly reduce the risk of total CHD events (RR = 0.80, CI = 0.65-0.98, P = 0.03), but not major CHD events (RR = 0.87, CI = 0.70-1.07), CHD mortality (RR = 0.90, CI = 0.70-1.17) and total mortality (RR = 1.00, CI = 0.90-1.10). Available evidence from adequately controlled randomised controlled trials suggest replacing SFA with mostly n-6 PUFA is unlikely to reduce CHD events, CHD mortality or total mortality. The suggestion of benefits reported

Arachidonic acid metabolites in normal and autoimmune mice do not influence lymphocyte-high endothelial venule interactions.

PubMed

Manolios, N; Bakiera, B; Geczy, C L; Schrieber, L

1991-02-01

In peripheral lymphoid organs the number of lymphocytes and the proportion of functional lymphocyte subsets are regulated by multiple factors including the control of lymphocyte migration by selective lymphocyte-high endothelial venule (HEV) interactions. In this study, prostaglandin E2 (PGE2) levels from normal and autoimmune mouse lymph node cells were measured. The contribution of eicosanoids to lymphocyte-HEV interactions in normal (CBA/T6) and autoimmune (MRL/n) mice was examined. There was no association between PGE2 production in normal or autoimmune mice and the age of onset of disease activity in the latter strains. Arachidonic acid metabolites, in particular PGE2 and leukotriene B4 (LTB4), did not have any effects on lymphocyte-HEV binding. Likewise, lymphocytes treated in vivo and/or in vitro with arachidonic acid metabolite inhibitors (acetyl salicylic acid, indomethacin, BW755C) did not alter lymphocyte-HEV binding interactions in both normal and autoimmune mice. No clinical significance could be attributed to lymph node PGE2 production and the age of onset of autoimmune disease. In summary, these findings cast doubt on the role of arachidonic acid metabolites in lymphocyte-HEV binding interactions.

Combining eicosapentaenoic acid, decosahexaenoic acid and arachidonic acid, using a fully crossed design, affect gene expression and eicosanoid secretion in salmon head kidney cells in vitro.

PubMed

Holen, Elisabeth; He, Juyun; Espe, Marit; Chen, Liqiou; Araujo, Pedro

2015-08-01

Future feed for farmed fish are based on untraditional feed ingredients, which will change nutrient profiles compared to traditional feed based on marine ingredients. To understand the impact of oils from different sources on fish health, n-6 and n-3 polyunsaturated fatty acids (PUFAs) were added to salmon head kidney cells, in a fully crossed design, to monitor their individual and combined effects on gene expression. Exposing salmon head kidney cells to single fatty acids, arachidonic acid (AA) or decosahexaenoic acid (DHA), resulted in down-regulation of cell signaling pathway genes and specific fatty acid metabolism genes as well as reduced prostaglandin E2 (PGE2) secretion. Eicosapentaenoic acid (EPA) had no impact on gene transcription in this study, but reduced the cell secretion of PGE2. The combined effect of AA + EPA resulted in up-regulation of eicosanoid pathway genes and the pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α), Bclx (an inducer of apoptosis) and fatty acid translocase (CD36) as well as increased cell secretion of PGE2 into the media. Adding single fatty acids to salmon head kidney cells decreased inflammation markers in this model. The combination AA + EPA acted differently than the rest of the fatty acid combinations by increasing the inflammation markers in these cells. The concentration of fatty acid used in this experiment did not induce any lipid peroxidation responses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison between omega-3 and omega-6 polyunsaturated fatty acid intakes as assessed by a food frequency questionnaire and erythrocyte membrane fatty acid composition in young children

PubMed Central

Orton, Heather D.; Szabo, Nancy J.; Clare-Salzler, Michael; Norris, Jill M.

2010-01-01

Objective We conducted a dietary validation study in youth aged 1 to 11 years by comparing dietary intake of omega-3 and omega-6 polyunsaturated fatty acids (PUFA) as assessed by a parent-completed semi-quantitative food frequency questionnaire (FFQ) over time to erythrocyte membrane composition of the same fatty acids. Design The study population included youth aged 1 to 11 years who were participants in the Diabetes Autoimmunity Study in the Young (DAISY), a longitudinal study in Denver, Colorado that is following a cohort of youth at risk for developing Type I diabetes. Four hundred four children who had erythrocyte membrane fatty acid data matched to an FFQ corresponding to the same time frame for a total of 917 visits (matches) were included. PUFA intake was expressed as both g/day (adjusted for total energy) and as percent of total fat intake. We used mixed models to test the association and calculate the correlation between the erythrocyte membrane estimates and PUFA intake using all records of data for each youth. Results Intakes of total omega-3 fatty acids (β=0.52, p<0.0001, ρ=0.23) and marine PUFAs (β=1.62, p<0.0001, ρ=0.42), as a percent of total fat in the diet, were associated with percent of omega-3 and marine PUFAs in the erythrocyte membrane. Intakes of omega-6 PUFAs (β=0.04, p=0.418, ρ=0.05) and arachidonic acid (β=0.31, p=0.774, ρ=0.01) were not associated. Conclusions In these young children, a FFQ using parental report provided estimates of average long-term intakes of marine PUFAs that correlated well with their erythrocyte cell membrane fatty acid status. PMID:17440518

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

Dried blood spot omega-3 and omega-6 long chain polyunsaturated fatty acid levels in 7-9 year old Zimbabwean children: a cross sectional study.

PubMed

Mashavave, Grace; Kuona, Patience; Tinago, Willard; Stray-Pedersen, Babill; Munjoma, Marshall; Musarurwa, Cuthbert

2016-01-01

Omega-3 long chain-polyunsaturated fatty acids (LC-PUFAs)-docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and eicosapentaenoic acid (EPA)- and omega-6 LC-PUFA arachidonic acid (ARA), are essential for optimum physical and mental development in children. Prior to this study, the blood omega-3 LC-PUFA levels were unknown in Zimbabwean children, particularly in those aged 7-9 years, despite the documented benefits of LC-PUFAs. Documentation of the LC-PUFA levels in this age group would help determine whether interventions, such as fortification, are necessary. This study aimed to determine dried whole blood spot omega-3 and omega-6 LC-PUFA levels and LC-PUFA reference intervals among a selected group of Zimbabwean children aged 7-9 years old. We conducted a cross sectional study from September 2011 to August 2012 on a cohort of peri-urban, Zimbabwean children aged 7-9 years. The children were born to mothers enrolled at late pregnancy into an HIV prevention program between 2002 and 2004. Dried whole blood spots were sampled on butylated hydroxytoluene antioxidant impregnated filter papers and dried. LC-PUFAs were quantified using gas liquid chromatography. Differences in LC-PUFAs between groups were compared using the Kruskal Wallis test and reference intervals determined using non-parametric statistical methods. LC-PUFAs levels were determined in 297 Zimbabwean children of whom 170 (57.2 %) were girls. The study determined that LC-PUFAs (wt/wt) ranges were EPA 0.06-0.55 %, DPA 0.38-1.98 %, DHA 1.13-3.52 %, ARA 5.58-14.64 % and ARA: EPA ratio 15.47-1633.33. Sixteen participants had omega-3 LC-PUFAs levels below the determined reference intervals, while 18 had higher omega-6 LC-PUFAs. The study did not show gender differences in omega-3 and omega-6 LC-PUFAs levels (all p > 0.05). EPA was significantly higher in the 8 year age group compared to those aged 7 and 9 years (median; 0.20 vs 0.17 vs 0.18, respectively, p = 0.049). ARA: EPA ratio was

The Essentiality of Arachidonic Acid in Infant Development

PubMed Central

Hadley, Kevin B.; Ryan, Alan S.; Forsyth, Stewart; Gautier, Sheila; Salem, Norman

2016-01-01

Arachidonic acid (ARA, 20:4n-6) is an n-6 polyunsaturated 20-carbon fatty acid formed by the biosynthesis from linoleic acid (LA, 18:2n-6). This review considers the essential role that ARA plays in infant development. ARA is always present in human milk at a relatively fixed level and is accumulated in tissues throughout the body where it serves several important functions. Without the provision of preformed ARA in human milk or infant formula the growing infant cannot maintain ARA levels from synthetic pathways alone that are sufficient to meet metabolic demand. During late infancy and early childhood the amount of dietary ARA provided by solid foods is low. ARA serves as a precursor to leukotrienes, prostaglandins, and thromboxanes, collectively known as eicosanoids which are important for immunity and immune response. There is strong evidence based on animal and human studies that ARA is critical for infant growth, brain development, and health. These studies also demonstrate the importance of balancing the amounts of ARA and DHA as too much DHA may suppress the benefits provided by ARA. Both ARA and DHA have been added to infant formulas and follow-on formulas for more than two decades. The amounts and ratios of ARA and DHA needed in infant formula are discussed based on an in depth review of the available scientific evidence. PMID:27077882

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.

Control of arachidonic acid release in chick muscle cultures

NASA Technical Reports Server (NTRS)

Templeton, G. H.; Padalino, M.; Wright, W.

1985-01-01

Cultures from thigh muscles of 12 day old embryonic chicks are utilized to examine arachidonic release, prostaglandin (PG) biosynthesis, and protein synthesis. The preparation of the cultures is described. It is observed that exogenous arachidonic acid is formed into photsphatidylethanolamine and phosphatidylcholine, is released by a calcium ionosphere or phospholiphase simulator, and is the substrate for the biosynthesis of PG; the epidermal growth factor and PGF do not stimulate protein synthesis over the basal levels. The relationship between arachidonate release and melittin is studied. The data reveal that a change in intracellular calcium stimulates phospholiphase activity, arachidonate release, and PG synthesis in chick muscle culture.

DNA methylation in an enhancer region of the FADS cluster is associated with FADS activity in human liver.

PubMed

Howard, Timothy D; Mathias, Rasika A; Seeds, Michael C; Herrington, David M; Hixson, James E; Shimmin, Lawrence C; Hawkins, Greg A; Sellers, Matthew; Ainsworth, Hannah C; Sergeant, Susan; Miller, Leslie R; Chilton, Floyd H

2014-01-01

Levels of omega-6 (n-6) and omega-3 (n-3), long chain polyunsaturated fatty acids (LcPUFAs) such as arachidonic acid (AA; 20:4, n-6), eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3) impact a wide range of biological activities, including immune signaling, inflammation, and brain development and function. Two desaturase steps (Δ6, encoded by FADS2 and Δ5, encoded by FADS1) are rate limiting in the conversion of dietary essential 18 carbon PUFAs (18C-PUFAs) such as LA (18:2, n-6) to AA and α-linolenic acid (ALA, 18:3, n-3) to EPA and DHA. GWAS and candidate gene studies have consistently identified genetic variants within FADS1 and FADS2 as determinants of desaturase efficiencies and levels of LcPUFAs in circulating, cellular and breast milk lipids. Importantly, these same variants are documented determinants of important cardiovascular disease risk factors (total, LDL, and HDL cholesterol, triglycerides, CRP and proinflammatory eicosanoids). FADS1 and FADS2 lie head-to-head (5' to 5') in a cluster configuration on chromosome 11 (11q12.2). There is considerable linkage disequilibrium (LD) in this region, where multiple SNPs display association with LcPUFA levels. For instance, rs174537, located ∼ 15 kb downstream of FADS1, is associated with both FADS1 desaturase activity and with circulating AA levels (p-value for AA levels = 5.95 × 10(-46)) in humans. To determine if DNA methylation variation impacts FADS activities, we performed genome-wide allele-specific methylation (ASM) with rs174537 in 144 human liver samples. This approach identified highly significant ASM with CpG sites between FADS1 and FADS2 in a putative enhancer signature region, leading to the hypothesis that the phenotypic associations of rs174537 are likely due to methylation differences. In support of this hypothesis, methylation levels of the most significant probe were strongly associated with FADS1 and, to a lesser degree, FADS2 activities.

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 ).

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

The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans

PubMed Central

2011-01-01

Background Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (FADS) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date. Results In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10-48) and lower DGLA levels (p = 9.80 × 10-11) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (FADS) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10-16 in African Americans, 2.68 × 10-23 in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups. Conclusions We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA. PMID:21599946

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.

A More Desirable Balanced Polyunsaturated Fatty Acid Composition Achieved by Heterologous Expression of Δ15/Δ4 Desaturases in Mammalian Cells

PubMed Central

Zhu, Guiming; Ou, Qin; Zhang, Tao; Jiang, Xudong; Sun, Guozhi; Zhang, Ning; Wang, Kunfu; Fang, Heng; Wang, Mingfu; Sun, Jie; Ge, Tangdong

2013-01-01

Arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are the most biologically active polyunsaturated fatty acids, but their biosyntheses in mammals are very limited. The biosynthesis of DHA is the most difficult, because this undergoes the Sprecher pathway–a further elongation step from docosapentaenoic acid (DPA), a Δ6-desaturase acting on a C24 fatty acid substrate followed by a peroxisomal chain shortening step. This paper reports the successful heterologous expression of two non-mammalian genes (with modification of codon usage), coding for Euglena gracilis Δ4-desaturase and Siganus canaliculatus Δ4-desaturase respectively, in mammalian cells (HEK293 cell line). Both of the Δ4-desaturases can efficiently function, directly converting DPA into DHA. Moreover, the cooperation of the E. gracilis Δ4-desaturase with C. elegans Δ15-desaturase (able to convert a number of n-6 PUFAs to their corresponding n-3 PUFAs) in transgenic HEK293 cells made a more desirable fatty acid composition – a drastically reduced n-6/n-3 PUFAs ratio and a high level of DHA as well as EPA and ARA. Our findings provide a basis for potential applications of the gene constructs for expression of Δ15/Δ4-desaturases in transgenic livestock to produce such a fatty acid profile in the related products, which certainly will bring benefit to human health. PMID:24391980

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

Fatty acids of erythrocyte membrane in acute pancreatitis patients.

PubMed

Kuliaviene, Irma; Gulbinas, Antanas; Cremers, Johannes; Pundzius, Juozas; Kupcinskas, Limas; Dambrauskas, Zilvinas; Jansen, Eugene

2013-09-14

To evaluate changes in the fatty acid composition of erythrocyte membrane phospholipids during severe and mild acute pancreatitis (AP) of alcoholic and nonalcoholic etiology. All consecutive patients with a diagnosis of AP and onset of the disease within the last 72 h admitted to the Hospital of Lithuanian University of Health Sciences between June and December 2007 were included. According to the Acute Physiology and Chronic Health Evaluation (APACHE II) scale, the patients were subdivided into the mild (APACHE II score < 7, n = 22) and severe (APACHE II score ≥ 7, n = 17) AP groups. Healthy individuals (n = 26) were enrolled as controls. Blood samples were collected from patients on admission to the hospital. Fatty acids (FAs) were extracted from erythrocyte phospholipids and expressed as percentages of the total FAs present in the chromatogram. The concentrations of superoxide dismutase and glutathione peroxidase were measured in erythrocytes. We found an increase in the percentages of saturated and monounsaturated FAs, a decrease in the percentages of total polyunsaturated FAs (PUFAs) and n-3 PUFAs in erythrocyte membrane phospholipids of AP patients compared with healthy controls. Palmitic (C16:0), palmitoleic (C16:1n7cis), arachidonic (C20:4n6), docosahexaenoic (DHA, C22:6n3), and docosapentaenoic (DPA, C22:5n3) acids were the major contributing factors. A decrease in the peroxidation and unsaturation indexes in AP patients as well as the severe and mild AP groups as compared with controls was observed. The concentrations of antioxidant enzymes in the mild AP group were lower than in the control group. In severe AP of nonalcoholic etiology, the percentages of arachidic (C20:0) and arachidonic (C20:4n6) acids were decreased as compared with the control group. The patients with mild AP of nonalcoholic etiology had the increased percentages of total saturated FAs and gama linoleic acid (C18:3n6) and the decreased percentages of elaidic (C18:1n9t

Fatty acids of erythrocyte membrane in acute pancreatitis patients

PubMed Central

Kuliaviene, Irma; Gulbinas, Antanas; Cremers, Johannes; Pundzius, Juozas; Kupcinskas, Limas; Dambrauskas, Zilvinas; Jansen, Eugene

2013-01-01

AIM: To evaluate changes in the fatty acid composition of erythrocyte membrane phospholipids during severe and mild acute pancreatitis (AP) of alcoholic and nonalcoholic etiology. METHODS: All consecutive patients with a diagnosis of AP and onset of the disease within the last 72 h admitted to the Hospital of Lithuanian University of Health Sciences between June and December 2007 were included. According to the Acute Physiology and Chronic Health Evaluation (APACHE II) scale, the patients were subdivided into the mild (APACHE II score < 7, n = 22) and severe (APACHE II score ≥ 7, n = 17) AP groups. Healthy individuals (n = 26) were enrolled as controls. Blood samples were collected from patients on admission to the hospital. Fatty acids (FAs) were extracted from erythrocyte phospholipids and expressed as percentages of the total FAs present in the chromatogram. The concentrations of superoxide dismutase and glutathione peroxidase were measured in erythrocytes. RESULTS: We found an increase in the percentages of saturated and monounsaturated FAs, a decrease in the percentages of total polyunsaturated FAs (PUFAs) and n-3 PUFAs in erythrocyte membrane phospholipids of AP patients compared with healthy controls. Palmitic (C16:0), palmitoleic (C16:1n7cis), arachidonic (C20:4n6), docosahexaenoic (DHA, C22:6n3), and docosapentaenoic (DPA, C22:5n3) acids were the major contributing factors. A decrease in the peroxidation and unsaturation indexes in AP patients as well as the severe and mild AP groups as compared with controls was observed. The concentrations of antioxidant enzymes in the mild AP group were lower than in the control group. In severe AP of nonalcoholic etiology, the percentages of arachidic (C20:0) and arachidonic (C20:4n6) acids were decreased as compared with the control group. The patients with mild AP of nonalcoholic etiology had the increased percentages of total saturated FAs and gama linoleic acid (C18:3n6) and the decreased percentages of elaidic

Omega-3 and omega-6 polyunsaturated fatty acids enhance arsenic trioxide efficacy in arsenic trioxide-resistant leukemic and solid tumor cells.

PubMed

Wirtitsch, Melanie; Roth, Erich; Bachleitner-Hofmann, Thomas; Wessner, Barbara; Sturlan, Sanda

2009-01-01

Recently we showed that the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) sensitizes arsenic trioxide (As2O3)-resistant tumor cells to a clinically achievable concentration (1 microM) of As2O3 via a reactive oxygen species (ROS)-dependent mechanism. The aim of the present study was to evaluate, whether this combined effect of As2O3 and DHA is also applicable to other PUFAs [i.e., eicospentaenoic acid (EPA), arachidonic acid (AA), and gamma-linolenic acid (GLA)]. Fourteen tumor cell lines were incubated with As2O3 (1 microM), PUFA (25-100 microM), or the combination thereof (+/- vitamin E). Cell viability (colorimetric), apoptosis (bivariate annexin V/propidium iodide staining, detection of hypodiploid DNA), and thiobarbituric acid reactive substances (TBARS) were evaluated. Twelve of 14 As2O3-resistant cell lines tested were resistant to PUFA monotherapy. However, combined treatment with As2O3 and either PUFA significantly reduced cell viability in a dose-dependent manner with AA being the most potent As2O3 enhancer. The combined cytotoxic effect of As2O3/AA treatment was due to induction of apoptosis, preceded by increased intracellular TBARS and was abolished by the antioxidant vitamin E. Importantly, the combined effect of As2O3 and AA was selectively toxic for malignant cells because no cytotoxic effect was observed in normal skin fibroblasts and human microvascular endothelial cells. In conclusion, our study shows that also other PUFAs than DHA-and in particular the omega-6-PUFA AA--can be used as effective modulators of tumor cell chemosensitivity to clinically achievable concentrations of As2O3. Enhanced lipid peroxidation most likely constitutes the key mechanism for the combined effect.

Associations between long chain polyunsaturated fatty acids and cardiovascular lipid risk factors in youth with type 1 diabetes: SEARCH Nutrition Ancillary Study.

PubMed

Couch, Sarah C; Crandell, Jamie; King, Irena; Peairs, Abigail; Shah, Amy S; Dolan, Lawrence M; Tooze, Janet; Crume, Tessa; Mayer-Davis, Elizabeth

2017-01-01

In this longitudinal study we explored the relationships between plasma n-3 and n-6 polyunsaturated fatty acids (PUFAs) and Δ5 and Δ6 desaturase activities (D5D and D6D, respectively) and fasting lipids in youth with type 1 diabetes (T1D). Incident cases of T1D in youth <20years of age who were seen for a baseline study visit (N=914) and a 1-year follow-up visit (N=416) were included. Fasting blood samples were obtained at each visit and plasma phospholipid n-6 PUFAs were measured, which included linoleic acid (LA), dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA); n-3 PUFAs included α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Estimated D5D and D6D were calculated as FA product-to-precursor ratios, where D5D=AA/DGLA and D6D=DGLA/LA. To examine the longitudinal relationships between long chain PUFAs, desaturase activities and fasting plasma lipids in youth with T1D mixed effects models were used for each individual PUFAs, D5D and D6D, adjusted for demographics, clinic site, diabetes duration, insulin regimen, insulin dose/kg, HbA1c, insulin sensitivity score, and body mass index with random effects to account for the repeated measurements. Favorable lipid associations were found between LA and low-density lipoprotein (LDL) cholesterol (β=-0.58, p<0.05); AA, plasma triglycerides (TG) (β=-0.04, p<0.05) and TG/high-density lipoprotein (HDL)-C ratio (β=-0.04, p<0.05); and D5D, plasma TG (β=-0.2, p<0.05) and TG/HDL-cholesterol ratio (β=-0.23, p<0.05). Findings were mixed for the n-3 PUFAs and DGLA: ALA was positively associated with plasma TG (β=0.33, p<0.05) and HDL cholesterol (β=9.86, p<0.05); EPA was positively associated with total cholesterol (β=8.17, p<0.05), LDL cholesterol (β=5.74, p<0.01) and HDL cholesterol (β=2.27, p<0.01); and DGLA was positively associated with TG/HDL-cholesterol ratio (β=0.05, P<0.05). Findings suggest that the most abundant PUFA, LA as well as its metabolic bi-product AA, may

Transfer of arachidonate from phosphatidylcholine to phosphatidylethanolamine and triacylglycerol in guinea pig alveolar macrophages

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

Nijssen, J.G.; Oosting, R.S.; Nkamp, F.Pv.

1986-10-01

Guinea pig alveolar macrophages were labeled by incubation with either arachidonate or linoleate. Arachidonate labeled phosphatidylcholine (PC), phosphatidylethanolamine (PE) and triglycerides (TG) equally well, with each lipid containing about 30% of total cellular radioactivity. In comparison to arachidonate, linoleate was recovered significantly less in PE (7%) and more in TG (47%). To investigate whether redistributions of acyl chains among lipid classes took place, the macrophages were incubated with 1-acyl-2-(1-/sup 14/C)arachidonoyl PC or 1-acyl-2-(1-/sup 14/C)linoleoyl PC. After harvesting, the cells incubated with 1-acyl-2-(1-/sup 14/C)linoleoyl PC contained 86% of the recovered cellular radioactivity in PC, with only small amounts of label beingmore » transferred to PE and TG (3 and 6%, respectively). More extensive redistributions were observed with arachidonate-labeled PC. In this case, only 60% of cellular radioactivity was still associated with PC, while 22 and 12%, respectively, had been transferred to PE and TG. Arachidonate transfer from PC to PE was unaffected by an excess of free arachidonate which inhibited this transfer to TG for over 90%, indicating that different mechanisms or arachidonoyl CoA pools were involved in the transfer of arachidonate from PC to PE and TG. Cells prelabeled with 1-acyl-2-(1-/sup 14/C)arachidonoyl PC released /sup 14/C-label into the medium upon further incubation. This release was slightly stimulated by zymosan and threefold higher in the presence of the Ca2+-ionophore A23187. Labeling of macrophages with intact phospholipid molecules appears to be a suitable method for studying acyl chain redistribution and release reactions.« less

Cooking with soyabean oil increases whole-blood α-linolenic acid in school-aged children: results from a randomized trial.

PubMed

Villamor, Eduardo; Marín, Constanza; Mora-Plazas, Mercedes; Casale, Mia; Vargas, Luz N; Baylin, Ana

2015-12-01

Supply of essential n-3 PUFA is limited worldwide. While fish-oil supplementation effectively improves n-3 PUFA status, it may not be a sustainable intervention. The use of α-linolenic acid (ALA)-rich cooking oils in the household may be a suitable alternative but its effect on PUFA status is unclear. We aimed to compare the effect of providing families with soyabean oil, an ALA-rich cooking oil, v. sunflower oil on whole-blood PUFA levels of children aged 11-18 years. In a randomized, masked, parallel trial, we assigned families to receive a one-month supply of either soyabean or sunflower oil. Fatty acid concentrations were quantified in whole-blood samples obtained from the children before and at the end of the intervention. Changes in fatty acids were compared between treatment arms with use of linear regression for repeated measures. Sixty low- and middle-income families. Bogotá, Colombia. Soyabean oil significantly increased ALA concentrations by 0.05 percentage points of total serum fatty acids whereas sunflower oil decreased them by 0.12 percentage points (soyabean v. sunflower oil effect=0.17; 95% CI 0.11, 0.24). Concentrations of both n-3 and n-6 very-long-chain PUFA, including docosapentaenoic acid, DHA, dihomo-γ-linolenic acid and arachidonic acid, increased significantly in both intervention arms. Levels of oleic acid and palmitic acid decreased, irrespective of oil assignment. Total energy or energy intake from saturated fat did not change. Replacing cooking oils at the household level is an effective intervention to improve essential PUFA status of children.

In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation.

PubMed

Maes, Michael; Mihaylova, Ivana; Leunis, Jean-Claude

2005-12-01

There is now evidence that major depression is accompanied by decreased levels of omega3 poly-unsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There is a strong comorbidity between major depression and chronic fatigue syndrome (CFS). The present study has been carried out in order to examine PUFA levels in CFS. In twenty-two CFS patients and 12 normal controls we measured serum PUFA levels using gas chromatography and mass spectrometry. We found that CFS was accompanied by increased levels of omega6 PUFAs, i.e. linoleic acid and arachidonic acid (AA), and mono-unsaturated fatty acids (MUFAs), i.e. oleic acid. The EPA/AA and total omega3/omega6 ratios were significantly lower in CFS patients than in normal controls. The omega3/omega6 ratio was significantly and negatively correlated to the severity of illness and some items of the FibroFatigue scale, i.e. aches and pain, fatigue and failing memory. The severity of illness was significantly and positively correlated to linoleic and arachidonic acid, oleic acid, omega9 fatty acids and one of the saturated fatty acids, i.e. palmitic acid. In CFS subjects, we found significant positive correlations between the omega3/omega6 ratio and lowered serum zinc levels and the lowered mitogen-stimulated CD69 expression on CD3+, CD3+ CD4+, and CD3+ CD8+ T cells, which indicate defects in early T cell activation. The results of this study show that a decreased availability of omega3 PUFAs plays a role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favourably to treatment with--amongst other things--omega3 PUFAs, such as EPA and DHA.

A safflower oil based high-fat/high-sucrose diet modulates the gut microbiota and liver phospholipid profiles associated with early glucose intolerance in the absence of tissue inflammation.

PubMed

Danneskiold-Samsøe, Niels Banhos; Andersen, Daniel; Radulescu, Ilinca Daria; Normann-Hansen, Ann; Brejnrod, Asker; Kragh, Marie; Madsen, Tobias; Nielsen, Christian; Josefsen, Knud; Fretté, Xavier; Fjaere, Even; Madsen, Lise; Hellgren, Lars I; Brix, Susanne; Kristiansen, Karsten

2017-05-01

Omega-6 (n-6) PUFA-rich diets are generally considered obesogenic in rodents. Here, we examined how long-term intake of a high-fat/high-sucrose (HF/HS) diet based on safflower oil affected metabolism, inflammation, and gut microbiota composition. We fed male C57BL/6J mice a HF/HS diet based on safflower oil-rich in n-6 PUFAs-or a low-fat/low-sucrose diet for 40 wk. Compared to the low-fat/low-sucrose diet, intake of the safflower-based HF/HS diet only led to moderate weight gain, while glucose intolerance developed at week 5 prior to signs of inflammation, but concurrent with increased levels of linoleic acid and arachidonic acid in hepatic phospholipids. Intake of the HF/HS diet resulted in early changes in the gut microbiota, including an increased abundance of Blautia, while late changes coincided with altered inflammatory profiles and increased fasting plasma insulin. Analysis of immune cells in visceral fat and liver revealed no differences between diets before week 40, where the number of immune cells decreased in the liver of HF/HS-fed mice. We suggest that a diet-dependent increase in the n-6 to omega-3 (n-3) PUFA ratio in hepatic phospholipids together with gut microbiota changes contributed to early development of glucose intolerance without signs of inflammation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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.

Physiological aspects of human milk lipids.

PubMed

Koletzko, B; Rodriguez-Palmero, M; Demmelmair, H; Fidler, N; Jensen, R; Sauerwald, T

2001-11-01

Human milk from healthy and well-nourished mothers is the preferred form of feeding for all healthy newborn infants. The nutrient supply with human milk supports normal growth and development of the infant. Here the general characteristics of human milk lipids and recent knowledge on lactational physiology, composition and functional aspects of human milk lipids are discussed. Lipids in human milk represent the main source of energy for the breastfed baby and supply essential nutrients such as fat-soluble vitamins and polyunsaturated fatty acids (PUFA). The essential fatty acids linoleic and alpha-linolenic acids (LA and ALA) are precursors of long-chain polyunsaturated fatty acids (LC-PUFA), including arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acids (AA and DHA). LC-PUFA serve as indispensable structural components of cellular membranes and are deposited to a considerable extent in the growing brain and the retina during perinatal development. The supply of preformed LC-PUFA with human milk lipids has been related to functional outcomes of the recipient infants such as visual acuity and development of cognitive functions during the first year of life. Recent stable isotope studies indicate that the major portion of milk PUFA is not derived directly from the maternal diet, but stems from endogenous body stores. Thus, not only the woman's current but also her long-term dietary intake is of marked relevance for milk fat composition.

Comparison in nutritional quality between wild and cultured cuttlefish Sepia pharaonis

NASA Astrophysics Data System (ADS)

Wen, Jing; Chen, Daohai; Zeng, Ling

2014-01-01

In this study, the proximate composition and the amino and fatty acid profiles of shrimp Litopenaeus vannamei (prey) and wild and cultured cuttlefish Sepia pharaonis (the latter fed the prey) were determined and compared with FAO/WHO recommendations. The resulting scores for isoleucine, phenylalanine+tyrosine, histidine, lysine, threonine, and tryptophan in cultured cuttlefish were ≥150. The ratio of EAA (essential amino acids)/nonessential amino acids in cultured cuttlefish (0.82) was higher than in the wild form (0.80). All EAA amino acid scores for cultured cuttlefish were higher than their wild counterparts, except for histidine and tryptophan. Both groups of cuttlefish possessed similar saturated fatty acid content, with the cultured containing much more total (Σ) monounsaturated fatty acids, Σ n-6 polyunsaturated fatty acids (PUFA), and eicosapentaenoic acid (C20:5 n-3) but less Σ n-3 PUFA, arachidonic acid (C20:4 n-6), and docosahexaenoic acid (C22:6 n-3) than their wild counterparts. Therefore, the present results suggest that these cultured cuttlefish were better than the wild form for human health. Notably, these results also indicate that the nutritional composition of these cuttlefish might have been significantly affected by diet.

Oral feeding with polyunsaturated fatty acids fosters hematopoiesis and thrombopoiesis in healthy and bone marrow-transplanted mice.

PubMed

Limbkar, Kedar; Dhenge, Ankita; Jadhav, Dipesh D; Thulasiram, Hirekodathakallu V; Kale, Vaijayanti; Limaye, Lalita

2017-09-01

Hematopoietic stem cells play the vital role of maintaining appropriate levels of cells in blood. Therefore, regulation of their fate is essential for their effective therapeutic use. Here we report the role of polyunsaturated fatty acids (PUFAs) in regulating hematopoiesis which has not been explored well so far. Mice were fed daily for 10 days with n-6/n-3 PUFAs, viz. linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid and docosahexanoic acid (DHA) in four separate test groups with phosphate-buffered saline fed mice as control set. The bone marrow cells of PUFA-fed mice showed a significantly higher hematopoiesis as assessed using side population, Lin-Sca-1 + ckit+, colony-forming unit (CFU), long-term culture, CFU-spleen assay and engraftment potential as compared to the control set. Thrombopoiesis was also stimulated in PUFA-fed mice. A combination of DHA and AA was found to be more effective than when either was fed individually. Higher incorporation of PUFAs as well as products of their metabolism was observed in the bone marrow cells of PUFA-fed mice. A stimulation of the Wnt, CXCR4 and Notch1 pathways was observed in PUFA-fed mice. The clinical relevance of this study was evident when bone marrow-transplanted recipient mice, which were fed with PUFAs, showed higher engraftment of donor cells, suggesting that the bone marrow microenvironment may also be stimulated by feeding with PUFAs. These data indicate that oral administration of PUFAs in mice stimulates hematopoiesis and thrombopoiesis and could serve as a valuable supplemental therapy in situations of hematopoietic failure. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

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...

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.

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.

Use of radiolabeled substrates to determine the desaturase and elongase activities involved in eicosapentaenoic acid and docosahexaenoic acid biosynthesis in the marine microalga Pavlova lutheri.

PubMed

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

2013-06-01

The marine flagellate Pavlova lutheri is a microalga known to be rich in long-chain polyunsaturated fatty acids (LC-PUFAs) and able to produce large amounts of n-3 fatty acids, such as eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). As no previous study had attempted to measure the metabolic step of fatty acid synthesis in this alga, we used radiolabeled precursors to explore the various desaturation and elongation steps involved in LC-PUFA biosynthesis pathways. The incorporation of (14)C-labeled palmitic ([1-(14)C] 16:0) and dihomo-γ-linolenic ([1-(14)C] 20:3n-6) acids as ammonium salts within the cells was monitored during incubation periods lasting 3, 10 or 24h. Total lipids and each of the fatty acids were also monitored during these incubation periods. A decrease in the availability and/or accessibility of the radiolabeled substrates was observed over the incubation time. This decrease with incubation time observed using [1-(14)C] 16:0 and [1-(14)C] 20:3n-6 as substrates was used to monitor the conversion of (14)C-labeled arachidonic acid ([1-(14)C] 20:4n-6) into longer and more unsaturated fatty acids, such as 20:5n-3 and 22:6n-3, over shorter incubation times (1 and 3h). A metabolic relationship between the n-6 and n-3 fatty acid series was demonstrated in P. lutheri by measuring the Δ17-desaturation activity involved in the conversion of eicosatetraenoic acid to 20:5n-3. Our findings suggest that the biosynthesis pathway leading to n-3 LC-PUFA involves fatty acids of the n-6 family, which act as precursors in the biosynthesis of 20:5n-3 and 22:6n-3. This preliminary work provides a method for studying microalgal LC-PUFA biosynthesis pathways and desaturase and elongase activities in vivo using externally-radiolabeled fatty acid precursors as substrates. The use of the [1-(14)C] 20:4n-6 substrate also highlighted the relationships between the n-6 and the n-3 fatty acid series (e.g. Δ17-desaturation), and the final elongation

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

Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature

PubMed Central

Norambuena, Fernando; Morais, Sofia; Emery, James A.; Turchini, Giovanni M.

2015-01-01

Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad–time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature

Associations of cord blood fatty acids with lymphocyte proliferation, IL-13, and IFN-γ

PubMed Central

Gold, Diane R.; Willwerth, Ben M.; Tantisira, Kelan G.; Finn, Patricia W.; Schaub, Bianca; Perkins, David L.; Tzianabos, Arthur; Ly, Ngoc P.; Schroeter, Christian; Gibbons, Fiona; Campos, Hannia; Oken, Emily; Gillman, Matthew W.; Palmer, Lyle J.; Ryan, Louise M.; Weiss, Scott T.

2006-01-01

Background. N-3 and n-6 polyunsaturated fatty acids (PUFAs) have been hypothesized to have opposing influences on neonatal immune responses that might influence the risk of allergy or asthma. However, both n-3 eicosapentaenoic acid (EPA) and n-6 arachidonic acid (AA) are required for normal fetal development. Objective. We evaluated whether cord blood fatty acid levels were related to neonatal immune responses and whether n-3 and n-6 PUFA responses differed. Methods. We examined the relation of cord blood plasma n-3 and n-6 PUFAs (n = 192) to antigen- and mitogen-stimulated cord blood lymphocyte proliferation (n = 191) and cytokine (IL-13 and IFN-γ; n = 167) secretion in a US birth cohort. Results. Higher levels of n-6 linoleic acid were correlated with higher IL-13 levels in response to Bla g 2 (cockroach, P = .009) and Der f 1 (dust mite, P = .02). Higher n-3 EPA and n-6 AA levels were each correlated with reduced lymphocyte proliferation and IFN-γ levels in response to Bla g 2 and Der f 1 stimulation. Controlling for potential confounders, EPA and AA had similar independent effects on reduced allergen-stimulated IFN-γ levels. If neonates had either EPA or AA levels in the highest quartile, their Der f 1 IFN-γ levels were 90% lower (P = .0001) than those with both EPA and AA levels in the lowest 3 quartiles. Reduced AA/EPA ratio was associated with reduced allergen-stimulated IFN-γ level. Conclusion. Increased levels of fetal n-3 EPA and n-6 AA might have similar effects on attenuation of cord blood lymphocyte proliferation and IFN-γ secretion. Clinical implications. The implications of these findings for PMID:16630954

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.

The discovery and early structural studies of arachidonic acid

PubMed Central

Martin, Sarah A.; Brash, Alan R.; Murphy, Robert C.

2016-01-01

Arachidonic acid and esterified arachidonate are ubiquitous components of every mammalian cell. This polyunsaturated fatty acid serves very important biochemical roles, including being the direct precursor of bioactive lipid mediators such as prostaglandin and leukotrienes. This 20 carbon fatty acid with four double bonds was first isolated and identified from mammalian tissues in 1909 by Percival Hartley. This was accomplished prior to the advent of chromatography or any spectroscopic methodology (MS, infrared, UV, or NMR). The name, arachidonic, was suggested in 1913 based on its relationship to the well-known arachidic acid (C20:0). It took until 1940 before the positions of the four double bonds were defined at 5,8,11,14 of the 20-carbon chain. Total synthesis was reported in 1961 and, finally, the configuration of the double bonds was confirmed as all-cis-5,8,11,14. By the 1930s, the relationship of arachidonic acid within the family of essential fatty acids helped cue an understanding of its structure and the biosynthetic pathway. Herein, we review the findings leading up to the discovery of arachidonic acid and the progress toward its complete structural elucidation. PMID:27142391

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.

The Pattern of Fatty Acids Displaced by EPA and DHA Following 12 Months Supplementation Varies between Blood Cell and Plasma Fractions.

PubMed

Walker, Celia G; West, Annette L; Browning, Lucy M; Madden, Jackie; Gambell, Joanna M; Jebb, Susan A; Calder, Philip C

2015-08-03

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0-4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify important FA changes for plasma phosphatidylcholine (PC), cholesteryl ester (CE) and triglyceride (TAG) and for blood mononuclear cells (MNC), red blood cells (RBC) and platelets (PLAT). Dose-dependent increases in EPA + DHA were matched by decreases in several n-6 polyunsaturated fatty acids (PUFA) in PC, CE, RBC and PLAT, but were predominantly compensated for by oleic acid in TAG. Changes were observed for all FA classes in MNC. Consequently the n-6:n-3 PUFA ratio was reduced in a dose-dependent manner in all pools after 12 months (37%-64% of placebo in the four portions group). We conclude that the profile of the FA decreased in exchange for the increase in EPA + DHA following supplementation differs by FA pool with implications for understanding the impact of n-3 PUFA on blood lipid and blood cell biology.

The Pattern of Fatty Acids Displaced by EPA and DHA Following 12 Months Supplementation Varies between Blood Cell and Plasma Fractions

PubMed Central

Walker, Celia G.; West, Annette L.; Browning, Lucy M.; Madden, Jackie; Gambell, Joanna M.; Jebb, Susan A.; Calder, Philip C.

2015-01-01

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0–4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify important FA changes for plasma phosphatidylcholine (PC), cholesteryl ester (CE) and triglyceride (TAG) and for blood mononuclear cells (MNC), red blood cells (RBC) and platelets (PLAT). Dose-dependent increases in EPA + DHA were matched by decreases in several n-6 polyunsaturated fatty acids (PUFA) in PC, CE, RBC and PLAT, but were predominantly compensated for by oleic acid in TAG. Changes were observed for all FA classes in MNC. Consequently the n-6:n-3 PUFA ratio was reduced in a dose-dependent manner in all pools after 12 months (37%–64% of placebo in the four portions group). We conclude that the profile of the FA decreased in exchange for the increase in EPA + DHA following supplementation differs by FA pool with implications for understanding the impact of n-3 PUFA on blood lipid and blood cell biology. PMID:26247960

Data on the effect of oral feeding of Arachidonic acid or Docosahexanoic acid on haematopoiesis in mice.

PubMed

Limbkar, Kedar; Dhenge, Ankita; Jadhav, Dipesh D; Thulasiram, Hirekodathakallu V; Kale, Vaijayanti; Limaye, Lalita

2017-10-01

Stem cells have peculiar property to self-renew and differentiate. It is important to control their fate in safe and effective ways for their therapeutic use. The mediators of essential polyunsaturated fatty acids (PUFAs) namely Arachidonic acid (AA) and Docosahexanoic acid (DHA) are known to play a role in haematopoiesis via various metabolic pathways [1]. However the direct effect of purified AA or DHA on haematopoiesis has not been well investigated yet. We have reported that oral administration of PUFAs enhanced haematopoiesis in mice [2]. Signaling Leukocyte Antigen Molecule (SLAM) (CD48 - CD150 + ) phenotype consists of pure population of haematopoietic stem cells (HSCs). Herein we observed higher percentage of SLAM (CD48 - CD150 + ) phenotype in the bone marrow (BM) cells of mice fed with AA or DHA compared to PBS fed control mice. Data from engraftment study depicts that BM from AA/DHA-fed mice showed higher absolute number of donor cells in recipient mice compared to control. The enhanced hematopoiesis observed in AA/DHA-fed mice was returned to normal when the mice were kept on normal diet for six weeks (after ten days of oral feeding). We confirmed GCMS (Gas Chromatography-Mass Spectroscopy) retention times of AA and DHA by co-injecting fatty acid extract from AA or DHA fed mice with purified AA or DHA standards respectively. Representative flow cytometry profile of Lin - Sca-1 + c-kit + (LSK) cells showed higher expression of CXCR4 protein and ligands of Wnt, Notch1 signaling in BM of AA/DHA-fed mice.

Lipid content in hepatic and gonadal adipose tissue parallel aortic cholesterol accumulation in mice fed diets with different omega-6 PUFA to EPA plus DHA ratios

USDA-ARS?s Scientific Manuscript database

Diets with low omega (u)-6 polyunsaturated fatty acids (PUFA) to eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) ratios have been shown to decrease aortic cholesterol accumulation and have been suggested to promote weight loss. The involvement of the liver and gonadal adipose tissue (GAT...

Fatty acids in breast milk associated with asthma-like symptoms and atopy in infancy: a longitudinal study.

PubMed

Soto-Ramírez, Nelís; Karmaus, Wilfried; Zhang, Hongmei; Liu, Jihong; Billings, Deborah; Gangur, Venugopal; Amrol, David; da Costa, Kerry-Ann; Davis, Susan; Goetzl, Laura

2012-11-01

The relationship between fatty acids (FAs) in breast milk and the risk of childhood allergies is controversial. We prospectively investigated the relationship between FAs in colostrum and breast milk and asthma-like symptoms (AS) and atopy in infancy. Pregnant women were recruited in Columbia and Charleston, South Carolina. Colostrum and mature milk samples were collected. The concentrations of n-3 FAs (eicosapentaenoic acid, α-linolenic acid, docosapentaenoic acid, and docosahexaenoic acid) and n-6 FAs (linoleic acid, arachidonic acid, and eicosadienoic acid) were determined by gas chromatography. AS were ascertained at 6 and 12 months of age and atopy (skin prick test) at 12 months. FAs were dichotomized (high vs. median and low). Generalized estimating equations were used to determine the effect of FAs on repeated AS, compensating for intra-individual correlations and adjusting for confounders. Log-linear regression was used to analyze atopy. FAs were analyzed in 24 colostrum and 78 breast milk samples. High levels of total n-6 (lipid based) FAs in breast milk were associated with an increased risk of AS in infants (risk ratio (RR) = 2.91; 95% confidence interval (CI): 1.37, 6.18), even after controlling for total n-3 FAs (RR = 2.07, 95% CI: 1.12, 3.85). High levels of total n-3 FAs controlling for n-6 FAs decreased the risk of atopy at the age of 12 months. High levels of total n-6 polyunsaturated fatty acids (PUFAs) in breast milk are associated with an increased risk for AS, whereas high levels of total n-3 PUFAs decreased the risk of atopy. These data suggest that the effects of n-3 and n-6 PUFAs on allergic disorders should be further explored.

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.

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

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

Lower omega-3 polyunsaturated fatty acids and lower docosahexaenoic acid in men with pedophilia.

PubMed

Mincke, Elda; Cosyns, Paul; Christophe, Armand B; De Vriese, Stephanie; Maes, Michael

2006-12-01

Previous studies have suggested that abnormalities in plasma phospholipid fatty acids may play a role in aggressive behavior. Recently, it was suggested that a dysfunctional serotonergic turnover in the brain may be involved in the etiopathology of pedophilia. Depletion of n-3 polyunsaturated fatty acids (PUFA) may cause alterations in the serotonergic system that may be related to pedophilia and aggression. This study examines the serum phospholipid n-3 and n-6 PUFA fractions in pedophilia. Twenty-seven pedophilic men and eighteen healthy volunteers participated in this study. In pedophilia there was a significant depletion of the C22:6n-3 (docosahexaenoic acid, DHA), total n-3 fractions and an increase in the total n-6/n-3 and C20:4n-6/C20:5n-3 (arachidonic acid/eicosapentaenoic acid) ratios. Using the NEO Personality Inventory, lower DHA in pedophiles is related to more impulsiveness and lower agreeableness (trust, altruism, straightforwardness, compliance) and conscientiousness (self-discipline). The results of this study suggest that a depletion of the serum phospholipid n-3 higher unsaturated fatty acids (HUFAs) and, in particular, of DHA may take part in the pathophysiology of pedophilia. One hypothesis is that a depletion of n-3 HUFAs and DHA may cause alterations in the serotonergic turnover, which are related to impulse discontrol and aggression-hostility, behaviors which are associated with pedophilia.

Dietary arachidonic acid and docosahexaenoic acid regulate liver fatty acid desaturase (FADS) alternative transcript expression in suckling piglets.

PubMed

Wijendran, Vasuki; Downs, Ian; Srigley, Cynthia Tyburczy; Kothapalli, Kumar S D; Park, Woo Jung; Blank, Bryant S; Zimmer, J Paul; Butt, C M; Salem, Norman; Brenna, J Thomas

2013-10-01

Molecular regulation of fatty acid desaturase (Fads) gene expression by dietary arachidonic acid (ARA) and docosahexaenoic acid (DHA) during early post-natal period, when the demand for long chain polyunsaturated fatty acids (LC-PUFA) is very high, has not been well defined. The objective of the current study was to determine regulation of liver Fads1, Fads2 and Fads3 classical (CS) and alternative transcripts (AT) expression by dietary ARA and DHA, within the physiological range present in human breast milk, in suckling piglets. Piglets were fed one of six milk replacer formula diets (formula-reared groups, FR) with varying ARA and DHA content from days 3-28 of age. The ARA/DHA levels of the six formula diets were as follows (% total fatty acid, FA/FA): (A1) 0.1/1.0; (A2) 0.53/1.0; (A3-D3) 0.69/1.0; (A4) 1.1/1.0; (D2) 0.67/0.62; and (D1) 0.66/0.33. The control maternal-reared (MR) group remained with the dam. Fads1 expression was not significantly different between FR and MR groups. Fads2 expression was down-regulated significantly in diets with 1:1 ratio of ARA:DHA, compared to MR. Fads2 AT1 expression was highly correlated to Fads2 expression. Fads3 AT7 was the only Fads3 transcript sensitive to dietary LC-PUFA intake and was up-regulated in the formula diets with lowest ARA and DHA contents compared to MR. Thus, the present study provides evidence that the proportion of dietary ARA:DHA is a significant determinant of Fads2 expression and LC-PUFA metabolism during the early postnatal period. Further, the data suggest that Fads3 AT7 may have functional significance when dietary supply of ARA and DHA are low during early development. © 2013 Elsevier Ltd. All rights reserved.

Prenatal exposure to methyl mercury from fish consumption and polyunsaturated fatty acids: associations with child development at 20 mo of age in an observational study in the Republic of Seychelles.

PubMed

Strain, J J; Yeates, Alison J; van Wijngaarden, Edwin; Thurston, Sally W; Mulhern, Maria S; McSorley, Emeir M; Watson, Gene E; Love, Tanzy M; Smith, Tristram H; Yost, Kelley; Harrington, Donald; Shamlaye, Conrad F; Henderson, Juliette; Myers, Gary J; Davidson, Philip W

2015-03-01

Fish is a rich source of n-3 polyunsaturated fatty acids (PUFAs) but also contains the neurotoxicant methyl mercury (MeHg). PUFAs may modify the relation between prenatal MeHg exposure and child development either directly by enhancing neurodevelopment or indirectly through the inflammatory milieu. The objective was to investigate the associations of prenatal MeHg exposure and maternal PUFA status with child development at 20 mo of age. The Seychelles Child Development Study Nutrition Cohort 2 is an observational study in the Republic of Seychelles, a high-fish-eating population. Mothers were enrolled during pregnancy and their children evaluated at 20 mo of age by using the Bayley Scales of Infant Development II (BSID-II), the MacArthur Bates Communicative Development Inventories (CDI), and the Infant Behavior Questionnaire-Revised. There were 1265 mother-child pairs with complete data. Prenatal MeHg exposure had no direct associations with neurodevelopmental outcomes. Significant interactions were found between MeHg and PUFAs on the Psychomotor Developmental Index (PDI) of the BSID-II. Increasing MeHg was associated with lower PDI but only in children of mothers with higher n-6/n-3. Among mothers with higher n-3 PUFAs, increasing MeHg was associated with improved PDI. Higher maternal docosahexaenoic acid (DHA) was associated with improved CDI total gestures (language development) but was significantly adversely associated with the Mental Development Index (MDI), both with and without MeHg adjustment. Higher n-6:n-3 ratios were associated with poorer scores on all 3 CDI outcomes. We found no overall adverse association between prenatal MeHg exposure and neurodevelopmental outcomes. However, maternal PUFA status as a putative marker of the inflammatory milieu appeared to modify the associations of prenatal MeHg exposure with the PDI. Increasing DHA status was positively associated with language development yet negatively associated with the MDI. These findings may

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.

Associations between long chain polyunsaturated fatty acids and cardiovascular lipid risk factors in youth with type 1 diabetes: SEARCH Nutrition Ancillary Study

PubMed Central

Couch, Sarah C.; Crandell, Jamie; King, Irena; Peairs, Abigail; Shah, Amy S; Dolan, Lawrence M; Tooze, Janet; Crume, Tessa; Mayer-Davis, Elizabeth

2017-01-01

Purpose In this longitudinal study we explored the relationships between plasma n-3 and n-6 polyunsaturated fatty acids (PUFAs) and Δ5 and Δ6 desaturase activities (D5D and D6D, respectively) and fasting lipids in youth with type 1 diabetes (T1D). Methods Incident cases of T1D in youth <20 years of age who were seen for a baseline study visit (N=914) and a 1-year follow-up visit (N=416) were included. Fasting blood samples were obtained at each visit and plasma phospholipid n-6 PUFAs were measured, which included linoleic acid (LA), dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA); n-3 PUFAs included α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Estimated D5D and D6D were calculated as FA product-to-precursor ratios, where D5D= AA/DGLA and D6D = DGLA/LA. To examine the longitudinal relationships between long chain PUFAs, desaturase activities and fasting plasma lipids in youth with T1D mixed effects models were used for each individual PUFAs, D5D and D6D, adjusted for demographics, clinic site, diabetes duration, insulin regimen, insulin dose/kg, HbA1c, insulin sensitivity score, and body mass index with random effects to account for the repeated measurements. Findings Favorable lipid associations were found between LA and low-density lipoprotein (LDL) cholesterol (β= −0.58, P<0.05); AA, plasma triglycerides (TG) (β= −0.04, P<0.05) and TG/ high-density lipoprotein (HDL)-C ratio (β= −0.04, P<0.05); and D5D, plasma TG (β= −0.2, P<0.05) and TG/HDL-cholesterol ratio (β= −0.23, P<0.05). Findings were mixed for the n-3 PUFAs and DGLA: ALA was positively associated with plasma TG (β= 0.33, P<0.05) and HDL cholesterol (β= 9.86, P<0.05); EPA was positively associated with total cholesterol (β= 8.17, P<0.05), LDL cholesterol (β=5.74, P<0.01) and HDL cholesterol (β= 2.27, P<0.01); and DGLA was positively associated with TG/HDL-cholesterol ratio (β= 0.05, P<0.05) Conclusion Findings suggest that the most

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.

The increased level of COX-dependent arachidonic acid metabolism in blood platelets from secondary progressive multiple sclerosis patients.

PubMed

Morel, Agnieszka; Miller, Elzbieta; Bijak, Michal; Saluk, Joanna

2016-09-01

Platelet activation is increasingly postulated as a possible component of the pathogenesis of multiple sclerosis (MS), especially due to the increased risk of cardiovascular events in MS. Arachidonic acid cascade metabolized by cyclooxygenase (COX) is a key pathway of platelet activation. The aim of our study was to investigate the COX-dependent arachidonic acid metabolic pathway in blood platelets from secondary progressive multiple sclerosis (SP MS) patients. The blood samples were obtained from 50 patients (man n = 22; female n = 28), suffering from SP MS, diagnosed according to the revised McDonald criteria. Platelet aggregation was measured in platelet-rich plasma after arachidonic acid stimulation. The level of COX activity and thromboxane B2 concentration were determined by ELISA method. Lipid peroxidation was assessed by measuring the level of malondialdehyde. The results were compared with a control group of healthy volunteers. We found that blood platelets obtained from SP MS patients were more sensitive to arachidonic acid and their response measured as platelet aggregation was stronger (about 14 %) relative to control. We also observed a significantly increased activity of COX (about 40 %) and synthesis of thromboxane B2 (about 113 %). The generation of malondialdehyde as a marker of lipid peroxidation was about 10 % higher in SP MS than in control. Cyclooxygenase-dependent arachidonic acid metabolism is significantly increased in blood platelets of patients with SP MS. Future clinical studies are required to recommend the use of low-dose aspirin, and possibly other COX inhibitors in the prevention of cardiovascular risk in MS.

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.

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.

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.

Maternal nutritional determinants of colostrum fatty acids in the EDEN mother-child cohort.

PubMed

Armand, Martine; Bernard, Jonathan Y; Forhan, Anne; Heude, Barbara; Charles, Marie-Aline

2017-10-21

Programming of infant development and later health may depend on early-milk polyunsaturated fatty acids (PUFA) contents, that are very variable between women for reasons not well elucidated. Indeed, a high n-6/n-3 PUFA in milk was associated with higher adiposity, arterial pressure and lower psychomotor scores in childhood. We aimed to explore the respective contribution of several maternal and perinatal factors to the variability of linoleic (LA), α-linolenic (ALA), arachidonic (AA), and docosahexaenoic (DHA) acid levels in early milk. Fatty acids of 934 colostrum samples from the EDEN mother-child cohort were analyzed by gas chromatography. The dietary intakes during the last trimester of pregnancy were estimated using a quantitative food frequency questionnaire. Relationship between milk PUFA and dietary fatty acids, and other maternal or pregnancy variables were analyzed by multiple linear regression. The means (±SD) of colostrum LA, ALA, AA and DHA levels were, respectively, 9.85 ± 1.85, 0.65 ± 0.22, 0.86 ± 0.16, and 0.64 ± 0.19% of total fatty acids. Obese mothers colostrum contained the highest level of LA and AA and the lowest level of ALA and DHA. Colostrum LA, AA and DHA levels were higher in primiparous women. Mother's age was positively associated with colostrum AA and DHA. Dietary n-6 PUFA were associated with higher LA and lower DHA levels in colostrum, while dietary n-3 PUFA were related to higher LA and lower AA levels. Contrary to what was observed for DHA, AA level in colostrum was not related to its dietary intake. High dietary AA/DHA and total n-6/n-3 ratios were critical for the content of DHA in colostrum lipids. Our study brings new insights in the understanding of the main maternal factors involved in PUFA levels variability in early milk. These data are important to consider for dietary counseling for women prior to and during pregnancy. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

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.

Evidence for differential activation of arachidonic acid metabolism in formylpeptide- and macrophage-activation-factor-stimulated guinea-pig macrophages.

PubMed Central

Homma, Y; Hashimoto, T; Nagai, Y; Takenawa, T

1985-01-01

Alterations of phospholipid and arachidonic acid metabolism were studied by treatment of guinea-pig peritoneal-exudate macrophages with chemotactic peptide, formylmethionyl-leucylphenylalanine (fMet-Leu-Phe) and macrophage activation factor (MAF). The chemotactic peptide caused a rapid rearrangement in inositol phospholipids, including a breakdown of polyphosphoinositides within 30s, followed by a resultant formation of phosphatidylinositol (PI), diacylglycerol, phosphatidic acid and non-esterified arachidonic acid within 5 min. In addition to these sequential alterations, arachidonic acid was released mainly from PI. On the other hand, MAF induced a slow liberation of arachidonic acid, mainly from phosphatidylethanolamine (PE) and phosphatidylcholine (PC) by phospholipase A2 after the incubation period of 30 min, but not any rapid changes in phospholipids. Treatment of macrophages for 15 min with fMet-Leu-Phe produced the leukotrienes (LTs) B4, C4 and D4, prostaglandins (PG) E2 and F2 alpha and thromboxane (TX) B2. In contrast, MAF could not stimulate the production of arachidonic acid metabolites during the incubation period of 15 min, but could enhance that of PGE2, PGF2 alpha, TXB2 and hydroxyeicosatetraenoic acids at 6 h. However, the stimulated formation of LTs was not detected at any time. These results indicate that the effects of fMet-Leu-Phe on both phospholipid and arachidonic acid metabolism are very different from those mediated by MAF. PMID:3931627

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

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.

Transformation of arachidonate into 6-oxoprostaglandin F1 alpha, thromboxane B2 and prostaglandin E2 by sheep lung microsomal fraction.

PubMed Central

Tai, H H; Yuan, B; Wu, A T

1978-01-01

In the presence of haemoglobin and isoproterenol, the microsomal fraction of sheep lung catalysed the conversion of arachidonate predominantly into thromboxane B2 and to a lesser extent into 6-oxoprostaglandin F1alpha. Very little prostaglandin E2 and prostaglandin F2alpha were formed. If reduced glutathione was added in combination with haemoglobin and isoproterenol, the synthesis of prostaglandin E2 was favoured over that of thromboxane B2 and 6-oxoprostaglandin F1alpha. The identities of these products were confirmed by t.l.c. and by combined g.l.c.-mass spectrometry. These results indicate that microsomal fraction of sheep lung possesses active prostaglandin synthase, prostacyclin synthase and thromboxane synthase activities. PMID:637853

DIFFERENCES IN ARACHIDONIC ACID METABOLISM BY HUMAN MYELOMONCYTIC CELL LINES

EPA Science Inventory

The production of arachidonic acid metabolites by the HL60, ML3, and U937 human phagocyte cell lines were determined after incubation with interferongamma (IFNg; 500 U/ml) or vehicle for 4 days. ells were prelabeled with tritiated arachidonic acid for 4 hours, and media supernata...

Intakes of omega-3 polyunsaturated fatty acids and blood pressure change over time: Possible interaction with genes involved in 20-HETE and EETs metabolism.

PubMed

Tagetti, Angela; Ericson, Ulrika; Montagnana, Martina; Danese, Elisa; Almgren, Peter; Nilsson, Peter; Engström, Gunnar; Hedblad, Bo; Minuz, Pietro; Orho-Melander, Marju; Fava, Cristiano; Melander, Olle

2015-07-01

A high intake of omega-3 polyunsaturated fatty acids (ω-3 PUFAs), has been associated with reduced levels of blood pressure (BP). Their antihypertensive action may be due to the reduction of the ω-6/ω-3 ratio and the resulting competitive effect of ω-3 as compared to arachidonic acid (an ω-6 PUFA) as a substrate of cytochrome P450 (CYP450) enzymes involved in the production of vasoactive mediators. Some functional polymorphisms (SNPs), in genes which encode for the same enzymes, were associated with hypertension and ischemic stroke in the Malmö Diet and Cancer (MDC), a Swedish urban-based longitudinal study. The aim of this study was to evaluate the effect of the intake of different types of PUFAs on BP change over time (Δ-BP; mean follow-up 16.6±1.5 years; n=3.550 with complete phenotypic data), also considering the interaction with SNPs in genes involved in their metabolism via CYP450. PUFA intakes were collected by a modified diet history method, and functional SNPs in CYP4F2, CYP4A11, CYP2J2 and EPHX2 were genotyped by Taqman. We did not find any overall association between ω-6 and ω-3 PUFA intakes, or their ratio, with Δ-BP but observed an interaction between CYP4F2 V433M genotype and total omega-3, α-linolenic acid and linoleic/α-linolenic ratio, so that a higher ω-3 PUFA intake was significantly associated with a more pronounced BP decrease over time in subjects with the 433VV genotype (-0.041±0.018 mmHg/year; p=0.024; p-interaction=0.031) CONCLUSIONS: Our data do not support a major role of ω-6 or ω-3 PUFA intakes on BP change over time, but suggest a possible interaction of ω-3 PUFA with the CYP4F2 V433M. Copyright © 2015 Elsevier Inc. All rights reserved.

Erythrocyte polyunsaturated fatty acid composition is associated with depression and FADS genotype in Caucasians.

PubMed

Cribb, Lachlan; Murphy, Jenifer; Froud, Amy; Oliver, Georgina; Bousman, Chad A; Ng, Chee H; Sarris, Jerome

2017-05-29

Polyunsaturated fatty acids (PUFAs) play an important role in the pathophysiology of major depressive disorder (MDD), related, in part, to their role in inflammatory systems. The enzymes δ-5 and δ-6 desaturase are the rate-limiting steps in the metabolism of PUFAs and are encoded in the genes fatty acid desaturase (FADS) 1 and 2, respectively. Single nucleotide polymorphisms (SNPs) and haplotypes within the FADS gene cluster have been shown to influence PUFA composition. The objective of this study was to determine whether key omega-3 (n-3) and omega-6 (n-6) fatty acids may be associated with depression, and to explore the role of FADS genotype in PUFA variation. Four erythrocyte long chain (LC) fatty acids (linoleic acid [LA], α-linolenic acid [ALA], arachidonic acid [AA] and Eicosapentaenoic acid [EPA]), as well as six SNPs (rs174537, rs174547, rs174570, rs174575, rs498793 and rs3834458) within the FADS gene cluster were measured in a sample of 207 participants (154 with MDD versus 53 non-depressed controls). The precursor LC-PUFAs LA and ALA appeared to be negatively associated with depression (P < 0.001 and P < 0.01, respectively), while AA:LA (surrogate measure of desaturase activity) was positively associated with depression (P < 0.01). No significant differences were noted in erythrocyte EPA, AA or AA:EPA between groups. Minor alleles of each SNP (excluding rs498793) were associated with variation in desaturase activity and LA. Both rs174537 and rs174547 were associated with ALA. No genotype was associated with EPA or AA. Minor alleles of rs174537 and rs174547 were significantly associated with lower odds of MDD (although significance was lost after correction for multiple comparisons). Precursor LC-PUFAs, LA and ALA, appear to be associated with MDD and potentially modulated by genetic variation in the FADS gene cluster. These results provide support for the consideration of PUFA composition, diet and FADS genetic variation in the

Deuterated polyunsaturated fatty acids reduce brain lipid peroxidation and hippocampal amyloid β-peptide levels, without discernable behavioral effects in an APP/PS1 mutant transgenic mouse model of Alzheimer's disease.

PubMed

Raefsky, Sophia M; Furman, Ran; Milne, Ginger; Pollock, Erik; Axelsen, Paul; Mattson, Mark P; Shchepinov, Mikhail S

2018-06-01

Alzheimer's disease (AD) involves progressive deposition of amyloid β-peptide (Aβ), synapse loss, and neuronal death, which occur in brain regions critical for learning and memory. Considerable evidence suggests that lipid peroxidation contributes to synaptic dysfunction and neuronal degeneration, both upstream and downstream of Aβ pathology. Recent findings suggest that lipid peroxidation can be inhibited by replacement of polyunsaturated fatty acids (PUFA) with isotope-reinforced (deuterated) PUFA (D-PUFA), and that D-PUFA can protect neurons in experimental models of Parkinson's disease. Here, we determined whether dietary D-PUFA would ameliorate Aβ pathology and/or cognitive deficits in a mouse model of AD (amyloid precursor protein/presenilin 1 double mutant transgenic mice). The D-PUFA diet did not ameliorate spatial learning and memory deficits in the AD mice. Compared to mice fed an hydrogenated-PUFA control diet, those fed D-PUFA for 5 months exhibited high levels of incorporation of deuterium into arachidonic acid and docosahexaenoic acid, and reduced concentrations of lipid peroxidation products (F2 isoprostanes and neuroprostanes), in the brain tissues. Concentrations of Aβ40 and Aβ38 in the hippocampus were significantly lower, with a trend to reduced concentrations of Aβ42, in mice fed D-PUFA compared to those fed hydrogenated-PUFA. We conclude that a D-PUFA diet reduces the brain tissue concentrations of both arachidonic acid and docosahexaenoic acid oxidation products, as well as the concentration of Aβs. Published by Elsevier Inc.

Chemical composition and nutritional quality of sea cucumbers.

PubMed

Wen, Jing; Hu, Chaoqun; Fan, Sigang

2010-11-01

The dried form of sea cucumbers has been a seafood and medicinal cure for Asians over many centuries. In this study the chemical composition and nutritional quality of eight common sea cucumbers (Stichopus herrmanni, Thelenota ananas, Thelenota anax, Holothuria fuscogilva, Holothuria fuscopunctata, Actinopyga mauritiana, Actinopyga caerulea and Bohadschia argus) were determined. All species except T. anax and A. caerulea had higher protein and lower fat levels. A. mauritiana and B. argus had less ash content. Glycine was the dominant amino acid found in all species, and content ranged from 126 to 216 mg g(-1) of crude protein. All species exhibited low lysine:arginine ratio and higher essential amino acid scores were obtained by threonine and phenylalanine + tyrosine. A. mauritiana had proportionally less saturated fatty acids (31.23%), and more monounsaturated fatty acids (45.64%) and polyunsaturated fatty acids (PUFA, 23.13%) than other species. Arachidonic acid (C20:4n-6) was the major PUFA in all species. T. ananas, A. mauritiana and A. caerulea contained more n-3 PUFA. The n-3/n-6 ratios of eight sea cucumbers species ranged from 0.25 to 0.61. Sea cucumbers are a seafood with high protein and low fat levels. The amino acid contents were similar but fatty acid profiles were different among species. The comparison showed that T. ananas, A. mauritiana and B. argus possessed higher nutritional values than other sea cucumber species. 2010 Society of Chemical Industry