Kumar, Aishwarya; Mastana, Sarabjit S; Lindley, Martin R
Asthma is one of the most common and prevalent problems worldwide affecting over 300 million individuals. There is some evidence from observational and intervention studies to suggest a beneficial effect of n-3 PUFA in inflammatory diseases, specifically asthma. Marine-based n-3 PUFA have therefore been proposed as a possible complementary/alternative therapy for asthma. The proposed anti-inflammatory effects of n-3 fatty acids may be linked to a change in cell membrane composition. This altered membrane composition following n-3 fatty acid supplementation (primarily EPA and DHA) can modify lipid mediator generation via the production of eicosanoids with a reduced inflammatory potential/impact. A recently identified group of lipid mediators derived from EPA including E-series resolvins are proposed to be important in the resolution of inflammation. Reduced inflammation attenuates the severity of asthma including symptoms (dyspnoea) and exerts a bronchodilatory effect. There have been no major health side effects reported with the dietary supplementation of n-3 fatty acids or their mediators; consequently supplementing with n-3 fatty acids is an attractive non-pharmacological intervention which may benefit asthma.
We have reviewed literature regarding the effects of n-3 polyunsaturated fatty acids (PUFA) on risk factors for atherosclerosis in human subjects. Dietary intervention with long chain n-3 PUFA decreased some risk factor (s) for atherosclerosis in most human studies reviewed. These benefits resulted ...
Crupi, R; Marino, A; Cuzzocrea, S
Omega-3 polyunsaturated fatty acids (PUFA) are essential unsaturated fatty acids with a double bond (C=C) starting after the third carbon atom from the end of the carbon chain. They are important nutrients but, unfortunately, mammals cannot synthesize them, whereby they must be obtained from food sources or from supplements. Amongst nutritionally important polyunsaturated n-3 fatty acids, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are highly concentrated in the brain and have anti-oxidative stress, anti-inflammatory and antiapoptotic effects. They are involved in many bodily processes and may reportedly lead to neuron protection in neurological diseases. aged or damaged neurons and in Alzheimer's disease. Their effect in cognitive and behavioral functions and in several neurological and psychiatric disorders has been also proven. The dentate gyrus (DG), a sub-region of hippocampus, is implicated in cognition and mood regulation. The hippocampus represents one of the two areas in the mammalian brain in which adult neurogenesis occurs. This process is associated with beneficial effects on cognition, mood and chronic pharmacological treatment. The exposure to n-3 fatty acids enhances adult hippocampal neurogenesis associated with cognitive and behavioral processes, promotes synaptic plasticity by increasing long-term potentiation and modulates synaptic protein expression to stimulate the dendritic arborization and new spines formation. On this basis we review the effect of n-3 fatty acids on adult hippocampal neurogenesis and neuroplasticity. Moreover their possible use as a new therapeutic approach for neurodegenerative diseases is pointed out.
N-3 polyunsaturated fatty acids (PUFAs) including α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory effects and neuronal protective functions and may benefit prevention of dementia; however, the epidemiological evidence is very limited. Therefore, the literature about the association between n-3 PUFA and dementia was searched, by using Pubmed. In the analyses of observational studies, n-3 PUFA has been reported to be beneficially associated with dementia in 17 studies; however, the beneficial association between n-3 PUFA and dementia was denied by three studies. In the analyses of intervention studies, n-3 PUFA supplementation was beneficially associated with dementia in eight studies; however, five studies reported the negligible effect of n-3 PUFA for dementia. N-3 PUFA may improve Alzheimer's disease by increasing clearance of amyloid-β peptide, neurotrophic and neuroprotective factors, and by anti-inflammatory effects. In conclusion, patients with mild memory and/or cognitive impairment can be treated by a long-term and higher intake of n-3 PUFA.
N-3 polyunsaturated fatty acids (PUFAs) including α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory effects and neuronal protective functions and may benefit prevention of dementia; however, the epidemiological evidence is very limited. Therefore, the literature about the association between n-3 PUFA and dementia was searched, by using Pubmed. In the analyses of observational studies, n-3 PUFA has been reported to be beneficially associated with dementia in 17 studies; however, the beneficial association between n-3 PUFA and dementia was denied by three studies. In the analyses of intervention studies, n-3 PUFA supplementation was beneficially associated with dementia in eight studies; however, five studies reported the negligible effect of n-3 PUFA for dementia. N-3 PUFA may improve Alzheimer’s disease by increasing clearance of amyloid-β peptide, neurotrophic and neuroprotective factors, and by anti-inflammatory effects. In conclusion, patients with mild memory and/or cognitive impairment can be treated by a long-term and higher intake of n-3 PUFA. PMID:27924168
N-3 Polyunsaturated fatty acids have been shown to have potential beneficial effects for chronic diseases including cancer, insulin resistance and cardiovascular disease. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in particular have been studied extensively, whereas substantive evidence for a biological role for the precursor, alpha-linolenic acid (ALA), is lacking. It is not enough to assume that ALA exerts effects through conversion to EPA and DHA, as the process is highly inefficient in humans. Thus, clarification of ALA's involvement in health and disease is essential, as it is the principle n-3 polyunsaturated fatty acid consumed in the North American diet and intakes of EPA and DHA are typically very low. There is evidence suggesting that ALA, EPA and DHA have specific and potentially independent effects on chronic disease. Therefore, this review will assess our current understanding of the differential effects of ALA, EPA and DHA on cancer, insulin resistance, and cardiovascular disease. Potential mechanisms of action will also be reviewed. Overall, a better understanding of the individual role for ALA, EPA and DHA is needed in order to make appropriate dietary recommendations regarding n-3 polyunsaturated fatty acid consumption. PMID:19664246
Intake of marine-based n-3 fatty acids (EPA, docosapentaenoic acid and DHA) is recommended to prevent CHD. Stearidonic acid (SDA), a plant-based n-3 fatty acid, is a precursor of EPA and may be more readily converted to EPA than a-linolenic acid (ALA). While transgenic soyabeans might supply SDA at ...
Dugan, Michael E.R.; Vahmani, Payam; Turner, Tyler D.; Mapiye, Cletos; Juárez, Manuel; Prieto, Nuria; Beaulieu, Angela D.; Zijlstra, Ruurd T.; Patience, John F.; Aalhus, Jennifer L.
Pork is the most widely eaten meat in the world, but typical feeding practices give it a high omega-6 (n-6) to omega-3 (n-3) fatty acid ratio and make it a poor source of n-3 fatty acids. Feeding pigs n-3 fatty acids can increase their contents in pork, and in countries where label claims are permitted, claims can be met with limited feeding of n-3 fatty acid enrich feedstuffs, provided contributions of both fat and muscle are included in pork servings. Pork enriched with n-3 fatty acids is, however, not widely available. Producing and marketing n-3 fatty acid enriched pork requires regulatory approval, development costs, quality control costs, may increase production costs, and enriched pork has to be tracked to retail and sold for a premium. Mandatory labelling of the n-6/n-3 ratio and the n-3 fatty acid content of pork may help drive production of n-3 fatty acid enriched pork, and open the door to population-based disease prevention polices (i.e., food tax to provide incentives to improve production practices). A shift from the status-quo, however, will require stronger signals along the value chain indicating production of n-3 fatty acid enriched pork is an industry priority. PMID:26694475
Jenssen, Trond; Hartmann, Anders; Diep, Lien M.; Dahle, Dag O.; Reisæter, Anna V.; Bjerve, Kristian S.; Christensen, Jeppe H.; Schmidt, Erik B.; Svensson, My
Background and objectives Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants. Design, setting, participants, & measurements In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation. Results There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels (≥7.95 weight percentage) compared with low levels (<7.95 weight percentage) for all age categories (pooled mortality rate ratio estimate, 0.69; 95% confidence interval, 0.57 to 0.85). When divided into quartiles according to marine n-3 polyunsaturated fatty acid levels, patients in the upper quartile compared with the lower quartile had a 56% lower risk of death (adjusted hazard ratio, 0.44; 95% confidence interval, 0.26 to 0.75) using multivariable Cox proportional hazard regression analysis. There was a lower hazard ratio for death from cardiovascular disease with high levels of marine n-3 polyunsaturated fatty acid and a lower hazard ratio for death from infectious disease with high levels of the marine n-3 polyunsaturated fatty acid eicosapentaenoic acid, whereas there was no association between total or individual marine n-3 polyunsaturated fatty acid levels and cancer mortality. Conclusions Higher plasma phospholipid marine n-3
Faris, Richard J; Boddicker, Rebecca L; Walker-Daniels, Jennifer; Li, Jenny; Jones, Douglas E; Spurlock, Michael E
Fatty acids have distinct cellular effects related to inflammation and insulin sensitivity. Dietary saturated fat activates toll-like receptor 4, which in turn can lead to chronic inflammation, insulin resistance, and adipose tissue macrophage infiltration. Conversely, n3 fatty acids are generally antiinflammatory and promote insulin sensitivity, in part via peroxisome proliferator-activated receptor γ. Ossabaw swine are a useful biomedical model of obesity. We fed Ossabaw pigs either a low-fat control diet or a diet containing high-fat palm oil with or without additional n3 fatty acids for 30 wk to investigate the effect of saturated fats and n3 fatty acids on obesity-linked inflammatory markers. The diet did not influence the inflammatory markers C-reactive protein, TNFα, IL6, or IL12. In addition, n3 fatty acids attenuated the increase in inflammatory adipose tissue CD16–CD14+ macrophages induced by high palm oil. High-fat diets with and without n3 fatty acids both induced hyperglycemia without hyperinsulinemia. The high-fat only group but not the high-fat group with n3 fatty acids showed reduced insulin sensitivity in response to insulin challenge. This effect was not mediated by decreased phosphorylation of protein kinase B. Therefore, in obese Ossabaw swine, n3 fatty acids partially attenuate insulin resistance but only marginally change inflammatory status and macrophage phenotype in adipose tissue. PMID:23561883
The first evidence that fish oil fatty acids might have a beneficial effect on coronary heart disease came from the discovery that Greenland Eskimos, who have a diet high in n-3 fatty acids, have a lower mortality from coronary heart disease than do Danes and Americans. Long-chain polyunsaturated fatty acids are essential in our diets and can be classified in 2 groups: n-6 fatty acids found in plant seeds and n-3 fatty acids found in marine vertebrates. Further evidence of n-3 benefits to human health include a 1989 study demonstrating a 29% reduction in fatal cardiac arrhythmias among subjects with a recent myocardial infarction who had been advised to consume fish oil. The GISSI-Prevenzione Trial found a significant reduction in relative reduction of death, cardiac death, nonfatal myocardial infarction, and stroke in subjects consuming n-3 fatty acids. In a recent study, subjects with implanted cardiac defibrillators (ICDs) at high risk for fatal ventricular arrhythmias were randomly assigned to four 1-g capsules of either an ethyl ester concentrate of n-3 fatty acids or olive oil daily for 12 mo. Subjects receiving n-3 who thus had significantly higher levels of eicosapentaenoic acid and docosahexaenoic acid in their red blood cell membranes showed a longer time to first ICD events and had a significantly lower relative risk of having an ICD event or probable event (P = 0.033). These studies demonstrate that fish oil fatty acids have beneficial effects on coronary heart disease.
Previous animal studies demonstrated that chronic feeding of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFA) that modifies muscle membrane fatty acid composition promotes protein anabolism by blunting the age-associated deterioration in insulin sensitivity. The current study assessed, as a pr...
Olsen, S F; Hansen, H S; Secher, N J; Jensen, B; Sandström, B
It has been hypothesized that marine n-3 fatty acids ingested during pregnancy prolong duration of pregnancy and increase fetal growth rate in humans. By a combined self-administered questionnaire and interview applied in the 30th week of gestation we assessed dietary intake of marine n-3 fatty acids and energy in a population-based sample of 965 pregnant Danish women; in a random 14% subsample we also measured marine n-3 fatty acids relative to arachidonic acid (FA-ratio) in erythrocytes. Mean intake of marine n-3 fatty acids was 0.25 (95% range 0-0.75) g/d. We could detect no association between n-3 fatty acid intake and FA-ratio on the one hand, and gestation length, birth weight and birth length on the other. The analyses were adjusted for maternal height, prepregnant weight, parity and smoking. The conclusion from the study was that within the intake range of this population, marine n-3 fatty acids ingested in the weeks prior to the 30th week of pregnancy seem not to be a predictor of gestation length or fetal growth rate.
Zhao, Yadong; Wang, Miao; Lindström, Mikael E; Li, Jiebing
In order to establish Ciona intestinalis as a new bioresource for n-3 fatty acids-rich marine lipids, the animal was fractionated into tunic and inner body tissues prior to lipid extraction. The lipids obtained were further classified into neutral lipids (NL), glycolipids (GL) and phospholipids (PL) followed by qualitative and quantitative analysis using GC-FID, GC-MS, (1)H NMR, 2D NMR, MALDI-TOF-MS and LC-ESI-MS methods. It was found that the tunic and inner body tissues contained 3.42-4.08% and 15.9-23.4% of lipids respectively. PL was the dominant lipid class (42-60%) irrespective of the anatomic fractions. From all lipid fractions and classes, the major fatty acids were 16:0, 18:1n-9, C20:1n-9, C20:5n-3 (EPA) and C22:6n-3 (DHA). The highest amounts of long chain n-3 fatty acids, mainly EPA and DHA, were located in PL from both body fractions. Cholestanol and cholesterol were the dominant sterols together with noticeable amounts of stellasterol, 22 (Z)-dehydrocholesterol and lathosterol. Several other identified and two yet unidentified sterols were observed for the first time from C. intestinalis. Different molecular species of phosphatidylcholine (34 species), sphingomyelin (2 species), phosphatidylethanolamine (2 species), phosphatidylserine (10 species), phosphatidylglycerol (9 species), ceramide (38 species) and lysophospholipid (5 species) were identified, representing the most systematic PL profiling knowledge so far for the animal. It could be concluded that C. intestinalis lipids should be a good alternative for fish oil with high contents of n-3 fatty acids. The lipids would be more bioavailable due to the presence of the fatty acids being mainly in the form of PL.
Fedorova, Irina; Hussein, Nahed; Di Martino, Carmine; Moriguchi, Toru; Hoshiba, Junji; Majchrzak, Sharon; Salem, Norman
Deficiency in n-3 fatty acids has been accomplished through the use of an artificial rearing method in which ICR mouse pups were hand fed a deficient diet starting from the second day of life. There was a 51% loss of total brain DHA in mice with an n-3 fatty acid deficient diet relative to those with a diet sufficient in n-3 fatty acids. N-3 fatty acid adequate and deficient mice did not differ in terms of locomotor activity in the open field test or in anxiety-related behavior in the elevated plus maze. The n-3 fatty acid deficient mice demonstrated impaired learning in the reference-memory version of the Barnes circular maze as they spent more time and made more errors in search of an escape tunnel. No difference in performance between all dietary groups in the cued and working memory version of the Barnes maze was observed. This indicated that motivational, motor and sensory factors did not contribute to the reference memory impairment. PMID:18037280
Tanaka, Hideko; Harauma, Akiko; Takimoto, Mao; Moriguchi, Toru
In our previously study, we reported lower tear volume in with an n-3 fatty acid deficient mice and that the docosahexaenoic acid and total n-3 fatty acid levels in these mice are significantly reduced in the meibomian gland, which secretes an oily tear product. Furthermore, we noted very long chain fatty acids (≥25 carbons) in the meibomian gland. To verify the detailed mechanism of the low tear volume in the n-3 fatty acid-deficient mice, we identified the very long chain fatty acids in the meibomian gland, measured the fatty acid composition in the tear product. Very long chain fatty acids were found to exist as monoesters. In particular, very long chain fatty acids with 25-29 carbons existed for the most part as iso or anteiso branched-chain fatty acids. n-3 fatty acid deficiency was decreased the amount of meibum secretion from meibomian gland without change of fatty acid composition. These results suggest that the n-3 fatty acid deficiency causes the enhancement of evaporation of tear film by reducing oily tear secretion along with the decrease of meibomian gland function.
Siddiqui, Rafat A; Harvey, Kevin A; Zaloga, Gary P
Epidemiological evidence from Greenland Eskimos and Japanese fishing villages suggests that eating fish oil and marine animals can prevent coronary heart disease. Dietary studies from various laboratories have similarly indicated that regular fish oil intake affects several humoral and cellular factors involved in atherogenesis and may prevent atherosclerosis, arrhythmia, thrombosis, cardiac hypertrophy and sudden cardiac death. The beneficial effects of fish oil are attributed to their n-3 polyunsaturated fatty acid (PUFA; also known as omega-3 fatty acids) content, particularly eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Dietary supplementation of DHA and EPA influences the fatty acid composition of plasma phospholipids that, in turn, may affect cardiac cell functions in vivo. Recent studies have demonstrated that long-chain omega-3 fatty acids may exert beneficial effects by affecting a wide variety of cellular signaling mechanisms. Pathways involved in calcium homeostasis in the heart may be of particular importance. L-type calcium channels, the Na+-Ca2+ exchanger and mobilization of calcium from intracellular stores are the most obvious key signaling pathways affecting the cardiovascular system; however, recent studies now suggest that other signaling pathways involving activation of phospholipases, synthesis of eicosanoids, regulation of receptor-associated enzymes and protein kinases also play very important roles in mediating n-3 PUFA effects on cardiovascular health. This review is therefore focused on the molecular targets and signaling pathways that are regulated by n-3 PUFAs in relation to their cardioprotective effects.
Barden, Anne; O'Callaghan, Nathan; Burke, Valerie; Mas, Emile; Beilin, Lawrence J; Fenech, Michael; Irish, Ashley B; Watts, Gerald F; Puddey, Ian B; Huang, Rae-Chi; Mori, Trevor A
DNA telomere shortening associates with the age-related increase cardiovascular disease (CVD) risk. Reducing oxidative stress, could modify telomere erosion during cell replication, and CVD risk in patients with chronic kidney disease (CKD). The effect of n-3 fatty acids and coenzyme Q10 (CoQ) on telomere length was studied in a double-blind placebo-controlled trial in CKD. Eighty-five CKD patients were randomized to: n-3 fatty acids (4 g); CoQ (200 mg); both supplements; or control (4 g olive oil), daily for 8 weeks. Telomere length was measured in neutrophils and peripheral blood mononuclear cells (PBMC) at baseline and 8 weeks, with and without correction for cell counts. Main and interactive effects of n-3 fatty acids and CoQ on telomere length were assessed adjusting for baseline values. F₂-isoprostanes were measured as markers of oxidative stress. There was no effect of n-3 fatty acids or CoQ on neutrophil or PBMC telomere length. However, telomere length corrected for neutrophil count was increased after n-3 fatty acids (p = 0.015). Post-intervention plasma F₂-isoprostanes were negative predictors of post-intervention telomere length corrected for neutrophil count (p = 0.025).The effect of n-3 fatty acids to increased telomere length corrected for neutrophil count may relate to reduced oxidative stress and increased clearance of neutrophils with shorter telomeres from the circulation. This may be a novel mechanism of modifying CVD risk in CKD patients.
Araújo, Maria Elisa Melo Branco de; Campos, Paula Renata Bueno; Alberto, Thiago Grando; Contesini, Fabiano Jares; Carvalho, Patrícia de Oliveira
The search for new biocatalysts has aroused great interest due to the variety of micro-organisms and their role as enzyme producers. Native lipases from Aspergillus niger and Rhizopus javanicus were used to enrich the n-3 long-chain polyunsaturated fatty acids content in the triacylglycerols of soybean oil by acidolysis with free fatty acids from sardine oil in solvent-free media. For the immobilization process, the best lipase/support ratios were 1:3 (w/w) for Aspergillus niger lipase and 1:5 (w/w) for Rhizopus javanicus lipase using Amberlite MB-1. Both lipases maintained constant activity for 6 months at 4°C. Reaction time, sardine-free fatty acids:soybean oil mole ratio and initial water content of the lipase were investigated to determine their effects on n-3 long-chain polyunsaturated fatty acids incorporation into soybean oil. Structured triacylglycerols with 11.7 and 7.2% of eicosapentaenoic acid+docosahexaenoic acid were obtained using Aspergillus niger lipase and Rhizopus javanicus lipase, decreasing the n-6/n-3 fatty acids ratio of soybean oil (11:1 to 3.5:1 and 4.7:1, respectively). The best reaction conditions were: initial water content of lipase of 0.86% (w/w), sardine-free faty acids:soybean oil mole ratio of 3:1 and reaction time of 36h, at 40°C. The significant factors for the acidolysis reaction were the sardine-free fatty acids:soybean oil mole ratio and reaction time. The characterization of structured triacylglycerols was obtained using easy ambient sonic-spray ionization mass spectrometry. The enzymatic reaction led to the formation of many structured triacylglycerols containing eicosapentaenoic acid, docosahexaenoic acid or both polyunsaturated fatty acids.
Barceló-Coblijn, Gwendolyn; Murphy, Eric J
There is little doubt regarding the essential nature of alpha-linolenic acid (ALA), yet the capacity of dietary ALA to maintain adequate tissue levels of long chain n-3 fatty acids remains quite controversial. This simple point remains highly debated despite evidence that removal of dietary ALA promotes n-3 fatty acid inadequacy, including that of docosahexaenoic acid (DHA), and that many experiments demonstrate that dietary inclusion of ALA raises n-3 tissue fatty acid content, including DHA. Herein we propose, based upon our previous work and that of others, that ALA is elongated and desaturated in a tissue-dependent manner. One important concept is to recognize that ALA, like many other fatty acids, rapidly undergoes beta-oxidation and that the carbons are conserved and reused for synthesis of other products including cholesterol and fatty acids. This process and the differences between utilization of dietary DHA or liver-derived DHA as compared to ALA have led to the dogma that ALA is not a useful fatty acid for maintaining tissue long chain n-3 fatty acids, including DHA. Herein, we propose that indeed dietary ALA is a crucial dietary source of n-3 fatty acids and its dietary inclusion is critical for maintaining tissue long chain n-3 levels.
Lahoz, C; Mata, P
The effects of n-3 polyunsaturated fatty acid (n-3 PFA) intake on lipoprotein metabolism, eicosanoid metabolism, coagulation and the fibrinolytic system, mediators of inflammation, and blood pressure are discussed. The possible role such effects may have on the process of atherogenesis is examined. Laboratory animal studies with n-3 PFA supplements are reviewed. Finally, a review of clinical and epidemiological studies in human subjects is made in order to evaluate whether the experimental findings have clinical relevance. The conclusion is that, at the present time, there is insufficient support for the use of n-3 PFA supplements either in prophylaxis or in treating ischemic cardiopathy.
Garcia, H S; Arcos, J A; Ward, D J; Hill, C G
Menhaden oil, a rich source of n-3 fatty acids, was interesterified with conjugated linoleic acid (CLA) in a reaction medium composed solely of substrates and either free or immobilized commercial lipase preparations. Of five lipases tested, an immobilized preparation from Mucor miehei provided the fastest rate of incorporation of CLA into fish oil acylglycerols; however, and as observed with most of the lipases utilized, a significant proportion of the n-3 fatty acid residues were liberated in the process. A soluble lipase from Candida rugosa converted free CLA to acylglycerol residues while leaving the n-3 fatty acid residues virtually untouched. Even though the reaction rate was slower for this enzyme than for the other four lipase preparations, the specificity of the free C. rugosa lipase gives it the greatest potential for commercial use in preparing fish oils enriched in CLA residues but still retaining their original n-3 fatty acid residues.
Ounnas, Fayçal; de Lorgeril, Michel; Salen, Patricia; Laporte, François; Calani, Luca; Mena, Pedro; Brighenti, Furio; Del Rio, Daniele; Demeilliers, Christine
As long-chain fatty acids (LCFA) of the n-3 series are critically important for human health, fish consumption has considerably increased in recent decades, resulting in overfishing to respond to the worldwide demand, to an extent that is not sustainable for consumers' health, fisheries economy, and marine ecology. In a recent study, it has been shown that whole rye (WR) consumption improves blood and liver n-3 LCFA levels and gut microbiota composition in rats compared to refined rye. The present work demonstrates that specific colonic polyphenol metabolites may dose dependently stimulate the synthesis of n-3 LCFA, possibly through their microbial and hepatic metabolites in rats. The intake of plant n-3 alpha-linolenic acid and WR results in a sort of fatty fish-like effect, demonstrating that the n-3 LCFA levels in blood and tissues could be increased without eating marine foods, and therefore without promoting unsustainable overfishing, and without damaging marine ecology.
Ounnas, Fayçal; de Lorgeril, Michel; Salen, Patricia; Laporte, François; Calani, Luca; Mena, Pedro; Brighenti, Furio; Del Rio, Daniele; Demeilliers, Christine
As long-chain fatty acids (LCFA) of the n-3 series are critically important for human health, fish consumption has considerably increased in recent decades, resulting in overfishing to respond to the worldwide demand, to an extent that is not sustainable for consumers’ health, fisheries economy, and marine ecology. In a recent study, it has been shown that whole rye (WR) consumption improves blood and liver n-3 LCFA levels and gut microbiota composition in rats compared to refined rye. The present work demonstrates that specific colonic polyphenol metabolites may dose dependently stimulate the synthesis of n-3 LCFA, possibly through their microbial and hepatic metabolites in rats. The intake of plant n-3 alpha-linolenic acid and WR results in a sort of fatty fish-like effect, demonstrating that the n-3 LCFA levels in blood and tissues could be increased without eating marine foods, and therefore without promoting unsustainable overfishing, and without damaging marine ecology. PMID:28071699
Novak, Elizabeth M; Innis, Sheila M
Levels of n-6, n-3, and medium-chain fatty acids (MCFA) in milk are highly variable. Higher carbohydrate intakes are associated with increased mammary gland MCFA synthesis, but the role of unsaturated fatty acids for milk MCFA secretion is unclear. This study addressed whether n-6 and n-3 fatty acids, which are known to inhibit hepatic fatty acid synthesis, influence MCFA in rat and human milk and the implications of varying MCFA, n-6, and n-3 fatty acids in rat milk for metabolic regulation in the neonatal liver. Rats were fed a low-fat diet or one of six higher-fat diets, varying in 16:0, 18:1n-9, 18:2n-6, 18:3n-3, and long-chain (LC) n-3 fatty acids. Higher maternal dietary 18:2n-6 or 18:3n-3 did not influence milk MCFA, but lower maternal plasma triglycerides, due to either a low-fat or a high-fat high-LC n-3 diet led to higher milk MCFA. MCFA levels were inversely associated with 18:1n-9, 18:2n-6, and 18:3n-3 in human milk, likely reflecting the association between dietary total fat and unsaturated fatty acids. High LC n-3 fatty acid in rat milk was associated with lower hepatic Pklr, Acly, Fasn, and Scd1 and higher Hmgcs2 in the milk-fed rat neonate, with no effect of milk 18:1n-9, 18:2n-6, or MCFA. These studies show that the dietary fatty acid composition does not impact MCFA secretion in milk, but the fatty acid composition of milk, particularly the LC n-3 fatty acid, is relevant to hepatic metabolic regulation in the milk-fed neonate.
Glück, Tobias; Rupp, Heinz; Alter, Peter
Due to ambiguous findings on cardiovascular benefits of systemic omega-3 fatty acid therapy, endogenous mechanisms contributing to local organ-specific concentrations of highly unsaturated fatty acids (HUFA) were examined. Using gas chromatography, 43 fatty acids were analyzed in atrial and ventricular myocardium and in pericardial fluid of male Wistar rats. To examine the endogenous fatty acid metabolism, precursors were administered into the pericardial sac. Pro- and anti-inflammatory actions were induced by talc or fenofibrate, respectively. Physical exercise and a sedentary obese state were used for increased beta-oxidation. DHA (22:6n-3) was increased in ventricular when compared with atrial myocardium (9.0 ± 2.1% vs. 4.7 ± 1.0%, p < 0.001). Intrapericardial EPA (20:5n-3) application lead to an increase of the succeeding tetracosapentaenoic acid (24:5n-3) in atrial myocardium, which is a key precursor of DHA. In contrast, proinflammatory stimulation of the n-6 HUFA pathway did not influence the n-3 metabolism. Exercise- and obesity-induced increased beta-oxidation, the finalizing step of DHA synthesis, was associated with increased ventricular DHA concentrations (6.7 ± 1.0% vs. 8.4 ± 1.2%, p < 0.01). It is concluded that the endogenous metabolism contributes markedly to myocardial HUFA concentrations. The findings are supposed to influence the efficacy of oral HUFA treatment and provide a rationale for divergent findings of previous trials on omega-3 therapy.
Cunnane, S C; McAdoo, K R; Horrobin, D F
1. Lean (ln/ln) and obese (ob/ob) mice were given diets containing a fat source of 100 g evening primrose (Oenothera biennis) oil (fatty acids 18:2n-6, 18:3n-6; EPO) or 100 g cod liver oil (20:5n-3, 22:6n-3; CLO)/kg diet. 2. Weight gain was lower in the ob/ob mice fed on CLO, an effect unrelated to food intake. 3. In the ob/ob mice fed on CLO, thromboxane synthesis by clotting platelets was reduced compared with that in ob/ob mice fed on EPO. 4. The ob/ob CLO-fed mice had lower arachidonic acid but higher levels of n-3 fatty acids in liver, brown adipose tissue and white adipose tissue. 5. The n-3 fatty acids in CLO therefore replaced the n-6 fatty acids in tissue lipids and reduced synthesis of '2 series' prostaglandins in addition to causing lower weight gain in the CLO-fed ob/ob mice.
Stephensen, Charles B
Eating fish or taking n-3 fatty acid supplements can decrease the risk and severity of cardiovascular disease. Such supplements also provide symptomatic relief for rheumatoid arthritis patients. Recent research suggests that asthma, another highly prevalent, chronic inflammatory disease, may also respond to fish oil supplements.
Lewis, N M; Seburg, S; Flanagan, N L
Dietary intake of omega-3 fatty acids (n-3 PUFA) decreases the risk of heart disease, inhibits the growth of prostate and breast cancer, delays the loss of immunological functions, and is required for normal fetal brain and visual development. The US has not established a recommended daily intake for n-3 PUFA. However, Canada has established the Canadian Recommended Nutrient Intake (CRNI) at 0.5% of energy. Dietary sources of n-3 PUFA include fish, chicken, eggs, canola oil, and soybean oil. Food consumption studies in the US indicate that the majority of Americans do not meet the CRNI for n-3 PUFA. Mean n-3 PUFA consumption was 78% of the CRNI for Midwestern women during pregnancy. In Midwestern women at risk for breast cancer, the mean n-3 PUFA consumption is approximately 50% of the CRNI. Increased consumption of n-3 PUFA requires identification of a food source that the public would eat in sufficient amounts to meet recommended intake. N-3 PUFA-enriched eggs can be produced by modifying hens diets. When 70 g/kg of cod liver oil, canola oil, or linseed oil are added to a commercial control diet, the n-3 PUFA are increased from 1.2% of egg yolk fatty acids to 6.3, 4.6, and 7.8%, respectively. Feeding flaxseed increases linolenic acid in the egg yolk about 30-fold, and docosahexaenoic acid (DHA) increases nearly fourfold. When individuals are fed four n-3 PUFA-enriched eggs a day for 4 wk, plasma total cholesterol levels and low-density lipoprotein cholesterol (LDL-C) do not increase significantly. Plasma triglycerides (TG) are decreased by addition of n-3 PUFA-enriched eggs to the diet. N-3 PUFA may influence LDL particle size, causing a shift toward a less atherogenic particle. Blood platelet aggregation is significantly decreased in participants consuming n-3 PUFA-enriched eggs. Overall results of studies to date demonstrate positive effects and no negative effects from consumption of n-3-enriched eggs. Three n-3 PUFA-enriched eggs provide approximately the
Martins, Dulce Alves; Custódio, Luísa; Barreira, Luísa; Pereira, Hugo; Ben-Hamadou, Radhouan; Varela, João; Abu-Salah, Khalid M.
The main source of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in human nutrition is currently seafood, especially oily fish. Nonetheless, due to cultural or individual preferences, convenience, geographic location, or awareness of risks associated to fatty fish consumption, the intake of fatty fish is far from supplying the recommended dietary levels. The end result observed in most western countries is not only a low supply of n-3 LC-PUFA, but also an unbalance towards the intake of n-6 fatty acids, resulting mostly from the consumption of vegetable oils. Awareness of the benefits of LC-PUFA in human health has led to the use of fish oils as food supplements. However, there is a need to explore alternatives sources of LC-PUFA, especially those of microbial origin. Microalgae species with potential to accumulate lipids in high amounts and to present elevated levels of n-3 LC-PUFA are known in marine phytoplankton. This review focuses on sources of n-3 LC-PUFA, namely eicosapentaenoic and docosahexaenoic acids, in marine microalgae, as alternatives to fish oils. Based on current literature, examples of marketed products and potentially new species for commercial exploitation are presented. PMID:23807546
Kutzner, Laura; Ostermann, Annika I; Konrad, Thade; Riegel, Dieter; Hellhake, Stefan; Schuchardt, Jan Philipp; Schebb, Nils Helge
Supplementation products containing n-3 PUFA from marine sources serve a large market. Although the amount of eicosapentaenoic acid and docosahexaenoic acid in the products is provided by the manufacturer, no or little information is available on their lipid pattern. Therefore, we quantitatively analyzed the fatty acid pattern in the lipid fractions triglycerides, phospholipids, ethyl esters, and free fatty acids in supplementation products by means of solid phase extraction and gas chromatography. Twelve products from the European and U.S. markets containing fish, krill, algal, or plant oil were analyzed. Total n-3 PUFA content ranged from 68 g/100 g fat (fish oil) to 42 g/100 g fat (algal oil) to 17 g/100 g fat (krill oil). On the basis of the n-3 PUFA containing lipid class, the supplements can be separated dominantly in ethyl ester, re-esterified triglyceride, triglyceride, and phospholipid containing products. Algae-based products contained natural triglycerides, krill oils a complex mixture of phospholipids, triglycerides, and free fatty acids, and fish oil products either ethyl esters, re-esterified triglycerides, or triglycerides. Even products of the same class and source showed distinct differences in their lipid pattern. A specification of the lipid composition of n-3 PUFA products would allow distinguishing the different (qualities of) supplements.
Marangoni, Franca; Poli, Andrea
n-3 polyunsaturated fatty acids (n-3 PUFAs) are essential for mammalian cells that are not able to synthesise de novo their precursor, α-linolenic acid, and may only partially convert it to eicosapentaenoic acid (EPA) and to a very small extent to docosahexaenoic acid (DHA). For this reason, nutritional guidelines for cardiovascular prevention recommend regular fish consumption (approximately two portions per week) in order to increase the intake of the n-3 PUFAs EPA and DHA, mainly referring to fatty fish, living in cold waters, usually very rich in these fatty acids. However, the indication to consume fish regularly is unlikely to be sufficient to ensure that patients with documented coronary heart diseases receive the daily amount of EPA+DHA (ca. 1g) necessary for effective secondary prevention of the disease. This has prompted the development of pharmaceutical formulations both for dietary supplementation and for therapeutic administration, based on several dietary sources, containing greatly variable amounts of EPA and DHA, often with different availabilities. Critical knowledge of these characteristics allows the selection of the best approach in order to optimise the n-3 PUFA supply in various individuals.
Danforth, H D; Allen, P C; Levander, O A
A study of development of Eimeria tenella in chickens fed high n-3 fatty acids (n-3FA) diets showed ultrastructural degeneration of both asexual and sexual parasite stages. Abnormal shedding of asexual and sexual parasite developmental stages into the cecal lumen was also observed. Ultrastructural degeneration was characterized by cytoplasmic vacuolization, chromatin condensation within the nucleus, a lack of parasitophorous vacuole delineation, and, in some cases, a complete loss of parasite ultrastructural organization. The results of this study indicate that diets high in n-3FA may be useful in the control of avian coccidia.
Le Goff, Wilfried
Omega-3 fatty acids (n-3) FA are reported to be protective against cardiovascular disease (CVD), notably through their beneficial action on atherosclerosis development. In this context dietary intake of long-chain marine eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is recommended and randomised trials largely support that EPA and DHA intake is associated with a reduction of CVD. However, mechanisms governing the atheroprotective action of n-3 FA are still unclear and numerous studies using mouse models conducted so far do not allow to reach a precise view of the cellular and molecular effects of n-3 FA on atherosclerosis. In the current issue of Atherosclerosis, Chang et al. provide important new information on the anti-atherogenic properties of n-3 FA by analysing the incremental replacement of saturated FA by pure fish oil as a source of EPA and DHA in Ldlr(-/-) mice fed a high fat/high cholesterol diet.
Petracci, Massimiliano; Bianchi, Maurizio; Cavani, Claudio
Rabbit meat is a highly digestible, tasty, low-calorie food, often recommended by nutritionists over other meats. Currently research in the rabbit sector is interested in developing feeding strategies aiming to further increase the nutritional value of rabbit meat as a "functional food" by including n-3 polyunsaturated fatty acids (n-3 PUFA), conjugated linoleic acid (CLA), vitamins and antioxidants in rabbit diets and assessing their effects on both raw and stored/processed meat quality properties. Our recent studies indicate that the dietary inclusion from 3 to 6% of linseed might be considered as a way to achieve the enrichment of the meat with α-linolenic acid and to guarantee satisfactory product stability during further processing and storage. Considering that 6% dietary linseed corresponds to a n-3 PUFA content of 8.5% of the total fatty acids and a lipid content of 4.7 g/100 g of leg meat, a content of 396 mg n-3 PUFA/100g meat can be estimated, which represents about 19% of the recommended daily allowance (RDA) for n-3 PUFA.
Pusceddu, Matteo M.; Kelly, Philip; Stanton, Catherine; Cryan, John F.
Objective: The impact of lifetime dietary habits and their role in physical, mental, and social well-being has been the focus of considerable recent research. Omega-3 polyunsaturated fatty acids as a dietary constituent have been under the spotlight for decades. Omega-3 polyunsaturated fatty acids constitute key regulating factors of neurotransmission, neurogenesis, and neuroinflammation and are thereby fundamental for development, functioning, and aging of the CNS. Of note is the fact that these processes are altered in various psychiatric disorders, including attention deficit hyperactivity disorder, depression, and Alzheimer’s disease. Design: Relevant literature was identified through a search of MEDLINE via PubMed using the following words, “n-3 PUFAs,” “EPA,” and “DHA” in combination with “stress,” “cognition,” “ADHD,” “anxiety,” “depression,” “bipolar disorder,” “schizophrenia,” and “Alzheimer.” The principal focus was on the role of omega-3 polyunsaturated fatty acids throughout the lifespan and their implication for psychopathologies. Recommendations for future investigation on the potential clinical value of omega-3 polyunsaturated fatty acids were examined. Results: The inconsistent and inconclusive results from randomized clinical trials limits the usage of omega-3 polyunsaturated fatty acids in clinical practice. However, a body of literature demonstrates an inverse correlation between omega-3 polyunsaturated fatty acid levels and quality of life/ psychiatric diseases. Specifically, older healthy adults showing low habitual intake of omega-3 polyunsaturated fatty acids benefit most from consuming them, showing improved age-related cognitive decline. Conclusions: Although further studies are required, there is an exciting and growing body of research suggesting that omega-3 polyunsaturated fatty acids may have a potential clinical value in the prevention and treatment of psychopathologies. PMID:27608809
Johnson, Elizabeth J; Schaefer, Ernst J
Dementia and age-related macular degeneration (AMD) are major causes of disability in the elderly. n-3 Fatty acids, particularly docosahexaenoic acid (DHA), are highly concentrated in brain and retinal tissue and may prevent or delay the progression of dementia and AMD. Low dietary intakes and plasma concentrations have been reported to be associated with dementia, cognitive decline, and AMD risk. The major dietary sources of DHA are fish and fish oils, although dietary supplements are available. At this point, it is not possible to make firm recommendations regarding n-3 fatty acids and the prevention of dementia and AMD. Our own unpublished observations from the Framingham Heart Study suggest that > or =180 mg/d of dietary DHA (approximately 2.7 fish servings/wk) is associated with an approximately 50% reduction in dementia risk. At least this amount of DHA is generally found in one commercially available 1-g fish oil capsule given daily.
Uygur, R; Yagmurca, M; Alkoc, O A; Genc, A; Songur, A; Ucok, K; Ozen, O A
The aim of this study was to investigate the effects of quercetin and fish n-3 fatty acids on the changes in testis induced by ethanol. Forty-five rats divided into five groups, control, ethanol, ethanol+quercetin, ethanol+fish n-3 fatty acids and ethanol+quercetin+fish n-3 fatty acids. At the end of 8 weeks, all the rats were sacrificed. Degenerative changes in histopathological analyses, the decreased body weight gain and seminiferous tubule diameters in ethanol group have been observed. TUNEL assay also showed an increase in apoptotic cell number. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase (XO) and testosterone levels were decreased as well as the levels of malondialdehyde (MDA) and nitric oxide (NO) were increased in ethanol group. Histopathological changes caused by ethanol have been improved by quercetin and fish n-3 fatty acids. It was also found that protection was provided by increasing SOD, CAT and GSH-Px activities in groups administered quercetin, fish n-3 fatty acids and quercetin+fish n-3 fatty acids, and by decreasing the levels of MDA and NO in groups administered both quercetin and fish n-3 fatty acids together. These results suggest that quercetin and fish n-3 fatty acids are beneficial agents to reduce testicular injury induced by ethanol except for testosterone levels.
Camelina sativa is an oilseed plant rich in n-3 and n-6-fatty acids and extruding defatted seed meal results in high protein meal (~40%) containing residual n-3 fatty acids. We examined the effects of feeding extruded defatted camelina seed meal to commercial laying hens on egg production, quality, ...
Abdelmagid, Salma A.; MacKinnon, Jessica L.; Janssen, Sarah M.; Ma, David W.L.
Diet and exercise are recognized as important lifestyle factors that significantly influence breast cancer risk. In particular, dietary n-3 polyunsaturated fatty acids (PUFAs) have been shown to play an important role in breast cancer prevention. Growing evidence also demonstrates a role for exercise in cancer and chronic disease prevention. However, the potential synergistic effect of n-3 PUFA intake and exercise is yet to be determined. This review explores targets for breast cancer prevention that are common between n-3 PUFA intake and exercise and that may be important study outcomes for future research investigating the combined effect of n-3 PUFA intake and exercise. These lines of evidence highlight potential new avenues for research and strategies for breast cancer prevention. PMID:27812288
Prior, Pedro Luis; Galduróz, José Carlos Fernandes
New discoveries in the field of neurophysiology and neuropharmacology have revealed the role of (n-3) fatty acids in controlling inflammation and protecting neuron cells from oxidative damage, preserving their function. It has also been thought that their psychoactive properties could be beneficial in certain psychiatric illnesses. This article discusses the newest discoveries of the affected activities by these fats in the cerebral cortex and the efforts that have been made to put them in practice in clinical trials in humans. In general, we were able to detect certain discord in the scientific community when designing placebo-based studies (mainly in establishing the appropriate therapeutic dose of (n-3) fatty acids, varying from the recommended dietary dose to an amount that may be 3 or 4 times higher), and in interpreting results. Although many studies have had the validity of their results questioned because of their small sample size, several studies seem to indicate that the (n-3) fatty acids are useful therapeutic tools in treating psychiatric conditions such as major depression, bipolar disorder, and several other disorders. Larger sample size studies are still required to better analyze the treatment potential of these agents. PMID:22585900
Riediger, Natalie D; Azordegan, Nazila; Harris-Janz, Sydney; Ma, David W L; Suh, Miyoung; Moghadasian, Mohammed H
Cardiovascular benefits of dietary n-3 fatty acids have been shown. However, benefits of n-3 fatty acids as part of a high fat, low n-6:n-3 fatty acid ratio diet has not been fully characterized. Aim of this study is to investigate cardiovascular and metabolic benefits of 'designer oils' containing a low ratio of n-6:n-3 fatty acids in C57BL/6 mice. Three groups of C57BL/6 mice were fed an atherogenic diet supplemented with either a fish oil- or flaxseed oil-based 'designer oil' with an approximate n-6:n-3 fatty acid ratio of 2:1 (treated groups, n = 6 each) or with a safflower oil-based formulation with a high ratio (25:1) of n-6:n-3 fatty acids (control group, n = 6) for 6 weeks. Food intake, body weight, and blood lipid levels were monitored regularly. Fatty acid profile of the heart tissues was assessed. Histological assessment of liver samples was conducted. At the end of the study body weight and food intake was significantly higher in the flax group compared to control. The levels of 20:5n-3 and 22:6n-3 was significantly increased in the heart phospholipids in both flax and fish groups compared to control; tissue 20:4n-6 was significantly reduced in the fish group compared to control. Significant liver pathology was observed in the control group only. Lowering dietary ratio of n-6:n-3 fatty acids may significantly reduce cardiovascular and metabolic risks in mice regardless of the source of n-3 fatty acids.
Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed
The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat.
Wang, Wei; Shinto, Lynne; Connor, William E; Quinn, Joseph F
Carotenoids are fat-soluble antioxidants that may protect polyunsaturated fatty acids, such as n-3 fatty acids from oxidation, and are potentially important for Alzheimer's disease (AD) prevention and treatment. Fasting plasma carotenoids were measured in 36 AD subjects and 10 control subjects by HPLC. Correlations between plasma carotenoid levels, red blood cell (RBC) n-3 fatty acids, and dementia severity were examined in AD patients. Moderately severe AD patients (MMSE=16-19) had much lower plasma levels of two major carotenoids: lutein and beta-carotene, compared to mild AD patients (MMSE=24-27) or controls. Among AD patients, variables (lutein, beta-carotene, RBC docosahexaenoic acid (DHA) and LDL-cholesterol) were significantly correlated with MMSE. A lower MMSE score was associated with lower lutein, beta-carotene and RBC DHA levels, and a higher LDL-cholesterol level. These variables explained the majority of variation in dementia severity (55% of variance in MMSE). Lutein, beta-carotene and beta-cryptoxanthin were positively correlated with RBC DHA in AD patients. The association between higher carotenoids levels and DHA and higher MMSE scores, supports a protective role of both types of nutrients in AD. These findings suggest targeting multiple specific nutrients, lutein, beta-carotene, and DHA in strategies to slow the rate of cognitive decline.
van den Elsen, Lieke; Garssen, Johan; Willemsen, Linette
The diet is considered to have a major impact on human health. Dietary lipids including long chain polyunsaturated fatty acids (LCPUFA) possess potent immunomodulatory activities. Over the last decades the incidence of inflammatory disorders including allergic and cardiovascular diseases (CVD) has been rising. This phenomenon is associated with deficiencies in N-3 LCPUFA, found in fatty fish, and increased content of N-6 LCPUFA in the Western diet. LCPUFA act via different mechanisms including membrane fluidity, raft composition, lipid mediator formation, signaling pathways and transmembrane receptors. N-3 LCPUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce the development of allergic disease by affecting both the innate and adaptive immune system involved in the initiation and persistence of allergic disease. Fish oil has been shown to be effective in the primary prevention of allergic disease in infants at risk when supplemented during pregnancy and lactation. Subtle effects of N-3 LCPUFA on the outcome of the immune response may underlie these protective effects. This review describes the currently reported effects of LCPUFA on dendritic cells, T cells, B cells and mast cells. Also CVD are positively affected by N-3 LCPUFA. Populations consuming high amounts of oily fish are protected against CVD. Moreover N-3 LCPUFA are effective in the secondary prevention of cardiovascular events. Amongst other effects, EPA and DHA have been shown to suppress endothelial cell activation hereby reducing adhesion molecule expression and endothelial cell - leukocyte interactions. This review describes the mechanistic basis of the preventive role for N-3 LCPUFA in allergic disease and CVD.
Toufektsian, Marie-Claire; Salen, Patricia; Laporte, François; Tonelli, Chiara; de Lorgeril, Michel
Flavonoids probably contribute to the health benefits associated with the consumption of fruit and vegetables. However, the mechanisms by which they exert their effects are not fully elucidated. PUFA of the (n-3) series also have health benefits. Epidemiological and clinical studies have suggested that wine flavonoids may interact with the metabolism of (n-3) PUFA and increase their blood and cell levels. The present studies in rats were designed to assess whether flavonoids actually increase plasma levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main very long-chain (n-3) PUFA. Rats were fed a corn-derived anthocyanin (ACN)-rich (ACN-rich) or ACN-free diet with constant intakes of plant and marine (n-3) PUFA for 8 wk (Expt. 1). Plasma fatty acids were measured by GC. The ACN-rich diet contained ~0.24 ± 0.01 mg of ACN/g pellets. There were no significant differences between groups in the main saturated, monounsaturated, and (n-6) fatty acids. In contrast, plasma EPA and DHA were greater in the ACN-rich diet group than in the ACN-free diet group (P < 0.05). We obtained similar results in 2 subsequent experiments in which rats were administered palm oil (80 μL/d) and consumed the ACN-rich or ACN-free diet (Expt. 2) or were supplemented with fish oil (60 mg/d, providing 35 mg DHA and 12 mg EPA) and consumed the ACN-rich or ACN-free diet (Expt. 3). In both experiments, plasma EPA and DHA were significantly greater in the ACN-rich diet group. These studies demonstrate that the consumption of flavonoids increases plasma very long-chain (n-3) PUFA levels. These data confirm previous clinical and epidemiological studies and provide new insights into the health benefits of flavonoids.
Alexander-Aguilera, Alfonso; Berruezo, Silvia; Hernández-Diaz, Guillermo; Angulo, Ofelia; Oliart-Ros, Rosamaria
The fatty acid profile of hepatocytes and adipocytes is determined by the composition of the dietary lipids. It remains unclear which fatty acid components contribute to the development or reduction of insulin resistance. The present work examined the fatty acid composition of both tissues in sucrose-induced obese rats receiving fish oil to determine whether the effect of dietary (n-3) polyunsaturated fatty acids (PUFAs) on the reversion of metabolic syndrome in these rats is associated to changes in the fatty acid composition of hepatocyte and adipocyte membrane lipids. Animals with metabolic syndrome were divided into a corn-canola oil diet group and a fish oil diet group, and tissues fatty acids composition were analyzed after 6 weeks of dietary treatment. Fatty acid profiles of the total membrane lipids were modified by the fatty acid composition of the diets fed to rats. N-3 PUFAs levels in animals receiving the fish oil diet plus sucrose in drinking water were significantly higher than in animals under corn-canola oil diets. It is concluded that in sucrose-induced obese rats, consumption of dietary fish oil had beneficial effects on the metabolic syndrome and that such effects would be conditioned by the changes in the n-3 PUFAs composition in hepatic and adipose tissues because they alter membrane properties and modify the type of substrates available for the production of active lipid metabolites acting on insulin resistance and obesity.
Bourre, J M; Dumont, O; Durand, G
In a previous work, we calculated the dietary alpha-linolenic requirements (from vegetable oil triglycerides) for obtaining and maintaining a physiological level of (n-3) fatty acids in developing animal membranes as determined by the cervonic acid content [22:6(n-3), docosahexaenoic acid]. The aim of the present study was to measure the phospholipid requirement, as these compounds directly provide the very long polyunsaturated fatty acids found in membranes. Two weeks before mating, eight groups of female rats (previously fed peanut oil deficient in alpha-linolenic acid) were fed different semisynthetic diets containing 6% African peanut oil supplemented with different quantities of phospholipids obtained from bovine brain lipid extract, so as to add (n-3) polyunsaturated fatty acids to the diet. An additional group was fed peanut oil with rapeseed oil, and served as control. Pups were fed the same diet as their respective mothers, and were killed at weaning. Forebrain, sciatic nerve, retina, nerve endings, myelin, and liver were analyzed. We conclude that during the combined maternal and perinatal period, the (n-3) fatty acid requirement for adequate deposition of (n-3) polyunsaturated fatty acids in the nervous tissue (and in liver) of pups is lower if animals are fed (n-3) very long chain polyunsaturated fatty acids found in brain phospholipids [this study, approximately 60 mg of (n-3) fatty acids/100 g of diet, i.e., approximately 130 mg/1,000 kcal] rather than alpha-linolenic acid from vegetable oil triglycerides [200 mg of (n-3) fatty acids/100 g of diet, i.e., approximately 440 mg/1,000 kcal].
Nettleton, Joyce A; Katz, Robert
Historically, epidemiologic studies have reported a lower prevalence of impaired glucose tolerance and type 2 diabetes in populations consuming large amounts of the n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) found mainly in fish. Controlled clinical studies have shown that consumption of n-3 LC-PUFAs has cardioprotective effects in persons with type 2 diabetes without adverse effects on glucose control and insulin activity. Benefits include lower risk of primary cardiac arrest; reduced cardiovascular mortality, particularly sudden cardiac death; reduced triglyceride levels; increased high-density lipoprotein levels; improved endothelial function; reduced platelet aggregability; and lower blood pressure. These favorable effects outweigh the modest increase in low-density lipoprotein levels that may result from increased n-3 LC-PUFA intake. Preliminary evidence suggests increased consumption of n-3 LC-PUFAs with reduced intake of saturated fat may reduce the risk of conversion from impaired glucose tolerance to type 2 diabetes in overweight persons. Reported improvements in hemostasis, slower progression of artery narrowing, albuminuria, subclinical inflammation, oxidative stress, and obesity require additional confirmation. Expected health benefits and public health implications of consuming 1 to 2 g/day n-3 LC-PUFA as part of lifestyle modification in insulin resistance and type 2 diabetes are discussed.
Willemsen, Linette E M
The rise in non-communicable diseases, such as allergies, in westernized countries links to changes in lifestyle and diet. N-3 long chain polyunsaturated fatty acids (LCPUFA) present in marine oils facilitate a favorable milieu for immune maturation and may contribute to allergy prevention. N-3 LCPUFA can suppress innate and adaptive immune activation and induce epigenetic changes. Murine studies convincingly show protective effects of fish oil, a source of n-3 LCPUFA, in food allergy and asthma models. Observational studies in human indicate that high dietary intake of n-3 LCPUFA and low intake of n-6 PUFA may protect against the development of allergic disease early in life. High n-6 PUFA intake is also associated with an increased asthma risk while n-3 LCPUFA may be protective and reduce symptoms. The quality of the marine oil used has impact on efficacy of allergy prevention and several observations link in particular n-3 LCPUFA DHA to allergy suppression. Randomized controlled trials indicate that optimal timing, duration and dosage of n-3 LC-PUFA is required to exert an allergy protective effect. Supplementation during early pregnancy and lactation has shown promising results regarding allergy prevention. However these findings should be confirmed in a larger cohort. Although clinical trials in asthma patients reveal no consistent clinical benefits of n-3 LCPUFA supplementation on lung function, it can suppress airway inflammation. Future food-pharma approaches may reveal whether adjunct therapy with dietary n-3 LCPUFA can improve allergy prevention or immunotherapy via support of allergen specific oral tolerance induction or contribute to the efficacy of drug therapy for asthma patients.
Li, Yanli; Tang, Yuan; Wang, Shoujie; Zhou, Jing; Zhou, Jia; Lu, Xiao; Bai, Xiaochun; Wang, Xiang-Yang; Chen, Zhengliang; Zuo, Daming
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A) was administered intravenously to wild-type (WT) and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase activity, and inhibited production of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-17A, and IFN-γ). In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n-3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism and could be exploited as a new therapeutic approach for autoimmune hepatitis. PMID:27679638
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 ...
Background Although several studies have reported an association between mental disorders and serum levels of brain-derived neurotrophic factor (BDNF), this association is still poorly understood. The study of factors associated with both BDNF levels and mental disorders, such as n-3 polyunsaturated fatty acids (n-3 PUFAs), may help to elucidate the mechanisms mediating the relationship between the two variables. Therefore, the present study aimed to evaluate whether the intake n-3 PUFAs correlates with serum levels of BDNF. Findings This study involved 137 adolescents drawn from a community sample, including a group with high levels of anxiety, assessed using the Screen for Children and Anxiety Related Emotional Disorders. Blood samples were collected and serum BDNF levels were measured. n-3 PUFAs were estimated using a food frequency questionnaire for adolescents. Correlations were performed to assess the association between n-3 PUFAs intake and BDNF levels. Effects of potential confounders (total fat consumption, age, gender and anxiety) were examined using linear regression models. There was a direct correlation between n-3 PUFAs consumption and serum BDNF levels, which remained significant even after accounting for potential confounders. Conclusions We were able to detect a correlation between n-3 PUFAs intake and peripheral BDNF levels. Our study was limited by its small sample size, and our external validity may be restricted by the oversampling of anxious adolescents. Our findings may help determine the nature of the association between mental disorders and serum levels of BDNF. However, more studies are needed to elucidate the possible mechanisms by which n-3 PUFAs intake affects BDNF levels, and how this may lead to an increased vulnerability to psychiatric disorders. PMID:24593295
Calder, Philip C
Lipids traditionally used in artificial nutrition are based on n-6 fatty acid-rich vegetable oils like soyabean oil. This may not be optimal because it may present an excessive supply of linoleic acid. One alternative to the use of soyabean oil is its partial replacement by fish oil, which contains n-3 fatty acids. These fatty acids influence inflammatory and immune responses and so may be useful in particular situations where those responses are not optimal. Fish oil-containing lipid emulsions have been used in parenteral nutrition in adult patients post-surgery (mainly gastrointestinal). This has been associated with alterations in patterns of inflammatory mediators and in immune function and, in some studies, a reduction in length of intensive care unit (ICU) and hospital stay. Perioperative administration of fish oil may be superior to post-operative. Parenteral fish oil has been used in critically ill adults. Here the influence on inflammatory processes, immune function and clinical endpoints is not clear, since there are too few studies and those that are available report contradictory findings. Fish oil is included in combination with other nutrients in various enteral formulas. In post-surgical patients and in those with mild sepsis or trauma, there is clinical benefit from a formula including fish oil and arginine. A formula including fish oil, borage oil and antioxidants has demonstrated marked benefits on gas exchange, ventilation requirement, new organ failures, ICU stay and mortality in patients with acute respiratory distress syndrome, acute lung injury or severe sepsis.
Patterson, Joshua T; Green, Christopher C
Lipid dynamics of spawning fish are critical to the production of viable embryos and larvae. The present study utilized manipulation of dietary fatty acid (FA) profiles to examine the ability of spawning Gulf killifish (Fundulus grandis) to mobilize critical lipid components from somatic reserves or synthesize long-chain polyunsaturated FAs (LC-PUFAs) de novo from shorter-chain C18 precursors. An egg and multi-tissue evaluation of changes in FA concentrations across time after fish were switched from LC-PUFA-rich to LC-PUFA-deficient experimental diets was employed. The two experimental diets contained lipid sources which differed drastically in n-3 C18 FA content but had similar levels of n-6 C18 FAs. Discrete effects of dietary n-3 FAs can be analyzed because n-3 and n-6 represent distinct metabolic families which cannot be exchanged in vivo. Results indicate that a combination of mobilization and de novo synthesis is likely utilized to maintain physiologically required FA levels in critical tissues and embryos. Mobilization was supported by decreases in LC-PUFAs in somatic tissues and decreases in intraperitoneal fat content and liver mass. Evidence for biosynthesis was provided by a higher level of n-3 LC-PUFAs in the liver and ova of fish fed diets containing n-3 C18 precursors versus those fed diets with low levels of precursor FAs. The characteristic physiological plasticity of Gulf killifish is exemplified in the nutritional domain by its management of dietary FA deficiency.
Bhaswant, Maharshi; Poudyal, Hemant; Brown, Lindsay
The widespread acceptance that increased dietary n-3 polyunsaturated fatty acids (PUFAs), especially α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), improve health is based on extensive studies in animals, isolated cells and humans. Visceral adiposity is part of the metabolic syndrome, together with insulin resistance, dyslipidemia, hypertension and inflammation. Alleviation of metabolic syndrome requires normalization of insulin release and responses. This review assesses our current knowledge of the mechanisms that allow n-3 PUFAs to improve insulin secretion and sensitivity. EPA has been more extensively studied than either ALA or DHA. The complex actions of EPA include increased G-protein-receptor-mediated release of glucagon-like peptide 1 (GLP-1) from enteroendocrine L-cells in the intestine, up-regulation of the apelin pathway and down-regulation of other control pathways to promote insulin secretion by the pancreatic β-cells, together with suppression of inflammatory responses to adipokines, inhibition of peroxisome proliferator-activated receptor α actions and prevention of decreased insulin-like growth factor-1 secretion to improve peripheral insulin responses. The receptors involved and the mechanisms of action probably differ for ALA and DHA, with antiobesity effects predominating for ALA and anti-inflammatory effects for DHA. Modifying both GLP-1 release and the actions of adipokines by n-3 PUFAs could lead to additive improvements in both insulin secretion and sensitivity.
Rousseau, D.; Helies-Toussaint, C.; Raederstorff, D.; Moreau, D.; Grynberg, A.
The consequences of a dietary n-3 PUFA supply was investigated on the blood pressure (BP) increase elicited by left renal artery stenosis in rats distributed in 3 groups (n = 8) fed for 8 weeks a semi-purified diet either as control diet or enriched diets (docosahexaenoic acid, DHA, or eicosapentaenoic acid, EPA). The PUFA intake induced large alterations in heart and kidney phospholipid fatty acid profile, but did not influence body weight, cardiac hypertrophy, renal left atrophy and right hypertrophy. Within 4 weeks, BP raised from 120-180 +/- 2 mm Hg in the control group, but only to 165 +/- 3 mm Hg in the n-3 PUFA groups. After stabilization of BP in the 3 groups, the rats received a short administration of increasing dose of perindopril. The lower dose (0.5 mg/kg) moderately decreased BP only in the control group. With higher doses (1, 5 and 10 mg/kg) BP was normalized in the 3 groups, with a higher amplitude of the BP lowering effect in the control group. A moderate n-3 PUFA intake can contribute to prevent the development of peripheral hypertension in rats by a mechanism that may involve angiotensin converting enzyme.
Todorčević, Marijana; Hodson, Leanne
Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the n-3 fatty acids, specifically eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity. PMID:26729182
Dal Bello, B; Torri, L; Piochi, M; Zeppa, G
The concentration of n-3 polyunsaturated fatty acids (PUFA) in yogurt was increased using 5 different vegetable oils obtained from flaxseed, Camelina sativa, raspberry, blackcurrant, and Echium plantagineum. The vegetable oils were added to partially skim milk before lactic fermentation at a concentration adequate enough to cover at least 10% of the recommended daily intake of 2 g/d of α-linolenic acid according to EC regulation no. 432/2012. Microbiological (lactobacilli and streptococci, yeast, and molds), chemical (pH, syneresis, proximate composition, fatty acids, oxidation stability), and sensory evaluations were assessed for all of the fortified yogurts after 0, 7, 14, and 21 d of storage at 4°C. Sensory evaluations were conducted at 21 d of storage at 4°C. Among the yogurts produced, those that were supplemented with flaxseed and blackcurrant oils exhibited the highest α-linolenic acid content (more than 200mg/100 g of yogurt) at the end of storage. The addition of oil did not influence the growth of lactic acid bacteria that were higher than 10(7) cfu/g at 21 d of storage. All of the yogurts were accepted by consumers, except for those supplemented with raspberry and E. plantagineum oils due to the presence of off flavors.
Mozaffarian, Dariush; Wu, Jason H Y
Considerable research supports cardiovascular benefits of consuming omega-3 PUFA, also known as (n-3) PUFA, from fish or fish oil. Whether individual long-chain (n-3) PUFA have shared or complementary effects is not well established. We reviewed evidence for dietary and endogenous sources and cardiovascular effects on biologic pathways, physiologic risk factors, and clinical endpoints of EPA [20:5(n-3)], docosapentaenoic acid [DPA, 22:5(n-3)], and DHA [22:6(n-3)]. DHA requires direct dietary consumption, with little synthesis from or retroconversion to DPA or EPA. Whereas EPA is also largely derived from direct consumption, EPA can also be synthesized in small amounts from plant (n-3) precursors, especially stearidonic acid. In contrast, DPA appears principally derived from endogenous elongation from EPA, and DPA can also undergo retroconversion back to EPA. In experimental and animal models, both EPA and DHA modulate several relevant biologic pathways, with evidence for some differential benefits. In humans, both fatty acids lower TG levels and, based on more limited studies, favorably affect cardiac diastolic filling, arterial compliance, and some metrics of inflammation and oxidative stress. All three (n-3) PUFA reduce ex vivo platelet aggregation and DHA also modestly increases LDL and HDL particle size; the clinical relevance of such findings is uncertain. Combined EPA+DHA or DPA+DHA levels are associated with lower risk of fatal cardiac events and DHA with lower risk of atrial fibrillation, suggesting direct or indirect benefits of DHA for cardiac arrhythmias (although not excluding similar benefits of EPA or DPA). Conversely, EPA and DPA, but not DHA, are associated with lower risk of nonfatal cardiovascular endpoints in some studies, and purified EPA reduced risk of nonfatal coronary syndromes in one large clinical trial. Overall, for many cardiovascular pathways and outcomes, identified studies of individual (n-3) PUFA were relatively limited, especially
Kakani, Radhika; Fowler, Justin; Haq, Akram-Ul; Murphy, Eric J; Rosenberger, Thad A; Berhow, Mark; Bailey, Christopher A
Camelina sativa is an oilseed plant rich in n-3 and n-6 fatty acids and extruding the seeds results in high protein meal (*40%) containing high levels of n-3 fatty acids. In this study, we examined the effects of feeding extruded defatted camelina meal to commercial laying hens, measuring egg production, quality, and fatty acid composition. Lohmann White Leghorn hens (29 weeks old) were randomly allocated to three dietary treatment groups (n = 25 per group) and data was collected over a 12 week production period. All the treatment groups were fed a corn soy based experimental diet containing 0% (control), 5, or 10% extruded camelina meal. We found no significant differences in percent hen-day egg production and feed consumed per dozen eggs. Egg shell strength was significantly higher in both camelina groups compared to the controls. Egg total n-3 fatty acid content increased 1.9- and 2.7-fold in 5 and 10% camelina groups respectively relative to the control. A similar increase in DHA content also occurred. Further camelina meal did not alter glucosinolate levels and no detectable glucosinolates or metabolic product isothiocyanates were found in the eggs from either the 5 or 10% camelina groups. These results indicate that camelina meal is a viable dietary source of n-3 fatty acids for poultry and its dietary inclusion results in eggs enriched with n-3 fatty acids.
Smith, S. M.; Pierson, D. L.; Mehta, S. K.; Zwart, S. R.
Space flight has many negative effects on human physiology, including bone and muscle loss. Bone and muscle are two systems that are positively affected by dietary intake of fish and n-3 fatty acids. The mechanism is likely to be related to inhibition by n-3 fatty acids of inflammatory cytokines (such as TNF) and thus inhibition of downstream NF-kB activation. We have documented this effect in a 3-dimensional cell culture model, where NF-kB activation in osteoclasts was inhibited by eicosapentaenoic acid, an n-3 fatty acid. We have also indentified that NF-kB activation in peripheral blood mononuclear cells of Space Shuttle crews. We found that after Shuttle flights of 2 wk, expression of the protein p65 (evidence of NF-kB activation) was increased at landing (P less than 0.001). When evaluating the effects of n-3 fatty acid intake on bone breakdown after 60 d of bed rest (a weightlessness analog). We found that after 60 d of bed rest, greater intake of n-3 fatty acids was associated with less N-telopeptide excretion (Pearson r = -0.62, P less than 0.05). We also evaluated the relationship of fish intake and bone loss in astronauts after 4 to 6 mo missions on the International Space Station. Higher consumption of fish during flight was associated with higher bone mineral density (Pearson r = 0.46, P less than 0.05). Together, these findings provide evidence of the cellular mechanism by which n-3 fatty acids can inhibit bone loss, and preliminary human evidence of the potential for n-3 fatty acids to counteract bone loss associated with space flight. This study was supported by the NASA Human Research Program.
Katahdin (KK, n=6), Katahdin x Suffolk (KS, n=6), Suffolk x Katahdin (SK, n=6) and Suffolk (SS, n=6) wethers were used to evaluate omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acid content, and the ratio of n-6 to n-3 in muscles of these lambs, raised on concentrate or forage diets. Lambs ...
Yaniv, Z; Schafferman, D; Shamir, I; Madar, Z
Seeds of Matthiola incana contain oil rich (55-65%) in (n-3) linolenic acid. Selected lines were developed and evaluated for their agronomic and chemical parameters. Extracted oil was fed for 6 weeks to rats, which were compared with rats fed a diet containing coconut oil or sunflower oil. Cholesterol levels were significantly lowest in rats fed diets rich in M. incana oil (27% reduction), and triglycerides were significantly lower in rats receiving either M. incana or sunflower oil (36% reduction). The contents of arachidonic acid and other (n-6) fatty acids were significantly the lowest in the liver and plasma of rats that had received M. incana oil. The levels of (n-3) fatty acids were significantly greater in both the liver and plasma of rats fed M. incana oil. The ratio of (n-3)/(n-6) long-chain fatty acids in the plasma was 7 times higher in rats fed with M. incana oil than in those fed with sunflower oil and 6 times higher than in those fed coconut oil. The results demonstrate for the first time a beneficial effect of dietary M. incana oil in reducing cholesterol levels and increasing (n-3) fatty acid levels in the plasma. This new, terrestrial plant source of (n-3) fatty acids could replace marine oils and thereby contribute beneficially to the human diet.
Huang, Chao-Wei; Chien, Yi-Shan; Chen, Yu-Jen; Ajuwon, Kolapo M.; Mersmann, Harry M.; Ding, Shih-Torng
The incidence of obesity and its comorbidities, such as insulin resistance and type II diabetes, are increasing dramatically, perhaps caused by the change in the fatty acid composition of common human diets. Adipose tissue plays a role as the major energy reservoir in the body. An excess of adipose mass accumulation caused by chronic positive energy balance results in obesity. The n-3 polyunsaturated fatty acids (n-3 PUFA), DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) exert numerous beneficial effects to maintain physiological homeostasis. In the current review, the physiology of n-3 PUFA effects in the body is delineated from studies conducted in both human and animal experiments. Although mechanistic studies in human are limited, numerous studies conducted in animals and models in vitro provide potential molecular mechanisms of the effects of these fatty acids. Three aspects of n-3 PUFA in adipocyte regulation are discussed: (1) lipid metabolism, including adipocyte differentiation, lipolysis and lipogenesis; (2) energy expenditure, such as mitochondrial and peroxisomal fatty acid β-oxidation; and (3) inflammation, including adipokines and specialized pro-resolving lipid mediators. Additionally, the mechanisms by which n-3 PUFA regulate gene expression are highlighted. The beneficial effects of n-3 PUFA may help to reduce the incidence of obesity and its comorbidities. PMID:27735847
Calder, Philip C
Atherosclerosis has an important inflammatory component and acute cardiovascular events can be initiated by inflammatory processes occurring in advanced plaques. Fatty acids influence inflammation through a variety of mechanisms; many of these are mediated by, or associated with, the fatty acid composition of cell membranes. Human inflammatory cells are typically rich in the n-6 fatty acid arachidonic acid, but the contents of arachidonic acid and of the marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be altered through oral administration of EPA and DHA. Eicosanoids produced from arachidonic acid have roles in inflammation. EPA also gives rise to eicosanoids and these are usually biologically weak. EPA and DHA give rise to resolvins which are anti-inflammatory and inflammation resolving. EPA and DHA also affect production of peptide mediators of inflammation (adhesion molecules, cytokines, etc.). Thus, the fatty acid composition of human inflammatory cells influences their function; the contents of arachidonic acid, EPA and DHA appear to be especially important. The anti-inflammatory effects of marine n-3 polyunsaturated fatty acids (PUFAs) may contribute to their protective actions towards atherosclerosis and plaque rupture.
The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have important nutrition and disease management properties. Presently fish oil (FO) supplementation relies on capsular triglyceride. Flavored emulsified lipid preparations may provide an improved approach to FO del...
Proudman, Susanna M; Cleland, Leslie G; Metcalf, Robert G; Sullivan, Thomas R; Spargo, Llewellyn D; James, Michael J
A randomised controlled trial (RCT) of high-dose v. low-dose fish oil in recent-onset rheumatoid arthritis (RA) demonstrated that the group allocated to high-dose fish oil had increased remission and decreased failure of disease-modifying anti-rheumatic drug (DMARD) therapy. This study examines the relationships between plasma phospholipid levels of the n-3 fatty acids in fish oil, EPA and DHA, and remission and DMARD use in recent-onset RA. EPA and DHA were measured in blood samples from both groups of the RCT. The data were analysed as a single cohort, and Cox proportional hazards models were used to examine relationships between plasma phospholipid (PL) EPA and DHA and various outcome measures. When analysed as a single cohort, plasma PL EPA was related to time to remission, with a one unit increase in EPA (1% total fatty acids) associated with a 12% increase in the probability of remission at any time during the study period (hazard ratio (HR)=1.12; 95% CI 1.02, 1.23; P=0.02). Adjustment for smoking, anti-cyclic citrullinated peptide antibodies and 'shared epitope' HLA-DR allele status did not change the HR. Plasma PL EPA, adjusted for the same variables, was negatively related to time to DMARD failure (HR=0.85; 95% CI 0.72, 0.99; P=0.047). The HR for DHA and time to remission or DMARD failure were similar in magnitude to those for EPA, but not statistically significant. Biomarkers of n-3 status, such as plasma PL EPA, have the potential to predict clinical outcomes relevant to standard drug treatment of RA patients.
Yu, Haibo; Gao, Qinfeng; Dong, Shuanglin; Zhou, Jishu; Ye, Zhi; Lan, Ying
The present study was conducted to understand the effects of dietary n-3 highly unsaturated fatty acids (HUFAs) on growth, fatty acid profiles, antioxidant capacity and the immunity of sea cucumber Apostichopus japonicus (Selenka). Five experimental diets were prepared, containing graded levels of n-3 HUFAs (0.46%, 0.85%, 1.25%, 1.61% and 1.95%, respectively), and the 0.46% group was used as control group. The specific growth rates, fatty acid profiles, activities and gene expression of antioxidative enzymes and lysozyme of the sea cucumbers that were fed with the 5 experimental diets were determined. The results showed that the specific growth rate of sea cucumbers in all the treatment groups significantly increased compared to the control group (P < 0.05), indicating the positive effects of n-3 HUFAs on the growth of sea cucumbers. The contents of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in the body wall of the sea cucumbers gradually increased with the increasing levels of n-3 HUFAs in the diets. The suitable supplement of n-3 HUFAs in diets improved the activities of superoxide dismutase (SOD) and catalase (CAT) of sea cucumbers by up-regulating the expression of SOD and CAT mRNA in sea cucumbers. However, excess n-3 HUFAs in diets caused lipid peroxidation, inhibited the expression of lysozyme (LSZ) mRNA and decreased the activities of LSZ in sea cucumbers. In summary, the suitable supplement levels of n-3 HUFAs in diets of sea cucumbers A. japonicus were estimated between 0.85% and 1.25% considering the growth performance, cost and the indicators of antioxidant capacity and immunity.
Lemaitre, Rozenn N; Bartz, Traci M; King, Irena B; Brody, Jennifer A; McKnight, Barbara; Sotoodehnia, Nona; Rea, Thomas D; Johnson, Catherine O; Mozaffarian, Dariush; Hesselson, Stephanie; Kwok, Pui-Yan; Siscovick, David S
Whether genetic factors influence the associations of fatty acids with the risk of sudden cardiac arrest (SCA) is largely unknown. To investigate possible gene-fatty acid interactions on SCA risk, we used a case-only approach and measured fatty acids in erythrocyte samples from 1869 SCA cases in a population-based repository with genetic data. We selected 191 SNP in ENCODE-identified regulatory regions of fifty-five candidate genes in fatty acid metabolic pathways. Using linear regression and additive genetic models, we investigated the association of the selected SNP with erythrocyte levels of fatty acids, including DHA, EPA and trans-fatty acids among the SCA cases. The assumption of no association in non-cases was supported by analysis of publicly available datasets containing over 8000 samples. None of the SNP-fatty acid associations tested among the cases reached statistical significance after correction for multiple comparisons. One SNP, rs4654990 near PLA2G2A, with an allele frequency of 0·33, was nominally associated with lower levels of DHA and EPA and higher levels of trans-fatty acids. The strongest association was with DHA levels (exponentiated coefficient for one unit (1 % of total fatty acids), 0·90, 95 % CI 0·85, 0·97; P = 0·003), indicating that for subjects with a coded allele, the OR of SCA associated with one unit higher DHA is about 90 % what it is for subjects with one fewer coded allele. These findings suggest that the associations of circulating n-3 and trans-fatty acids with SCA risk may be more pronounced in carriers of the rs4654990 G allele.
Jans, Linda A W; Giltay, Erik J; Van der Does, A J Willem
Depressive symptoms are common during pregnancy and the post-partum period. Although essential n-3 PUFA may have beneficial effects on depression, it remains unclear whether they are also effective for perinatal depression. The purpose of the present study was to assess the efficacy of n-3 supplementation for perinatal depression, by performing a meta-analysis on currently available data. After a thorough literature search, we included seven randomised controlled trials in the meta-analysis, all with EPA and/or DHA supplementation. Most studies were judged to be of low-to-moderate quality, mainly due to small sample sizes and failure to adhere to Consolidated Standards of Reporting Trials guidelines. Some studies were not primarily designed to address perinatal depression. A total of 309 women on n-3 fatty acid supplementation were compared with 303 women on placebo treatment. n-3 Supplementation was not found to be significantly more effective than placebo at post-treatment with a pooled effect size (Hedges's g) of - 0.03 (95 % CI - 0.18, 0.13; P = 0.76) using a fixed-effects model. Heterogeneity was low-to-moderate (I2 = 30 %). In a subgroup analysis of three small studies of pregnant women with major depression, there was some indication of effectiveness (effect size 0.17; 95 % CI - 0.21, 0.55). In conclusion, the question of whether EPA and DHA administration is effective in the prevention or treatment of perinatal depression cannot be answered yet. Future research should focus on women who are clinically depressed (or at risk). The quality of research in this area needs to improve.
Kono, Hiroshi; Fujii, Hideki; Ogiku, Masahito; Tsuchiya, Masato; Ishii, Kenichi; Hara, Michio
The specific purpose of this study was to evaluate the significant effects of medium-chain triglycerides (MCTs) and N-3 fatty acids on chemically induced experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid (TNBS) in rats. Male Wistar rats were fed liquid diets enriched with N-6 fatty acid (control diets), N-3 fatty acid (MCT- diets), and N-3 fatty acid and MCT (MCT+ diets) for 2 weeks and then were given an intracolonic injection of TNBS. Serum and tissue samples were collected 5 days after ethanol or TNBS enema. The severity of colitis was evaluated pathologically, and tissue myeloperoxidase activity was measured in colonic tissues. Furthermore, protein levels for inflammatory cytokines and a chemokine were assessed by an enzyme-linked immunosorbent assay in colonic tissues. Induction of proinflammatory cytokines tumor necrosis factor-α and interleukin-1β in the colon by TNBS enema was markedly attenuated by the MCT+ diet among the 3 diets studied. Furthermore, the induction of chemokines macrophage inflammatory protein-2 and monocyte chemotactic protein-1 also was blunted significantly in animals fed the MCT+ diets. As a result, MPO activities in the colonic tissue also were blunted significantly in animals fed the MCT+ diets compared with those fed the control diets or the MCT- diets. Furthermore, the MCT+ diet improved chemically induced colitis significantly among the 3 diets studied. Diets enriched with both MCTs and N-3 fatty acids may be effective for the therapy of inflammatory bowel disease as antiinflammatory immunomodulating nutrients.
Cohen, Joshua T; Bellinger, David C; Connor, William E; Shaywitz, Bennett A
Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish also contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of prenatal n-3 intake on cognitive development. Other papers quantify the negative impact of prenatal exposure to MeHg on cognitive development, and the extent to which fish consumption protects against coronary heart disease mortality and stroke in adults. This paper aggregates eight randomized controlled trials (RCTs) comparing cognitive development in controls and in children who had received n-3 PUFA supplementation (seven studies of formula supplementation and one study of maternal dietary supplementation). Our analysis assigns study weights accounting for statistical precision, relevance of three endpoint domains (general intelligence, verbal ability, and motor skills) to prediction of IQ, and age at evaluation. The study estimates that increasing maternal docosahexaenoic acid (DHA) intake by 100 mg/day increases child IQ by 0.13 points. The paper notes that findings were inconsistent across the RCTs evaluated (although our findings were relatively robust to changes in the weighting scheme used). Also, for seven of the eight studies reviewed, effects are extrapolated from formula supplementation to maternal dietary intake.
Muley, Arti; Muley, Prasad; Shah, Monali
Diabetes mellitus (T2DM) has become a global problem. Role of n-3 FA in its prevention is still not completely understood. We carried out this systematic review and meta-analysis to assess the relation of dietary intake of fish and n-3PUFA with risk of diabetes. We searched PUBMED, EMBASE and GOOGLE with cross references to identify relevant articles. Since no RCTs were available, we searched for prospective cohort studies. Sixteen studies with 6,79,763 participants which assessed the association of dietary intake of fish and n-3 PUFA (marine or alpha-linolenic acid) with incidence of T2DM in > 18 years population and provided relative risk (RR) or hazard ratio (HR) with the corresponding 95% confidence interval (CI) of T2DM for each category of fish or n-3 PUFA intake were included. Three independent reviewers reviewed all eligible studies and abstracted the relevant information from individual studies. Meta-analysis confirmed the previous finding that marine n-3 FA increased risk of T2DM in Americans but reduced the same in Asians. We observed that two and seven times increased intake of ALA and fatty fish respectively reduced the risk of T2DM significantly and ALA did not increase the risk in Americans. We concluded that ALA may have some role in preventing T2DM, but is not studied widely. Hence, it should be studied in greater details (with higher degrees of intake; more than two times) to aid in developing effective preventive strategies against diabetes.
A survey is given on some newer knowledge about metabolism and about the importance of the essential fatty acids and of the n-3 fatty acids (eicosapentaenic, docosapentaenic, docosahexaenic acids) which occur in fish oils. In the body the linoleic acid via intermediate steps can be transformed into the arachidonic acid, from which various prostaglandins and leucotriens as well as the thromboxane A2 can be formed. The transformation of the linolenic acid into the eicosapentaenic acid is slight in man. The docosahexaenic acid is necessary for the construction of phospholipids in the brain and in the retina. The uptake of fish fatty acids inhibits the formation of thromboxane A2 and of leukotriens from the arachidonic acid. The fish fatty acids further in the liver in the peroxisomas the activity of the enzymes for the beta-oxidation; the formation of lipoproteins of high density increases under their influence: the triacylglyceride content, the cholesterol as well as the lipoprotein content of very low and low density decreases, when there is an adequate part of fish fatty acids in the nutrition.
Low fat diets are associated with risk reduction for chronic metabolic diseases compared to high fat diets. To evaluate effects of varied fat and fatty acid intake on lipid metabolism, phospholipid fatty acids (PLFA) were measured and delta 5 and 6 desaturase activities (D5D, D6D) were calculated in...
Bou, Marta; Østbye, Tone-Kari; Berge, Gerd M; Ruyter, Bente
The aim of the present study was to investigate how EPA, DHA, and lipoic acid (LA) influence the different metabolic steps in the n-3 fatty acid (FA) biosynthetic pathway in hepatocytes from Atlantic salmon fed four dietary levels (0, 0.5, 1.0 and 2.0%) of EPA, DHA or a 1:1 mixture of these FA. The hepatocytes were incubated with [1-(14)C] 18:3n-3 in the presence or absence of LA (0.2 mM). Increased endogenous levels of EPA and/or DHA and LA exposure both led to similar responses in cells with reduced desaturation and elongation of [1-(14)C] 18:3n-3 to 18:4n-3, 20:4n-3, and EPA, in agreement with reduced expression of the Δ6 desaturase gene involved in the first step of conversion. DHA production, on the other hand, was maintained even in groups with high endogenous levels of DHA, possibly due to a more complex regulation of this last step in the n-3 metabolic pathway. Inhibition of the Δ6 desaturase pathway led to increased direct elongation to 20:3n-3 by both DHA and LA. Possibly the route by 20:3n-3 and then Δ8 desaturation to 20:4n-3, bypassing the first Δ6 desaturase step, can partly explain the maintained or even increased levels of DHA production. LA increased DHA production in the phospholipid fraction of hepatocytes isolated from fish fed 0 and 0.5% EPA and/or DHA, indicating that LA has the potential to further increase the production of this health-beneficial FA in fish fed diets with low levels of EPA and/or DHA.
Popovic, Tamara; Ranic, Marija; Bulajic, Predrag; Milicevic, Miroslav; Arsic, Aleksandra; Vucic, Vesna; Glibetic, Marija
Nutritional and immunological status of patients with obstructive jaundice is usually severely altered, with high mortality rates. The n-3 polyunsaturate fatty acids (PUFA), particularly eicosapentaenoic acid (EPA, 20:5 n-3), posess potent immunomodulatory activities. Thus, our aim was to compare the plasma phospholipid fatty acid (FA) composition of these patients with healthy subjects, as well as before and after 7 days preoperative supplementation with high doses of EPA (0.9 g per day) and docosahexaenoic acid (DHA, 22:6 n-3, 0.6 g per day). We found impaired FA status in obstructive jaundice patients, especially EPA, DHA and PUFA, but significantly increased content of total n-3 FA, 22:5 n-3 FA and particularly EPA, which increased more than 3 fold, after 7 days supplementation. In addition, the n6/n3 ratio significantly decreased from 14.24 to 10.24, demonstrating severely improved plasma phospholipid profile in these patients after the intervention. PMID:19902030
Tinoco, Sandra M Barboza; Sichieri, Rosely; Setta, Cecília L; Moura, Anibal S; Carmo, Maria G Tavares do
Background Linoleic 18:2 (n-6) and α-linolenic 18:3 (n-3) essential fatty acids and long-chain polyunsaturated fatty acids (LC-PUFA) are essential nutrients for growth and neonatal development. Consumption of preformed n-3 LC-PUFA has been shown to increase gestational duration and to decrease the incidence of premature birth in human studies. This study evaluated the association of essential fatty acids and LC-PUFA in breast milk on the growth of premature children (weight, height and head circumference). Study design Thirty-seven premature infants with a gestational age of 37 weeks or less were followed until 6 months of gestational age, adjusted for prematurity. The milk from mothers, weight, height and head circumference measures of children were collected during the follow up. The breast milk fatty acids were quantified by gas-liquid chromatography. Results Our results showed that total n-3 PUFA was positively associated with weight gain (p = 0.05), height (p = 0.04) and body mass index (BMI) of children (p = 0.05). Our results also indicate that both linoleic acid and total essential fatty acids were positively associated with BMI and head circumference, whereas oleic acid was positively associated only with head circumference. Conclusion These results suggest that the n-3 PUFA composition of milk may be associated with weight gain and growth. Considering the advantages of n-3 LC-PUFA consumption on infant growth and visual function and its association with reduced incidence of premature birth, dietitians should advise pregnant women to increase their intake of foods high in n-3 LC-PUFA. PMID:19558659
Time trend investigation of PCBs, PBDEs, and organochlorine pesticides in selected n-3 polyunsaturated fatty acid rich dietary fish oil and vegetable oil supplements; nutritional relevance for human essential n-3 fatty acid requirements.
Jacobs, Miriam N; Covaci, Adrian; Gheorghe, Adriana; Schepens, Paul
In addition to being used in the food and animal feed industry, fish oils have also been used traditionally as dietary supplements. Due to the presence of long-chain n-3 fatty acids, fish oils have therapeutic benefits in the prevention and treatment of cardiovascular, immunological, and arthritic diseases, as well as childhood deficiency diseases such as rickets, because of a high content of vitamin D. However, fish oils are also susceptible to contamination with lipophilic organic chemicals that are now ubiquitous contaminants of marine ecosystems. Many vegetable oils are sources of the shorter chain precursor forms of n-3 fatty acids, and in recent years the specialist dietary supplement market has expanded to include these oils in a variety of different formulations. This paper reports analytical results of selected contaminants, including polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers, for a range of commercially available n-3 fatty acid rich fish and vegetable oil dietary supplements. Using principal component analysis, the values are compared with historic samples to elucidate time trends in contamination profiles. Levels of contaminants are discussed in relation to the nutritional benefits to the consumer of long- and short-chain forms of n-3 fatty acids.
Mandal, G. P.; Ghosh, T. K.; Patra, A. K.
The objective of this study was to investigate the different dietary ratios of n-6 to n-3 (n-6/n-3) fatty acid (FA) on performance and n-6/n-3 FA in muscles of broiler chickens. A total of 300 one-day-old Cobb chicks were randomly assigned to 3 treatments of 10 replicates in each (10 birds/replicate). Birds were fed on a corn-soybean meal-based diet containing 1% oil during starter (day 1 to 21) and 2% oil during finisher (day 22 to 39) phases, respectively. Treatments of high, medium and low dietary n-6/n-3 FA were formulated by replacing rice bran oil with linseed oil to achieve n-6/n-3 FA close to >20:1, 10:1 and 5:1, respectively. Average daily gain, average daily feed intake, and feed conversion ratio were similar (p>0.05) among the treatments. Serum glucose, cholesterol and triglycerides concentrations were not affected (p>0.05) by dietary treatments. In breast, concentration of C18:3n-3 was significantly greater (p = 0.001) for medium and low vs high n-6/n-3 FA, while concentrations of C20:5n-3, C22:6n-3, total n-3 FA, and n-6/n-3 FA were significantly higher for low vs medium, and medium vs high dietary n-6/n-3 FA. In contrast, concentrations of C18:2 and mono-unsaturated FA (MUFA) were lower for low vs high dietary n-6/n-3 FA. In thigh muscles, concentrations of C20:5n-3 were higher (p<0.05) for medium and low vs high dietary n-6/n-3 FA, and concentrations of C18:3n-3, C22:6, and n-3 FA were greater (p<0.05) for medium vs high, low vs medium dietary n-6/n-3 FA. However, concentrations of C18:1, MUFA, n-6/n-3 were lower (p<0.05) for low and medium vs high dietary n-6/n-3 FA. In conclusion, lowering the dietary n-6/n-3 FA did not affect the performance of chickens, but enhanced beneficial long-chain n-3 FA and decreased n-6/n-3 FA in chicken breast and thigh, which could be advantageous for obtaining healthy chicken products. PMID:25358321
Park, Yongsoon; Nam, Somyoung; Yi, Hyeong-Joong; Hong, Hyun-Jong; Lee, Myoungsook
Intake of n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been suggested to associate with an increased risk of hemorrhagic stroke. The present study was designed to investigate the hypothesis that EPA and DHA increase oxidative stress and hemorrhage volume in rats with intracerebral hemorrhagic (ICH) stroke. Thirty-five-week-old male rats were fed an American Institute of Nutrition-93M diet containing 0% (n = 27), 0.5% (n = 15), or 1% EPA + DHA of total energy for 5 weeks. Of 5 rats fed 1% EPA + DHA (41%), 5 died because of excessive bleeding within 12 hours after ICH surgery. Behavior test score and hemorrhage volume were significantly (P < .05) greater in the 1% EPA + DHA-fed rats than in other rats. Magnetic resonance imaging consistently showed that edema and bleeding were visible in only the rats fed 1% EPA + DHA. Levels of superoxide dismutase and glutathione were significantly (P < .05) lower in rats fed 0.5% and 1% EPA + DHA than those fed 0% EPA + DHA. Thiobarbituric acid-reactive substance content was significantly (P < .05) higher in 1% EPA + DHA-fed rats than in 0% and 0.5% EPA + DHA-fed rats. The level of 8-hydroxydeoxyguanosine was significantly (P < .05) higher in ICH rats with all diets than in sham surgery rats. Brain levels of EPA and DHA were highest in rats fed 1% EPA + DHA than in rats fed 0% and 0.5% EPA + DHA. These results suggested that intake of 1% EPA + DHA of total energy could lead to oxidative damage to the brain and thus increase the risk of intracerebral hemorrhagic stroke in this rat model.
Porsgaard, Trine; Overgaard, Julie; Krogh, Anne Louise; Jensen, Mette Behrmann; Guo, Zheng; Mu, Huiling
Many studies have shown beneficial effects of long chain n-3 polyunsaturated fatty acids (PUFA) on human health. Regardless of the positive effects of n-3 PUFA, the intake of these fatty acids remains low. An approach to increase the intake of n-3 PUFA in the population is to incorporate fish oil into food. In the present study, fish oil was incorporated into butter blends by enzymatic interesterification. The aim of the study was to investigate the effects of this butter product in comparison with a commercial butter blend and a product produced by interesterification but without fish oil. Golden Syrian hamsters received hamster feed blended with one of the three butter products. After 6 weeks of feeding, the fatty acid compositions of plasma, erythrocytes, liver, brain, and visceral fat were determined. The intake of butter product with fish oil resulted in a higher level of n-3 PUFA in plasma, erythrocytes, and liver. The incorporation of n-3 PUFA was significantly higher in phospholipids than in triacylglycerols. The results suggest that enriching butter blends with small amounts of fish oil can be used as an alternative method for improving the level of n-3 PUFA in biological tissues.
Smith, Scott M.; Mehta, Satish K.; Pierson, Duane L.; Zwart, Sara R.
Space flight has many negative effects on human physiology, including bone and muscle loss. These are some of the systems on which intakes of fish and n-3 fatty acids have positive effects. These effects are likely to occur through inhibition of inflammatory cytokines (such as TNFalpha) and thus inhibition of downstream NF-KB activation. We documented this effect in a 3D cell culture model, where NF-KB activation in osteoclasts was inhibited by eicosapentaenoic acid, an n-3 fatty acid. We have extended these studies and report here (a) NF-KB expression in peripheral blood mononuclear cells of Space Shuttle crews on 2-wk missions, (b) the effects of n-3 fatty acid intake after 60 d of bed rest (a weightlessness analog), and (c) the effects of fish intake in astronauts after 4 to 6 mo on the International Space Station. After Shuttle flights of 2 wk, NFKB p65 expression at landing was increased (P less than 0.001). After 60 d of bed rest, higher intake of n-3 fatty acids was associated with less N-telopeptide excretion (Pearson r = -0.62, P less than 0.05). Higher consumption of fish during flight was associated with higher bone mineral density (Pearson r = -0.46, P less than 0.05). Together with our earlier findings, these data provide mechanistic cellular and preliminary human evidence of the potential for n-3 fatty acids to counteract bone loss associated with spaceflight. This study was supported by the NASA Human Research Program.
Vauzour, David; Tejera, Noemi; O'Neill, Colette; Booz, Valeria; Jude, Baptiste; Wolf, Insa M.A.; Rigby, Neil; Silvan, Jose Manuel; Curtis, Peter J.; Cassidy, Aedin; de Pascual-Teresa, Sonia; Rimbach, Gerald; Minihane, Anne Marie
Increased tissue status of the long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) is associated with cardiovascular and cognitive benefits. Limited epidemiological and animal data suggest that flavonoids, and specifically anthocyanins, may increase EPA and DHA levels, potentially by increasing their synthesis from the shorter-chain n-3 PUFA, α-linolenic acid. Using complimentary cell, rodent and human studies we investigated the impact of anthocyanins and anthocyanin-rich foods/extracts on plasma and tissue EPA and DHA levels and on the expression of fatty acid desaturase 2 (FADS2), which represents the rate limiting enzymes in EPA and DHA synthesis. In experiment 1, rats were fed a standard diet containing either palm oil or rapeseed oil supplemented with pure anthocyanins for 8 weeks. Retrospective fatty acid analysis was conducted on plasma samples collected from a human randomized controlled trial where participants consumed an elderberry extract for 12 weeks (experiment 2). HepG2 cells were cultured with α-linolenic acid with or without select anthocyanins and their in vivo metabolites for 24 h and 48 h (experiment 3). The fatty acid composition of the cell membranes, plasma and liver tissues were analyzed by gas chromatography. Anthocyanins and anthocyanin-rich food intake had no significant impact on EPA or DHA status or FADS2 gene expression in any model system. These data indicate little impact of dietary anthocyanins on n-3 PUFA distribution and suggest that the increasingly recognized benefits of anthocyanins are unlikely to be the result of a beneficial impact on tissue fatty acid status. PMID:25573539
Dahlin, Maria; Hjelte, Lena; Nilsson, Susanne; Amark, Per
The ketogenic diet (KD) is used to treat medically refractory epilepsy in children. Alterations of fatty acid (FA) levels may reflect one mechanism of action. We examined the influence of the KD on FA levels and seizure control. The levels of 17 FAs in plasma phospholipids were determined before and 1, 3, 6, and 12 months after initiation of the KD in 25 children (mean age 6.3 years) with intractable epilepsy. Fluid omega-3 FA was supplemented in the diet after one month. Highly significant changes of the levels of several FAs were found. Linoleic acid (LA) and eicosapentaenoic acid (EPA) increased, whereas arachidonic acid (AA) and Mead acid (20:3 n-9) decreased. Docosahexaenoic acid (DHA) increased insignificantly. However, no correlation of changes in FA levels with seizure response was found. The ratio of omega-6 to omega-3 gradually decreased from 7.0 before to 4.9 at 12 months after starting the diet, presumably a cardiovascular benefit. The composition of the KD differs as to FA content and type between different treating centers but, still, the efficacy reports are very similar. This study demonstrates the possibility of composing the KD in such a way that the FA profile is kept within a normal range, which may reduce cardiovascular risks.
Castro-González, María Isabel; Ojeda, Anayté; Silencio, José Luis; Cassis, Lorena; Ledesma, Hector; Pérez-Gil, Fernando
The aim of this study was to characterize and to evaluate the lipidic composition of mexican marine fishes with special emphasis in n-3 fatty acids as nutraceuticals. The edible portion of 25 species: humidity (H), crude protein (CP), total lipids (TL) and fatty acids (FA). The average content (g/100g edible portion) of H was 75.20, PC was 18.40, TL was 3.60. Four n-3 FA were identified in all the samples and they were found in the next abundance order (mg/100g edible portion): C22:6n-3 (DHA)(229.60), C20:5 n-3 (EPA)(52.10), C18:3 n-3 (ALA)(11.80) and C20:3 n-3 (2.25). By their origin and climate there were no difference. By their biologycal classification, n-3 FA content was higher in bony fishes than cartilaginous fishes. It was detected a proportional relation with the n-3 FA concentration and total lipid content. According to their ecotic distribution there were numerical differences in DHA content (mg/100g edible portion) between pelagics (420.70), benthopelagics (125.30) and demersals fishes (225.40). Fatty fishes had higher content of EPA and DHA (mg/100g edible portion) (109.27 and 552.72) than semifatty fishes (56.12 and 226.29) and leanness (15.95 and 96.52), respectively. Bony, fatty and pelagic fishes had a higher content of EPA+DHA. According with the international recommendation values (200 to 600 mg EPA+DHA/day) the 44% of the analyzed species could be considered as functional foods due to their high content of EPA + DHA in a range of 220 to 1300 mg/100g.
Al Mamun, Abdullah; Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Tsuchikura, Satoru; Hossain, Shahdat; Shido, Osamu
The effects of cholesterol-lowering statins, which substantially benefit future cardiovascular events, on fatty acid metabolism have remained largely obscured. In this study, we investigated the effects of atorvastatin on fatty acid metabolism together with the effects of TAK-085 containing highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl ester on atorvastatin-induced n-3 polyunsaturated fatty acid lowering in SHR.Cg-Lepr(cp)/NDmcr (SHRcp) rats, as a metabolic syndrome model. Supplementation with 10mg/kg body weight/day of atorvastatin for 17 weeks significantly decreased plasma total cholesterol and very low density lipoprotein cholesterol. Atorvastatin alone caused a subtle change in fatty acid composition particularly of EPA and DHA in the plasma, liver or erythrocyte membranes. However, the TAK-085 consistently increased both the levels of EPA and DHA in the plasma, liver and erythrocyte membranes. After confirming the reduction of plasma total cholesterol, 300mg/kg body weight/day of TAK-085 was continuously administered for another 6 weeks. Supplementation with TAK-085 did not decrease plasma total cholesterol but significantly increased the EPA and DHA levels in both the plasma and liver compared with rats administered atorvastatin only. Supplementation with atorvastatin alone significantly decreased sterol regulatory element-binding protein-1c, Δ5- and Δ6-desaturases, elongase-5, and stearoyl-coenzyme A (CoA) desaturase-2 levels and increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA expression in the liver compared with control rats. TAK-085 supplementation significantly increased stearoyl-CoA desaturase-2 mRNA expression. These results suggest that long-term supplementation with atorvastatin decreases the EPA and DHA levels by inhibiting the desaturation and elongation of n-3 fatty acid metabolism, while TAK-085 supplementation effectively replenishes this effect in SHRcp rat liver.
Trépanier, Marc-Olivier; Hopperton, Kathryn E; Orr, Sarah K; Bazinet, Richard P
Neuroinflammation is a characteristic of a multitude of neurological and psychiatric disorders. Modulating inflammatory pathways offers a potential therapeutic target in these disorders. Omega-3 polyunsaturated fatty acids have anti-inflammatory and pro-resolving properties in the periphery, however, their effect on neuroinflammation is less studied. This review summarizes 61 animal studies that tested the effect of omega-3 polyunsaturated fatty acids on neuroinflammatory outcomes in vivo in various models including stroke, spinal cord injury, aging, Alzheimer's disease, Parkinson's disease, lipopolysaccharide and IL-1β injections, diabetes, neuropathic pain, traumatic brain injury, depression, surgically induced cognitive decline, whole body irradiation, amyotrophic lateral sclerosis, N-methyl-D-aspartate-induced excitotoxicity and lupus. The evidence presented in this review suggests anti-neuroinflammatory properties of omega-3 polyunsaturated fatty acids, however, it is not clear by which mechanism omega-3 polyunsaturated fatty acids exert their effect. Future research should aim to isolate the effect of omega-3 polyunsaturated fatty acids on neuroinflammatory signaling in vivo and elucidate the mechanisms underlying these effects.
Breast cancer risk is associated with dietary fat intake. Omega-6 fatty acids (n6) promote while omega-3 fatty acids (n3) inhibit tumorigenesis. Increased sex hormone (SH) concentrations are associated with risk of breast cancer. The effects of total fat and n3 on SH and PLFA were assessed in a f...
Maximin, Elise; Langelier, Bénédicte; Aïoun, Josiane; Al-Gubory, Kaïs H; Bordat, Christian; Lavialle, Monique; Heberden, Christine
Fatty acid binding protein 7 (FABP7), abundant in the embryonic brain, binds with the highest affinity to docosahexaenoic acid (DHA) and is expressed in the early stages of embryogenesis. Here, we have examined the consequences of the exposure to different DHA levels and of the in utero depletion of FABP7 on early rat brain development. Neurodevelopment was evaluated through the contents of two proteins, connexin 43 (Cx43) and cyclin-dependent kinase 5 (CDK5), both involved in neuroblast proliferation, differentiation, and migration. The dams were fed with diets presenting different DHA contents, from deficiency to supplementation. DHA brain embryos contents already differed at embryonic day 11.5 and the differences kept increasing with time. Cx43 and CDK5 contents were positively associated with the brain DHA levels. When FABP7 was depleted in vivo by injections of siRNA in the telencephalon, the enhancement of the contents of both proteins was lost in supplemented animals, but FABP7 depletion did not modify phospholipid compositions regardless of the diets. Thus, FABP7 is a necessary mediator of the effect of DHA on these proteins synthesis, but its role in DHA uptake is not critical, although FABP7 is localized in phospholipid-rich areas. Our study shows that high contents of DHA associated with FABP7 are necessary to promote early brain development, which prompted us to recommend DHA supplementation early in pregnancy.
MacDonald-Wicks, Lesley K; Garg, Manohar L
The health benefits of long-chain n-3 PUFA (20:5n-3 and 22:6n-3) depend on the extent of incorporation of these FA into plasma and tissue lipids. This study aimed to investigate the effect of the background dietary fat (saturated, monounsaturated, or n-6 polyunsaturated) on the quantitative incorporation of dietary 18:3n-3 and its elongated and desaturated products into the plasma and the liver lipids of rats. Female weanling Wistar rats (n = 54) were randomly assigned to six diet groups (n = 9). The fat added to the semipurified diets was tallow (SFA), tallow plus linseed oil (SFA-LNA), sunola oil (MUFA), sunola oil plus linseed oil (MUFA-LNA), sunflower oil (PUFA), or sunflower oil plus linseed oil (PUFA-LNA). At the completion of the 4-wk feeding period, quantitative FA analysis of the liver and plasma was undertaken by GC. The inclusion of linseed oil in the rat diets increased the level of 18:3n-3, 20:5n-3, and, to a smaller degree, 22:6n-3 in plasma and liver lipids regardless of the background dietary fat. The extent of incorporation of 18:3n-3, 20:5n-3, and 22:5n-3 followed the order SFA-LNA > MUFA-LNA > PUFA-LNA. Levels of 22:6n-3 were increased to a similar extent regardless of the type of major fat in the rat diets. This indicates that the background diet affects the incorporation in liver and plasma FA pools of the n-3 PUFA with the exception of 22:6n-3 and therefore the background diet has the potential to influence the already established health benefits of long-chain n-3 fatty acids.
Algamas-Dimantov, Anna; Yehuda-Shnaidman, Einav; Hertz, Rachel; Peri, Irena; Bar-Tana, Jacob; Schwartz, Betty
The global obesity / diabetes epidemic has resulted in robust increase in the incidence of colorectal cancer (CRC). Epidemiological, animal and human studies have indicated efficacy of (n-3) PUFA in chemoprevention of sporadic and genetic-driven CRC. However, diabetes-promoted CRC presents a treatment challenge that surpasses that of sporadic CRC. This report analyzes the efficacy of (n-3) PUFA generated by the fat-1 transgene that encodes an (n-6) to (n-3) PUFA desaturase, and of synthetic (n-3) PUFA mimetic (MEDICA analog), to suppress CRC development in carcinogen-induced diabetes-promoted animal model. Carcinogen-induced CRC is shown here to be promoted by the diabetes context, in terms of increased aberrant crypt foci (ACF) load, cell proliferation and epithelial dedifferentiation, being accompanied by increase in the expression of HNF4α, β-catenin, and β-catenin-responsive genes. Incorporating the fat-1 transgene in the diabetes context, or oral MEDICA treatment, resulted in ameliorating the diabetic phenotype and in abrogating CRC, with decrease in ACF load, cell proliferation and the expression of HNF-4α, β-catenin, and β-catenin-responsive genes. The specificity of (n-3) PUFA in abrogating CRC development, as contrasted with enhancing CRC by (n-6) PUFA, was similarly verified in CRC cell lines. These findings may indicate prospective therapeutic potential of (n-3) PUFA or MEDICA in the management of CRC, in particular diabetes-promoted CRC.
Stamey, J A; Shepherd, D M; de Veth, M J; Corl, B A
Fish oil is used as a ration additive to provide n-3 fatty acids to dairy cows. Fish do not synthesize n-3 fatty acids; they must consume microscopic algae or other algae-consuming fish. New technology allows for the production of algal biomass for use as a ration supplement for dairy cattle. Lipid encapsulation of the algal biomass protects n-3 fatty acids from biohydrogenation in the rumen and allows them to be available for absorption and utilization in the small intestine. Our objective was to examine the use of algal products as a source for n-3 fatty acids in milk. Four mid-lactation Holsteins were assigned to a 4×4 Latin square design. Their rations were supplemented with 1× or 0.5× rumen-protected (RP) algal biomass supplement, 1× RP algal oil supplement, or no supplement for 7 d. Supplements were lipid encapsulated (Balchem Corp., New Hampton, NY). The 1× supplements provided 29 g/d of docosahexaenoic acid (DHA), and 0.5× provided half of this amount. Treatments were analyzed by orthogonal contrasts. Supplementing dairy rations with rumen-protected algal products did not affect feed intake, milk yield, or milk component yield. Short- and medium-chain fatty acid yields in milk were not influenced by supplements. Both 0.5× and 1× RP algae supplements increased daily milk fat yield of DHA (0.5 and 0.6±0.10 g/d, respectively) compared with 1× RP oil (0.3±0.10 g/d), but all supplements resulted in milk fat yields greater than that of the control (0.1±0.10g/d). Yield of trans-18:1 fatty acids in milk fat was also increased by supplementation. Trans-11 18:1 yield (13, 20, 27, and 15±3.0 g/d for control, 0.5× RP algae, 1× RP algae, and 1× RP oil, respectively) was greater for supplements than for control. Concentration of DHA in the plasma lipid fraction on d 7 showed that the DHA concentration was greatest in plasma phospholipid. Rumen-protected algal biomass provided better DHA yield than algal oil. Feeding lipid-encapsulated algae supplements
Ramsden, Christopher E; Faurot, Keturah R; Zamora, Daisy; Suchindran, Chirayath M; Macintosh, Beth A; Gaylord, Susan; Ringel, Amit; Hibbeln, Joseph R; Feldstein, Ariel E; Mori, Trevor A; Barden, Anne; Lynch, Chanee; Coble, Rebecca; Mas, Emilie; Palsson, Olafur; Barrow, David A; Mann, J Douglas
Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month, and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in highly unsaturated fatty acids (HUFA) score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives. Fifty-six of 67 patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (-7.5 vs -2.1; P<0.001) and the number of Headache Days per month (-8.8 vs -4.0; P=0.02), compared to the L6 group. The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (-4.6 vs -1.2; P=0.01) and the n-6 in HUFA score (-21.0 vs -4.0%; P<0.001), and greater increases in antinociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs +61.1%; P<0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs +27.2; P<0.001). A dietary intervention increasing n-3 and reducing n-6 fatty acids reduced headache pain, altered antinociceptive lipid mediators, and improved quality-of-life in this population.
Griffo, E; Di Marino, L; Patti, L; Bozzetto, L; Annuzzi, G; Cipriano, P; Mangione, A; Della Pepa, G; Cocozza, S; Riccardi, G; Rivellese, A A
Postprandial lipid abnormalities are considered an independent cardiovascular risk factor. Hence, it is important to find nutritional strategies that are able to positively influence these abnormalities. Since the effect of n-3 polyunsaturated fatty acids (PUFA) and polyphenols on postprandial lipids in humans is still under debate, we evaluated the acute response of triglyceride-rich lipoproteins to test meals that are naturally rich in polyphenols and/or marine long-chain (LC) n-3 PUFAs. We hypothesized that LC n-3 PUFA would have a different effect on chylomicron and very low density lipoproteins when compared with polyphenols or their combination. We randomly assigned 78 individuals who were at high cardiometabolic risk to 4 isoenergetic diets. These diets only differed in amount of LC n-3 PUFA and/or polyphenols. Prior to starting the intervention, each subject underwent a test meal similar to the type of diet assigned: low in LC n-3 PUFA and polyphenols (control), rich in LC n-3 PUFA and low in polyphenols, rich in polyphenols and low in LC n-3 PUFA, or rich in both. Blood samples were taken before and up to 6 hours after the test meal in order to evaluate cholesterol and triglycerides (plasma and triglyceride-rich lipoprotein), apolipoprotein B-48 (large very low density lipoprotein), glucagon-like peptide-1, and free fatty acid plasma levels. The levels of chylomicron cholesterol and triglyceride in response to the test meal rich in LC n-3 PUFA were significantly higher than after the control meal (P = .037 and P = .018); there was no difference in the other variables. In conclusion, this study indicates that acute administration of marine LC n-3 PUFA increases postprandial chylomicron response in contrast with their lowering chronic effects. These differences underline the importance of understanding the acute and chronic effects of nutritional, as well as of other types of, interventions.
Sekikawa, Akira; Steingrimsdottir, Laufey; Ueshima, Hirotsugu; Shin, Chol; Curb, J. David; Evans, Rhobert W.; Hauksdottir, Alda M.; Kadota, Aya; Choo, Jina; Masaki, Kamal; Thorsson, Bolli; Launer, Lenore J.; Garcia, Melisa E.; Maegawa, Hiroshi; Willcox, Bradley J.; Eiriksdottir, Gudny; Fujiyoshi, Akira; Miura, Katsuyuki; Harris, Tamara B.; Kuller, Lewis H.; Gudnason, Vilmundur
Summary In the 1990’s Iceland and Japan were known as countries with high fish consumption whereas coronary heart disease (CHD) mortality in Iceland was high and that in Japan was low among developed countries. We described recent data fish consumption and CHD mortality from publicly available data. We also measured CHD risk factors and serum levels of marine-derived n-3 and other fatty acids from population-based samples of 1,324 men in Iceland, Japan, South Korea, and the US. CHD mortality in men in Iceland was almost 3 times as high as that in Japan and South Korea. Generally a profile of CHD risk factors in Icelanders compared to Japanese was more favorable. Serum marine-derived n-3 fatty acids in Iceland were significantly lower than in Japan and South Korea but significantly higher than in the US. PMID:22658580
Delarue, Jacques; Guriec, Nathalie
Health benefits or advocated health benefits of long-chain (LC) n-3 PUFA are better known by medical doctors as well as by consumers, so that consumption increases. In addition, the development of aquaculture requires more fishmeal and fish oil. Humanisation of care of companion animals is also associated with addition of LC n-3 PUFA in pet foods. The risk of the increased demand for LC n-3 PUFA is the excess harvesting of natural sources, especially of marine origin (oily fishes, krill). In order to improve sustainability, alternative sources of LC n-3 PUFA have been developed. These alternative sources are: (a) terrestrial plants naturally or genetically enriched in stearidonic acid (SDA), which bypasses the first limiting step of (i.e. ∆6 desaturase) of the biosynthesis of LC n-3 PUFA; (b) single-cell oils rich in LC n-3 PUFA (microalgae, Escherichia coli) and krill. Currently, plants rich in SDA are expensive, metabolic engineering is unfavourably accepted by consumers in many countries, cultivation of microalgae is very expensive even though their ability (for some of them) to synthesise biofuels could induce a decrease in industrial costs, and Antarctic krill harvest must be restricted. Thus, it is difficult to predict their real development in the future.
Nakamoto, Kazuo; Obata, Tokio; Hirasawa, Akira; Kim, Ke Ih; Kim, Soo Ryang; Tokuyama, Shogo
Nonalcoholic fatty liver disease (NAFLD) is characterized by the pathological accumulation of fat in the liver in the absence of any other disease related to liver steatosis, which includes a wide spectrum of liver diseases ranging from mild asymptomatic fatty liver to nonalcoholic steatohepatitis (NASH) and cirrhosis. Recently, it was reported that NAFLD is characterized by the impaired bioavailability of liver n-6 and n-3 long-chain polyunsaturated fatty acids (PUFAs). That is, compared with healthy individuals, steatosis and steatohepatitis patients have higher n-6/n-3 PUFA ratios. Furthermore, per recent research, decreasing the intake of total fats and increasing the intake of n-3 PUFAs may be beneficial in the treatment of NAFLD. In contrast, some reports describe that NASH patients have more metabolic abnormalities than NAFLD patients; however, these are not influenced by dietary fatty acids. Thus, at present, various opinions exist regarding the efficacy of n-3 PUFA in the treatment of NAFLD. In this review, we discuss the considerable interest n-3 PUFA has attracted as a potential treatment for NAFLD.
Allen, P C; Danforth, H D; Levander, O A
Four experiments were run in which diets incorporating various levels of n-3 fatty acids (n-3FA) from fish (menhaden) oil or flax seed were tested for their abilities to reduce the severity of Eimeria tenella infections in young broiler chicks. The diets were fed from 1 d of age through 3 wk of age. Chickens were infected at 2 wk of age. Diets consisting of broiler starter ration supplemented with 2.5 to 10% fish oil, 10% flax seed oil, or 10% linseed oil significantly decreased cecal lesions and maintained weight gains as compared to unsupplemented diets. Light micrographs of ceca from chickens that consumed high n-3FA diets showed reduced parasite invasion and development. Short-term feeding of diets high in n-3FA to young chicks may be a practical method for reducing production losses from cecal coccidiosis.
Vancassel, S; Blondeau, C; Lallemand, S; Cador, M; Linard, A; Lavialle, M; Dellu-Hagedorn, F
Inattention, hyperactivity and impulsiveness are the main symptoms of the heterogeneous attention-deficit/hyperactivity disorder (ADHD). It has been suggested that ADHD is associated with an imbalance in polyunsaturated fatty acid (PUFA) composition, with abnormal low levels of the main n-3 PUFA, DHA (22: 6n-3). DHA is highly accumulated in nervous tissue membranes and is implicated in neural function. Animal studies have shown that diet-induced lack of DHA in the brain leads to alterations in cognitive processes, but the relationship between DHA and hyperactivity is unclear. We examined the membrane phospholipid fatty acid profile in frontal cortex of rats characterized for attention, impulsiveness and motricity in various environmental contexts to determine the relationship between brain PUFA composition and the symptoms of ADHD. The amounts of n-3 PUFA in the PE were significantly correlated with nocturnal locomotor activity and the locomotor response to novelty: hyperactive individuals had less n-3 PUFA than hypoactive ones. We conclude that spontaneous hyperactivity in rats is the symptom of ADHD that best predicts the n-3 PUFA content of the frontal cortex. This differential model in rats should help to better understand the role of PUFA in several psychopathologies in which PUFA composition is modified.
Ruxton, C H S; Calder, P C; Reed, S C; Simpson, M J A
A considerable literature has been published on the health benefits of fish, oil-rich fish and fish oils and their constituent long-chain (LC) n-3 PUFA. Evidence from epidemiological studies highlights the cardioprotective attributes of diets rich in fish, especially oil-rich fish. Data from intervention trials are consistent in suggesting that LC n-3 PUFA lower the risk of CVD, probably by the multiple mechanisms of lowering serum triacylglycerols, improving the LDL:HDL ratio, anti-arrhythmic effects on heart muscle, improved plaque stability, anti-thrombotic effects and reduced endothelial activation. Research indicates LC n-3 PUFA provision has an impact during development, and there is preliminary evidence that docosahexaenoic acid supplementation during pregnancy could optimise brain and retina development in the infant. LC n-3 PUFA are also postulated to ameliorate behavioural and mental health disturbances such as depression, schizophrenia, dementia and attention deficit hyperactivity disorder. However, despite some positive evidence in each of these areas, use of LC n-3 PUFA in these conditions remains at the experimental stage. In the case of immune function, there is little doubt that LC n-3 PUFA have a positive effect. Although intervention trials in rheumatoid arthritis show strong evidence of benefit, evidence for efficacy in other inflammatory conditions, including Crohn's disease, ulcerative colitis, psoriasis, lupus, multiple sclerosis, cystic fibrosis and asthma, is inconsistent or inadequate. More promising evidence in some conditions may come from studies which attempt to modify the fetal environment using LC n-3 PUFA supplementation during pregnancy.
Anderson, Gregory J; Neuringer, Martha; Lin, Don S; Connor, William E
Our previous studies of rhesus monkeys showed that combined prenatal and postnatal n-3 fatty acid deficiency resulted in reduced visual acuity, abnormal retinal function, and low retina and brain docosahexaenoic acid content. We now report effects of n-3 fatty acid deficiency during intrauterine development only. Rhesus infants, born to mothers fed an n-3 fatty acid deficient diet throughout pregnancy, were repleted with a diet high in alpha-linolenic acid from birth to 3 y. Fatty acid composition was determined for plasma and erythrocytes at several time points, for prefrontal cerebral cortex biopsies at 15, 30, 45, and 60 wk, and for cerebral cortex and retina at 3 y. Visual acuity was determined behaviorally at 4, 8, and 12 postnatal weeks, and the electroretinogram was recorded at 3-4 mo. Total n-3 fatty acids were reduced by 70-90% in plasma, erythrocytes, and tissues at birth but recovered to control values within 4 wk in plasma, 8 wk in erythrocytes, and 15 wk in cerebral cortex. At 3 y, fatty acid composition was normal in brain phospholipids, but in the retina DHA recovery was incomplete (84% of controls). Visual acuity thresholds did not differ from those of control infants from mothers fed a high linolenic acid diet. However, the repleted group had lower amplitudes of cone and rod ERG a-waves. These data suggest that restriction of n-3 fatty acid intake during the prenatal period may have long-term effects on retinal fatty acid composition and function.
Hamazaki, K; Harauma, A; Otaka, Y; Moriguchi, T; Inadera, H
N-3 polyunsaturated fatty acids (PUFAs), especially long-chain types such as docosahexaenoic acid, are important nutrients in pregnancy, but the relationship between n-3 PUFA levels and perinatal and postnatal depression remains controversial. This study examined the possible relationship between serum n-3 PUFA levels and psychological distress among expectant mothers in early pregnancy. Data and specimen samples were obtained in a birth cohort study started at Toyama Regional Center in July 2012 as an adjunct study of the Japan Environment and Children's Study. Blood samples were collected at 9-14 weeks' gestation (75% of samples) or after 15 weeks (25%). Subjects with a Kessler Psychological Distress Scale score (K6) ⩾ 9 were assigned to the psychological distress group (n=283). The control group (n=283) was matched for age, educational level and family income. Fatty acid composition was determined from serum samples by gas chromatography. Associations between fatty acid levels and incident psychological distress were evaluated by logistic regression. After adjusting for possible confounders, eicosapentaenoic acid showed an inverse association with risk of psychological distress, with an odds ratio of 0.47 (95% confidence interval: 0.30, 0.73) for the highest tertile. This inverse association remained even after applying a higher cutoff score (K6 ⩾ 13) indicating severe psychological distress (74 pairs). We believe this is the first study to reveal the associations between serum n-3 PUFAs and risk of psychological distress in early pregnancy. Further research is required to verify the causality of these associations.
Hamazaki, K; Harauma, A; Otaka, Y; Moriguchi, T; Inadera, H
N-3 polyunsaturated fatty acids (PUFAs), especially long-chain types such as docosahexaenoic acid, are important nutrients in pregnancy, but the relationship between n-3 PUFA levels and perinatal and postnatal depression remains controversial. This study examined the possible relationship between serum n-3 PUFA levels and psychological distress among expectant mothers in early pregnancy. Data and specimen samples were obtained in a birth cohort study started at Toyama Regional Center in July 2012 as an adjunct study of the Japan Environment and Children's Study. Blood samples were collected at 9–14 weeks' gestation (75% of samples) or after 15 weeks (25%). Subjects with a Kessler Psychological Distress Scale score (K6) ⩾9 were assigned to the psychological distress group (n=283). The control group (n=283) was matched for age, educational level and family income. Fatty acid composition was determined from serum samples by gas chromatography. Associations between fatty acid levels and incident psychological distress were evaluated by logistic regression. After adjusting for possible confounders, eicosapentaenoic acid showed an inverse association with risk of psychological distress, with an odds ratio of 0.47 (95% confidence interval: 0.30, 0.73) for the highest tertile. This inverse association remained even after applying a higher cutoff score (K6 ⩾13) indicating severe psychological distress (74 pairs). We believe this is the first study to reveal the associations between serum n-3 PUFAs and risk of psychological distress in early pregnancy. Further research is required to verify the causality of these associations. PMID:26882037
Husted, Kristian Søborg; Bouzinova, Elena V
This review aims to clarify the relation between the ratio of omega-6 to omega-3 fatty acids and the development of depression. It is explained how these fatty acids are involved in the production of eicosanoids and how these fatty acids can affect the membrane fluidity, by their incorporation into membrane phospholipids. In addition, it is described how omega-3 derivatives are shown to regulate gene transcription. In view of the pathophysiology of depression, the mechanisms of how an altered ratio of omega-6 to omega-3 could be involved in depression are discussed. Possible mechanisms could include an increased production of pro-inflammatory cytokines, which can activate the HPA axis and a changed membrane fluidity, which potentially affects membrane bound enzymes, ion channels, receptor activity and neurotransmitter binding. In view of clinical trials, it is also discussed whether omega-3 supplementation could have a beneficial effect in the treatment of depressive patient. There are strong indications that an increased ratio of membrane omega-6 to omega-3 is involved in the pathogenesis of depression and so far, omega-3 supplementation has shown positive effects in clinical trials.
Zakaria, Md. Zuki Abu Bakar; Meng, Goh Yong; Sazili, Awis Qurni
The effects of feeding different levels of whole linseed on fatty acid (FA) composition of muscles and adipose tissues of goat were investigated. Twenty-four Crossed Boer bucks were assigned randomly into three treatment diets: L0, L10, or L20, containing 0%, 10%, or 20% whole linseed, respectively. The goats were slaughtered after 110 days of feeding. Samples from the longissimus dorsi, supraspinatus, semitendinosus, and subcutaneous fat (SF) and perirenal fat (PF) were taken for FA analyses. In muscles, the average increments in α-linolenic (ALA) and total n-3 PUFA were 6.48 and 3.4, and 11.48 and 4.78 for L10 and L20, respectively. In the adipose tissues, the increments in ALA and total n-3 PUFA were 3.07- and 6.92-fold and 3.00- and 7.54-fold in SF and PF for L10 and L20, respectively. The n-6 : n-3 ratio of the muscles was decreased from up to 8.86 in L0 to 2 or less in L10 and L20. The PUFA : SFA ratio was increased in all the tissues of L20 compared to L0. It is concluded that both inclusion levels (10% and 20%) of whole linseed in goat diets resulted in producing meat highly enriched with n-3 PUFA with desirable n-6 : n-3 ratio. PMID:25478601
Skoch, Antonín; Tošner, Zdeněk; Hájek, Milan
In this study, we present a method for the detection of n-3 fatty acid (n-3 FA) signals using MRS in adipose tissue in vivo. This method (called oMEGA-PRESS) is based on the selective detection of the CH3 signal of n-3 FA using the MEGA-PRESS (MEshcher-GArwood Point-RESolved Spectroscopy) J-difference editing technique. We optimized the envelope shape and frequency of spectral editing pulses to minimize the spurious co-editing and incomplete subtraction of the CH3 signal of other FAs, which normally obscure the n-3 FA CH3 signal in MR spectra acquired using standard PRESS techniques. The post-processing of the individual data scans with the phase and frequency correction before data subtraction and averaging was implemented to further improve the quality of in vivo spectra. The technique was optimized in vitro on lipid phantoms using various concentrations of n-3 FA and examined in vivo at 3 T on 15 healthy volunteers. The proportion of n-3 FA estimated by the oMEGA-PRESS method in phantoms showed a highly significant linear correlation with the n-3 FA content determined by gas chromatography. The signal attributed to n-3 FA was observed in all subjects. Comparisons with the standard PRESS technique revealed an enhanced identification of the n-3 FA signal using oMEGA-PRESS. The presented method may be useful for the non-invasive quantification of n-3 FA in adipose tissue, and could aid in obtaining a better understanding of various aspects of n-3 FA metabolism.
Feng, Ruibing; Wang, Meng; Yan, Chunyan
n-3 polyunsaturated fatty acids (PUFAs) are beneficial for numerous models of liver diseases. The probable protective effects of n-3 PUFA against carbon-tetrachloride- (CCl4-) induced acute liver injury were evaluated in a fat-1 transgenic mouse that synthesizes endogenous n-3 from n-6 PUFA. Fat-1 mice and their WT littermates were fed a modified AIN93 diet containing 10% corn oil and were injected intraperitoneally with a single dose of CCl4 or vehicle. CCl4 challenge caused severe liver injury in WT mice, as indicated by serum parameters and histopathological changes, which were remarkably ameliorated in fat-1 mice. Endogenous n-3 PUFA decreased the elevation of oxidative stress induced by CCl4 challenge, which might be attributed to the activation of Nrf2/keap1 pathway. Additionally, endogenous n-3 PUFA reduces hepatocyte apoptosis via suppressing MAPK pathway. These findings indicate that n-3 PUFA has potent protective effects against acute liver injury induced by CCl4 in mice, suggesting that n-3 PUFA can be used for the prevention and treatment of liver injury. PMID:27891208
Conde-Sieira, Marta; Bonacic, Kruno; Velasco, Cristina; Valente, Luisa M P; Morais, Sofia; Soengas, José L
We assessed the presence of fatty acid (FA)-sensing mechanisms in hypothalamus of Senegalese sole (Solea senegalensis) and investigated their sensitivity to FA chain length and/or level of unsaturation. Stearate (SA, saturated FA), oleate (OA, monounsaturated FA of the same chain length), α-linolenate [ALA, a n-3 polyunsaturated fatty acid (PUFA) of the same chain length], and eicosapentanoate (EPA, a n-3 PUFA of a larger chain length) were injected intraperitoneally. Parameters related to FA sensing and neuropeptide expression in the hypothalamus were assessed after 3 h and changes in accumulated food intake after 4, 24, and 48 h. Three FA sensing systems characterized in rainbow trout were also found in Senegalese sole and were activated by OA in a way similar to that previously characterized in rainbow trout and mammals. These hypothalamic FA sensing systems were also activated by ALA, differing from mammals, where n-3 PUFAs do not seem to activate FA sensors. This might suggest additional roles and highlights the importance of n-3 PUFA in fish diets, especially in marine species. The activation of FA sensing seems to be partially dependent on acyl chain length and degree of saturation, as no major changes were observed after treating fish with SA or EPA. The activation of FA sensing systems by OA and ALA, but not SA or EPA, is further reflected in the expression of hypothalamic neuropeptides involved in the control of food intake. Both OA and ALA enhanced anorexigenic capacity compatible with the activation of FA sensing systems.
Spahis, S; Alvarez, F; Dubois, J; Ahmed, N; Peretti, N; Levy, E
Non-alcoholic fatty liver disease (NAFLD) represents one of the most common causes of liver disease worldwide. As the NAFLD pathogenesis is associated with diet and lifestyle, the aims of the present work are to assess fatty acid (FA) composition in NAFLD young French-Canadian, to determine whether treatment with n-3 FA improves the plasma FA profile, and to define the time on the effectiveness of n-3 FA supplementation. Baseline characteristics of the NAFLD subjects show increased, anthropometric and biochemical parameters. Their plasma FA composition is characterized by a percent increase in total n-6 FA and a high proportion of saturated and total monounsaturated FA, as well as a decrease in Δ5 and increase in Δ6 desaturases. In conclusion, our results document for the first time the composition of plasma FAs in NAFLD young French Canadian and the efficacy of 3-month supplementation to improve the proportion of n-3 FA in their plasma.
Rincón-Cervera, Miguel Ángel; Valenzuela, Rodrigo; Hernandez-Rodas, María Catalina; Barrera, Cynthia; Espinosa, Alejandra; Marambio, Macarena; Valenzuela, Alfonso
Alpha-linolenic acid (C18:3 n-3, ALA) is an essential fatty acid and the metabolic precursor of long-chain polyunsaturated fatty acids (LCPUFA) from the n-3 family with relevant physiological and metabolic roles: eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA). Western diet lacks of suitable intake of n-3 LCPUFA and there are recommendations to increase the dietary supply of such nutrients. Seed oils rich in ALA such as those from rosa mosqueta (Rosa rubiginosa), sacha inchi (Plukenetia volubis) and chia (Salvia hispanica) may constitute an alternative that merits research. This study evaluated hepatic and epididymal accretion and biosynthesis of n-3 LCPUFA, the activity and expression of Δ-5 and Δ-6 desaturase enzymes, the expression and DNA-binding activity of PPAR-α and SREBP-1c, oxidative stress parameters and the activity of antioxidative enzymes in rats fed sunflower oil (SFO, 1% ALA) as control group, canola oil (CO, 10% ALA), rosa mosqueta oil (RMO, 33% ALA), sacha inchi oil (SIO, 49% ALA) and chia oil (ChO, 64% ALA) as single lipid source. A larger supply of ALA increased the accretion of n-3 LCPUFA, the activity and expression of desaturases, the antioxidative status, the expression and DNA-binding of PPAR-α, the oxidation of fatty acids and the activity of antioxidant enzymes, whereas the expression and DNA-binding activity of SREBP-1c transcription factor and the biosynthetic activity of fatty acids declined. Results showed that oils rich in ALA such as SIO and ChO may trigger metabolic responses in rats such as those produced by n-3 PUFA.
Danthiir, Vanessa; Hosking, Diane; Burns, Nicholas R; Wilson, Carlene; Nettelbeck, Ted; Calvaresi, Eva; Clifton, Peter; Wittert, Gary A
Higher n-3 (ω-3) polyunsaturated fatty acids (PUFAs) and fish intake may help maintain cognitive function in older age. However, evidence is inconsistent; few studies have examined the relation in cognitively healthy individuals across numerous cognitive domains, and none to our knowledge have considered lifetime fish intake. We examined associations between multiple domains of cognition and erythrocyte membrane n-3 PUFA proportions and historical and contemporary fish intake in 390 normal older adults, analyzing baseline data from the Older People, Omega-3, and Cognitive Health trial. We measured n-3 PUFA in erythrocyte membranes, and we assessed historical and contemporary fish intake by food-frequency questionnaires. We assessed cognitive performance on reasoning, working memory, short-term memory, retrieval fluency, perceptual speed, simple/choice reaction time, speed of memory-scanning, reasoning speed, inhibition, and psychomotor speed. Cognitive outcomes for each construct were factor scores from confirmatory factor analysis. Multiple linear regression models controlled for a number of potential confounding factors, including age, education, sex, apolipoprotein E-ε 4 allele, physical activity, smoking, alcohol intake, socioeconomic variables, and other health-related variables. Higher erythrocyte membrane eicosapaentonoic acid proportions predicted slower perceptual and reasoning speed in females, which was attenuated once current fish intake was controlled. No other associations were present between n-3 PUFA proportions and cognitive performance. Higher current fish consumption predicted worse performance on several cognitive speed constructs. Greater fish consumption in childhood predicted slower perceptual speed and simple/choice reaction time. We found no evidence to support the hypothesis that higher proportions of long-chain n-3 fatty acids or fish intake benefits cognitive performance in normal older adults.
Rousseau, D; Moreau, D; Raederstorff, D; Sergiel, J P; Rupp, H; Muggli, R; Grynberg, A
Epidemiological studies suggest that n-3 polyunsaturated fatty acids (PUFA) are involved in the prevention of cardiovascular disease. Stress is known to increase the incidence of CVD and the present study was realised to evaluate some physiological and biochemical effects of dietary docosahexaenoic acid (DHA) in male Wistar rats subjected to a psycho social stress. Rats were fed for 8 weeks a semi-purified diet containing 10% of either sunflower seed oil or the same oil supplemented with DHA. This food supply represented 50% of their daily requirement. The remaining 50% were supplied as 45 mg food pellets designed to induce stress in rats by an intermittent-feeding schedule process. The control group (n = 12) was fed the equivalent food ration as a single daily feeding. The physiological cardiovascular parameters were recorded by telemetry through a transmitter introduced in the abdomen. At the end of the experimentation, the heart and adrenals were withdrawn and the fatty acid composition and the catecholamine store were determined. Dietary DHA induced a pronounced alteration of the fatty acid profile of cardiac phospholipids (PL). The level of all the n-6 PUFAs was reduced while 22:6 n-3 was increased. The stress induced a significant increase in heart rate which was not observed in DHA-fed group. The time evolution of the systolic blood pressure was not affected by the stress and was roughly similar in the stressed rats of either dietary group. Conversely, the systolic blood pressure decreased in the unstressed rats fed DHA. Similar data were obtained for the diastolic blood pressure. The beneficial effect of DHA was also observed on cardiac contractility, since the dP/dt(max) increase was prevented in the DHA-fed rats. The stress-induced modifications were associated with an increase in cardiac noradrenaline level which was not observed in DHA-fed rats. The fatty acid composition of adrenals was significantly related to the fatty acid intake particularly the
Weber, Heinz S; Selimi, Dzevair; Huber, Gustav
30 years ago the observation of a lower incidence of cardiovascular diseases in Inuits (Eskimos) was related to the higher fish consumption when compared to the residual Danish population. Clinical studies confirmed this finding. It was explained by the higher content of polyunsaturated fatty acids (PUFA) in fish, especially of omega-3 PUFAs. Experimental studies in cell cultures and also in animals with and without infarction models verified the anti-arrhythmic effect of omega-3 PUFAs among other possible contributing factors when compared to other fatty acids. In clinical studies a significant reduction (ca. 40%) of sudden cardiac deaths (SCD) could be found in patients after an acute myocardial infarction, if they were treated with at least 1 g omega-3 PUFAs daily, either by consumption of fish twice weekly or of a highly purified preparation omega-3 PUFAs in capsules. These findings led to recommendations of the American Heart Association and the European Society of Cardiology to a higher fish consumption and/or the daily intake of 1 g omega-3 PUFAs for primary and especially for secondary prevention of cardiovascular diseases. The much fewer side-effects, and the standardised dosage on one hand and the negative effect of the sometimes higher mercury content of fish make the intake of omega-3 PUFAs as capsules the better choice.
Wang, Xiumei; Li, Daoming; Qu, Man; Durrani, Rabia; Yang, Bo; Wang, Yonghua
Immobilization of lipase MAS1 from marine Streptomyces sp. strain W007 and its application in catalyzing esterification of n-3 polyunsaturated fatty acids (PUFA) with glycerol were investigated. The resin XAD1180 was selected as a suitable support for the immobilization of lipase MAS1, and its absorption ability was 75mg/g (lipase/resin ratio) with initial buffer pH value of 8.0. The thermal stability of immobilized MAS1 was improved significantly compared with that of the free lipase. Immobilized MAS1 had no regiospecificity in the hydrolysis of triolein. The highest esterification degree (99.31%) and TAG content (92.26%) by immobilized MAS1-catalyzed esterification were achieved under the optimized conditions, which were significantly better than those (82.16% and 47.26%, respectively) by Novozym 435. More than 92% n-3 PUFA was incorporated into TAG that had similar fatty acids composition to the substrate (n-3 PUFA). The immobilized MAS1 exhibited 50% of its initial activity after being used for five cycles.
Scarsi, Claudia; Levesque, Ann; Lisi, Lucia; Navarra, Pierluigi
The high complexity of n-3 fatty acids absorption process, along with the huge amount of endogenous fraction, makes bioavailability studies with these agents very challenging and deserving special consideration. In this paper we report the results of a bioequivalence study between a new formulation of EPA+DHA ethyl esters developed by IBSA Institut Biochimique and reference medicinal product present on the Italian market. Bioequivalence was demonstrated according to the criteria established by the EMA Guideline on the Investigation of Bioequivalence. We found that the free fractions represent a better and more sensitive end-point for bioequivalence investigations on n-3 fatty acids, since: (i) the overall and intra-subject variability of PK parameters was markedly lower compared to the same variability calculated on the total DHA and EPA fractions; (ii) the absorption process was completed within 4h, and the whole PK profile could be drawn within 12-15 h from drug administration.
Bae, Jin-Sik; Park, Jong-Min; Lee, Junghoon; Oh, Byung-Chul; Jang, Sang-Ho; Lee, Yun Bin; Han, Young-Min; Ock, Chan-Young; Cha, Ji-Young; Hahm, Ki-Baik
Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk for progression to hepatocellular carcinoma in addition to comorbidities such as cardiovascular and serious metabolic diseases; however, the current therapeutic options are limited. Based on our previous report that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can significantly ameliorate high fat diet (HFD)-induced NAFLD, we explored the therapeutic efficacy of n-3 PUFAs and N-IgY, which is a chicken egg yolk-derived IgY specific for the Niemann-Pick C1-Like 1 (NPC1L1) cholesterol transporter, on NAFLD in mice. We generated N-IgY and confirmed its efficient cholesterol transport-blocking activity in HepG2 and Caco-2 cells, which was comparable to the effect of ezetimibe (EZM). C57BL/6 wild type and fat-1 transgenic mice, capable of producing n-3 PUFAs, were fed a high fat diet (HFD) alone or supplemented with N-IgY. Endogenously synthesized n-3 PUFAs combined with N-IgY led to significant decreases in hepatic steatosis, fibrosis, and inflammation (p<0.01). The combination of N-IgY and n-3 PUFAs resulted in significant upregulation of genes involved in cholesterol uptake (LDLR), reverse cholesterol transport (ABCG5/ABCG8), and bile acid metabolism (CYP7A1). Moreover, fat-1 transgenic mice treated with N-IgY showed significant downregulation of genes involved in cholesterol-induced hepatic stellate cell activation (Tgfb1, Tlr4, Col1a1, Col1a2, and Timp2). Collectively, these data suggest that n-3 PUFAs and N-IgY, alone or in combination, represent a promising treatment strategy to prevent HFD-induced fatty liver through the activation cholesterol catabolism to bile acids and by decreasing cholesterol-induced fibrosis.
Heinze, Verónica M; Actis, Adriana B
The role of dietary fatty acids on cancer is still controversial. To examine the current literature on the protective role of conjugated linoleic acid (CLA) and marine long-chain fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and the risk of breast and prostate cancer, data from 41 case-control and cohort studies and relevant in vitro and animal experiments were included in this 2000-2010 revision. Epidemiological studies on CLA intake or its tissue concentration related to breast and prostate tumorigenesis are not conclusive; EPA and DHA intake have shown important inverse associations just in some studies. Additional research on the analysed association is required.
Assisi, Alessandro; Banzi, Rita; Buonocore, Carmela; Capasso, Filippo; Di Muzio, Valeria; Michelacci, Francesca; Renzo, Danila; Tafuri, Giovanni; Trotta, Francesco; Vitocolonna, Maria; Garattini, Silvio
Epidemiological and experimental studies have indicated that consumption of more n-3 long-chain polyunsaturated fatty acids may reduce the risk for a variety of diseases, including cardiovascular, neurological and immunological disorders, diabetes and cancer. This article focuses on the role of marine n-3 long-chain polyunsaturated fatty acids in brain functions, including the development of the central nervous system and neurological disorders. An overview of the major animal studies and clinical trials is provided here, focusing on fatty acid supplementation during pregnancy and infancy, and prevention and management of Alzheimer's disease, schizophrenia, depression and attention deficit hyperactive disorder. Although an optimal balance in n-3/n-6 long-chain polyunsaturated fatty acid ratio is important for proper neurodevelopment and cognitive functions, results from randomized controlled trials are controversial and do not confirm any useful effect of supplementation on development of preterm and term infants. The relationship between fatty acid status and mental disorders is confirmed by reduced levels of n-3 long-chain polyunsaturated fatty acids in erythrocyte membranes of patients with central nervous system disorders. Nevertheless, there are very little data supporting the use of fish oil in those patients. The only way to verify whether n-3 long-chain polyunsaturated fatty acids are a potential therapeutic option in the management and prevention of mental disorders is to conduct a large definitive randomized controlled trials similar to those required for the licensing of any new pharmacological treatment.
Chia (Salvia hispanica L.) seed as an n-3 fatty acid source for finishing pigs: effects on fatty acid composition and fat stability of the meat and internal fat, growth performance, and meat sensory characteristics.
Coates, W; Ayerza, R
Coronary heart disease is caused by arteriosclerosis, which is triggered by an unbalanced fatty acid profile in the body. Today, Western diets are typically low in n-3 fatty acids and high in SFA and n-6 fatty acids; consequently, healthier foods are needed. Chia seed (Salvia hispanica L.), which contains the greatest known plant source of n-3 alpha-linolenic acid, was fed at the rate of 10 and 20% to finishing pigs, with the goal to determine if this new crop would increase the n-3 content of the meat as has been reported for other n-3 fatty acid-rich crops. The effects of chia on fatty acid composition of the meat, internal fats, growth performance, and meat sensory characteristics were determined. Productive performance was unaffected by dietary treatment. Chia seed modified the fatty acid composition of the meat fat, but not of the internal fat. Significantly (P < 0.05) less palmitic, stearic, and arachidic acids were found with both chia treatments. This is different than trials in which flaxseed, another plant based source of omega-3 fatty acid, has been fed. Alpha-linolenic acid content increased with increasing chia content of the diet; however, only the effect of the 20% ration was significantly (P < 0.05) different from that of the control. Chia seed increased panel member preferences for aroma and flavor of the meat. This study tends to show that chia seems to be a viable feed that can produce healthier pork for human consumption.
Appleton, K M; Grippo, A J; Beltz, T G; Johnson, A K
n-3 Polyunsaturated fatty acids (n-3PUFAs) may be beneficial for anxiety and depression under stressful conditions. Studies however, typically utilise physical or sudden physiological stress, while gradual physiological stress is also relevant to human conditions. Using deoxycorticosterone acetate (DOCA) administration to induce gradual physiological stress, this study investigated the impact of n-3PUFAs under gradual physiological stress in rats. Animals (aged 2 months) (N=8-12/group) received daily injections of DOCA or vehicle and were concurrently fed a high n-3PUFA or control diet for eight weeks. Behavioural measures were taken throughout. Behavioural tests and physiological measures were conducted after six and eight weeks respectively. DOCA administration decreased plasma renin, plasma proteins and relative adrenal weight, and increased water intake, relative kidney weight, and anxiety in the open field. These findings demonstrate disruptions to the renin-angiotensin-aldosterone system, a result of mild physiological stress, that also impact on anxiety behaviours. No effects of n-3PUFAs were found.
Huang, Wei; Wang, Bin; Li, Xiangyong; Kang, Jing X
Effective means for the prevention of alcohol-induced liver disease, a global health problem, have yet to be developed. We evaluated whether the high endogenous levels of omega-3 polyunsaturated acids (n-3 PUFA) in fat-1 transgenic mice could protect them against acute ethanol-induced liver steatosis. We induced alcoholic liver steatosis in 9-week-old male heterozygous fat-1 mice and their wild-type (WT) male littermates through three oral gavages of 60% ethanol at 4.7 g/kg body weight. Hepatic lipid accumulation was significantly increased in both alcohol treatment groups, but by much less in the fat-1 group compared with the WT group. Fat-1 mice exhibited significantly lower levels of total hepatic/plasma TG and plasma alanine aminotransferase activity. Accordingly, hepatic expression of lipogenesis-related genes (e.g., SREBP-1c, FAS, and SCD-1) and plasma levels of inflammatory cytokines (e.g., IL-6, TNF-α, and MCP-1) were reduced in the fat-1 mice. Furthermore, decreased hepatic expression of cytochrome P450 2E1 (CYP2E1) and increased hepatic levels of PPAR-α and HO-1 were observed in the fat-1 mice, compared to the WT mice. These findings show that elevated tissue n-3 PUFA protect against acute ethanol-induced liver steatosis in fat-1 mice, possibly through the down-regulation of hepatic lipogenesis, inflammatory response, and oxidative stress.
This experiment was conducted to investigate the effects of dietary ratios of n-6:n-3 polyunsaturated fatty acids (PUFA) on the performance of lactating sows and their piglets. Thirty pregnant Landrace sows were assigned to one of three treatments from d 108 of gestation until weaning (26–29 d) and were fed diets containing different ratios of n-6:n-3 PUFA including 3:1, 9:1 and 13:1. The effects on sow and litter production traits were examined together with an assessment of sow body condition. No differences were detected among the treatments for the daily feed intake of sows or changes in sow weight and back-fat levels during lactation (P > 0.05). Litter size at d 14 and d 21 were tended to increase in 3:1 treatment compared with 9:1 and 13:1 treatments (P < 0.10). Litter weight gain (1.77 kg/d) from d 0 to d 14 was tended to increase in 9:1 groups compared with the other two treatments (P < 0.10). A significant difference was observed for the content of α -linolenic acid, total n-3 PUFA, and the ratio of n-6:n-3 PUFA in the colostrum, milk, and piglets plasma (P < 0.01). The effects of different ratios of n-6:n-3 PUFA in sow diets on colostrum, milk, and piglet plasma immunoglobulin concentrations are studied. No difference was observed among treatments in the concentrations of IgM, and IgA in colostrum (P > 0.05). A great significant difference for IgG concentration was observed among 3 group in colostrum. A great significant difference for IgA, and IgM (P < 0.01) concentrations in piglet plasma at d14 and a significant difference for IgG(P < 0.05) was observed at d14. Furthermore, at d 21 of lactation, piglet plasma IgG and IgA concentration were greater in 3:1 compared with 13:1 group (P < 0.01). In summary, the current study demonstrated that altering the ratio of n-6:n-3 PUFA in lactating sow diet had an effect on the immune component including immunoglobulin and cytokines, and it tended to increase the litter average
Yao, Wei; Li, Jie; Wang, Jun Jun; Zhou, Weiliang; Wang, Qingbo; Zhu, Rongchang; Wang, Fenglai; Thacker, Phil
This experiment was conducted to investigate the effects of dietary ratios of n-6:n-3 polyunsaturated fatty acids (PUFA) on the performance of lactating sows and their piglets. Thirty pregnant Landrace sows were assigned to one of three treatments from d 108 of gestation until weaning (26-29 d) and were fed diets containing different ratios of n-6:n-3 PUFA including 3:1, 9:1 and 13:1. The effects on sow and litter production traits were examined together with an assessment of sow body condition. No differences were detected among the treatments for the daily feed intake of sows or changes in sow weight and back-fat levels during lactation (P > 0.05). Litter size at d 14 and d 21 were tended to increase in 3:1 treatment compared with 9:1 and 13:1 treatments (P < 0.10). Litter weight gain (1.77 kg/d) from d 0 to d 14 was tended to increase in 9:1 groups compared with the other two treatments (P < 0.10). A significant difference was observed for the content of α -linolenic acid, total n-3 PUFA, and the ratio of n-6:n-3 PUFA in the colostrum, milk, and piglets plasma (P < 0.01). The effects of different ratios of n-6:n-3 PUFA in sow diets on colostrum, milk, and piglet plasma immunoglobulin concentrations are studied. No difference was observed among treatments in the concentrations of IgM, and IgA in colostrum (P > 0.05). A great significant difference for IgG concentration was observed among 3 group in colostrum. A great significant difference for IgA, and IgM (P < 0.01) concentrations in piglet plasma at d14 and a significant difference for IgG(P < 0.05) was observed at d14. Furthermore, at d 21 of lactation, piglet plasma IgG and IgA concentration were greater in 3:1 compared with 13:1 group (P < 0.01).In summary, the current study demonstrated that altering the ratio of n-6:n-3 PUFA in lactating sow diet had an effect on the immune component including immunoglobulin and cytokines, and it tended to increase the litter average
Christensen, J H; Aarøe, J; Knudsen, N; Dideriksen, K; Kornerup, H J; Dyerberg, J; Schmidt, E B
Patients with chronic renal failure (CRF) often have autonomic cardiac dysfunction, which can be assessed by measuring heart rate variability (HRV). This dysfunction prediposes the patients to sudden cardiac death. This study describes 24-hour HRV in patients with CRF compared to HRV in patients with a previous myocardial infarction (MI). Furthermore, associations between HRV in patients with CRF and the content of n-3 polyunsaturated fatty acids (PUFA) in cell membranes were examined, because n-3 PUFA may improve HRV. Twenty-nine patients with CRF treated with dialysis were enrolled. A 24-hour Holter recording was obtained at baseline and the HRV variables, RR (= mean of all normal RR intervals during the 24-hour recording) and SDNN (= standard deviation of all normal RR intervals in the entire 24-hour recording) were analyzed. Also, granulocyte fatty acid composition was determined. The patients were allocated to dietary supplementation with either 5.2 g of n-3 PUFA or a placebo oil (olive oil) daily for 12 weeks in a double-blind design. At the end of the supplementation period the Holter recording and blood sampling were repeated. At baseline the CRF patients' mean SDNN ws 86 ms compared to 118 ms (p < 0.01) in patients with a previous MI. After supplementation with either n-3 PUFA or placebo a highly significant correlation was observed between the content of n-3 PUFA in cell membranes and HRV (r = 0.71, p < 0.01). Furthermore, when the patients were dichotomized according to their mean SDNN, it was found, that those with the highest SDNN had a higher content of n-3 PUFA in cell membranes compared to those with the lowest SDNN (7.8% vs 4.2%, p < 0.05). In conclusion, HRV was decreased in CRF patients indicating a cardiovascular autonomic dysfunction. The positive correlation between the n-3 PUFA content in cell membranes and HRV suggests that the effects of an increased intake of n-3 PUFA in CRF patients should be further studied.
Beydoun, May A; Fanelli Kuczmarski, Marie T; Beydoun, Hind A; Rostant, Ola S; Evans, Michele K; Zonderman, Alan B
In the present study, we examined longitudinal changes in self-reported depressive symptoms (and related domains) in relation to baseline intakes of n-3 fatty acids (absolute and relative to n-6 fatty acids). Sex-specific associations were evaluated in a prospective cohort of adults (n = 2,053) from Baltimore, Maryland, who were 30-64 years of age at baseline and were followed for a mean of 4.65 (standard deviation, 0.93) years (2004-2013). Using mean intakes of n-3 and n-6 fatty acids reported on two 24-hour dietary recalls, we estimated the ratios of n-3 to n-6 fatty acids for both highly unsaturated fatty acids (≥20 carbon atoms) (HUFAs) and polyunsaturated fatty acids (≥18 carbon atoms) (PUFAs). Outcomes included total and domain-specific scores on the 20-item Center for Epidemiologic Studies-Depression scale. Based on mixed-effects regression models, among women, both higher n-3 HUFA:n-6 PUFA and n-3 PUFA:n-6 PUFA ratios were associated with a slower rate of increase in total Center for Epidemiologic Studies-Depression scores over time. Higher n-3 HUFA:n-6 HUFA ratios were associated with slower increases in somatic complaints in men, whereas among women, higher n-3 HUFA:n-6 PUFA and n-3 PUFA:n-6 PUFA ratios were both linked to putative longitudinal improvement in positive affect over time. Among US adults, n-3:n-6 dietary fatty acid ratio was associated with longitudinal changes in depressive symptoms, with a higher ratio linked to a slower increase in depressive symptoms over time, particularly among women.
Salen, Patricia; Gaci, Nadia; Tottey, William; Calani, Luca; Bresciani, Letizia; López-Gutiérrez, Noelia; Hazane-Puch, Florence; Laporte, François; Brugère, Jean-François; Del Rio, Daniele; Demeilliers, Christine; de Lorgeril, Michel
Background Whole rye (WR) consumption seems to be associated with beneficial health effects. Although rye fiber and polyphenols are thought to be bioactive, the mechanisms behind the health effects of WR have yet to be fully identified. This study in rats was designed to investigate whether WR can influence the metabolism of n-3 and n-6 long-chain fatty acids (LCFA) and gut microbiota composition. Methods For 12 weeks, rats were fed a diet containing either 50% WR or 50% refined rye (RR). The WR diet provided more fiber (+21%) and polyphenols (+29%) than the RR diet. Fat intake was the same in both diets and particularly involved similar amounts of essential (18-carbon) n-3 and n-6 LCFAs. Results The WR diet significantly increased the 24-hour urinary excretion of polyphenol metabolites–including enterolactone–compared with the RR diet. The WR rats had significantly more n-3 LCFA–in particular, eicosapentanoic (EPA) and docosahexanoic (DHA) acids–in their plasma and liver. Compared with the RR diet, the WR diet brought significant changes in gut microbiota composition, with increased diversity in the feces (Shannon and Simpson indices), decreased Firmicutes/Bacteroidetes ratio and decreased proportions of uncultured Clostridiales cluster IA and Clostridium cluster IV in the feces. In contrast, no difference was found between groups with regards to cecum microbiota. The WR rats had lower concentrations of total short-chain fatty acids (SCFA) in cecum and feces (p<0.05). Finally, acetate was lower (p<0.001) in the cecum of WR rats while butyrate was lower (p<0.05) in the feces of WR rats. Interpretation This study shows for the first time that WR consumption results in major biological modifications–increased plasma and liver n-3 EPA and DHA levels and improved gut microbiota profile, notably with increased diversity–known to provide health benefits. Unexpectedly, WR decreased SCFA levels in both cecum and feces. More studies are needed to understand the
Our study determined if flaxseed treated with a formaldehyde-free process increased n-3 fatty acid (FA) levels in ruminant muscle. Twenty-four lambs (initial BW 43.8 ± 4.4 kg) were randomly divided into 4 groups for a 90-d trial. One treatment group (FLX) was fed 136 g/d of non-treated ground flaxse...
Recent studies suggest that feeding long-chain n-3 fatty acids (LCn-3FA) in the diet may blunt the developmental reduction in insulin sensitivity and anabolism in the neonate piglet. To examine the effect of LCn-3FA on protein anabolism, 2-day-old piglets (n=28) were weaned and assigned to one of t...
Galmiche, Guillaume; Huneau, Jean-François; Mathé, Véronique; Mourot, Jacques; Simon, Noémie; Le Guillou, Céline; Hermier, Dominique
In obese subjects, the loss of fat mass during energy restriction is often accompanied by a loss of muscle mass. The hypothesis that n-3 PUFA, which modulate protein homoeostasis via effects on insulin sensitivity, could contribute to maintain muscle mass during energy restriction was tested in rats fed a high-fat diet (4 weeks) rich in 18 : 1 n-9 (oleic acid, OLE-R), 18 : 3 n-3 (α-linolenic acid, ALA-R) or n-3 long-chain (LC-R) fatty acid and then energy restricted (8 weeks). A control group (OLE-ad libitum (AL)) was maintained with AL diet throughout the study. Rats were killed 10 min after an i.v. insulin injection. All energy-restricted rats lost weight and fat mass, but only the OLE-R group showed a significant muscle loss. The Gastrocnemius muscle was enriched with ALA in the ALA-R group and with LC-PUFA in the ALA-R and LC-R groups. The proteolytic ubiquitin-proteasome system was differentially affected by energy restriction, with MAFbx and muscle ring finger-1 mRNA levels being decreased in the LC-R group (-30 and -20 %, respectively). RAC-α serine/threonine-protein kinase and insulin receptor substrate 1 phosphorylation levels increased in the LC-R group (+70 %), together with insulin receptor mRNA (+50 %). The ALA-R group showed the same overall activation pattern as the LC-R group, although to a lesser extent. In conclusion, dietary n-3 PUFA prevent the loss of muscle mass associated with energy restriction, probably by an improvement in the insulin-signalling pathway activation, in relation to enrichment of plasma membranes in n-3 LC-PUFA.
Background Adequate biomarkers for the dietary supply of fatty acids (FA) are FA of adipose tissue and blood fractions. In human studies, invasive sample collection is unpleasant for subjects. In contrast, cheek cell sampling can be considered as a non-invasive alternative to investigate FA status. The aim of this study was to analyze whether cheek cell FA composition reflect the supplementation of alpha-linolenic acid (ALA) using a linseed oil mixture compared to olive oil supplementation. Additionally, it was investigated if cheek cell FA composition correlates with the FA composition of plasma, red blood cells (RBC) and peripheral blood mononuclear cells (PBMC) before and during both interventions. Methods During a 10-week randomized, controlled, double-blind human intervention study, 38 subjects provided cheek cell and blood samples. After a two-week run-in period, the test group (n = 23) received 17 g/d of an ALA-rich linseed oil mixture, while the control group (n = 15) received 17 g/d of an omega-3 (n-3) polyunsaturated FA (PUFA)-free olive oil. Cheek cells and blood were collected on days 0, 7 and 56 of the 8-week intervention period. Results Compared to olive oil, the linseed oil intervention increased ALA and also the endogenously converted long-chain n-3 metabolites eicosatetraenoic-, eicosapentaenoic- and docosapentaenoic acid in cheek cells (P ≤ 0.05). Docosahexaenoic acid remained unchanged. Reflecting the treatment, the n-6/n-3 ratio decreased in the test group. In general, cheek cell FA reflected the changes of FA in blood fractions. Independent of treatment, significant correlations (P ≤ 0.05) of n-6 PUFA and n-3 PUFA between cheek cells and plasma, RBC and PBMC were found, except for linoleic acid and ALA. Conclusions The changes in FA composition of cheek cells confirmed that ALA from linseed oil increased endogenously derived n-3 PUFA in cheek cell lipids. These changes in cheek cells and their correlation to the respective
Hiratsuka, Seiichi; Honma, Hiroyuki; Saitoh, Yoichi; Yasuda, Yuki; Yokogoshi, Hidehiko
The effects of dietary sialic acid in dams on the learning abilities of their pups after weaning were investigated using rats deficient in n-3 fatty acids. Nine-week-old female Wistar rats were fed an n-3 fatty acid-deficient diet for 3 wk and were mated at 12 wk of age. During pregnancy and lactation, the female rats were fed the n-3 fatty acid-deficient diet, and were given water or water containing 1% N-acetylneuraminic acid (NANA) ad libitum. After weaning, the learning abilities of the pups were evaluated using a novel object recognition test. The recognition index of pups nursed by dams fed on water containing 1% NANA (NANA-intake dams) was significantly higher than that of pups nursed by dams fed only on water (NANA non-intake dams). There were no significant differences in the total sialic acid or docosahexaenoic acid contents in the cerebral cortex or hippocampus of pups nursed by dams fed on either type of water. The total dimethylacetal (DMA, from plasmalogen) level in the cerebral cortex of pups nursed by NANA-intake dams was significantly higher than that of pups nursed by NANA non-intake dams. These results suggest that dietary sialic acid in dams during pregnancy and lactation might be beneficial for the learning abilities of pups after weaning, which may be related to the plasmalogen level in the brain of pups.
Soulimane-Mokhtari, Nassima A; Guermouche, Baya; Yessoufou, Akadiri; Saker, Myrieum; Moutairou, Kebirou; Hichami, Aziz; Merzouk, Hafida; Khan, Naim A
The time course of changes in lipid metabolism by dietary n-3 PUFAs (polyunsaturated fatty acids) in streptozotocin-induced diabetic rats during pregnancy (days 12 and 21) and their macrosomic offspring at birth (day 0) and through adulthood (days 60 and 90) was studied with respect to adipose tissue, liver and serum lipid concentrations, and fatty acid composition. Glucose and insulin levels were also assessed in order to characterize the diabetic state of macrosomic offspring. Pregnant diabetic and control rats were fed either an Isio-4 or EPAX diet (enriched with n-3 PUFA). The same diets were also consumed by pups at weaning. Compared with control rats, during pregnancy diabetic rats had a significant elevation in liver and serum triacylglycerol (triglyceride) and cholesterol concentrations. At birth, macrosomic pups had higher serum insulin and glucose levels than control pups. The macrosomic rats maintained accelerated postnatal growth combined with high adipose tissue weight and lipid content through the first 12 weeks of age. The macrosomic pups from diabetic rats fed the Isio-4 diet also showed a significant enhancement in liver and serum triacylglycerol and cholesterol levels at birth and during adulthood. Feeding the EPAX diet to diabetic mothers as well as their macrosomic pups increased serum and liver levels of EPA (eicospentaenoic acid) and DHA (docosahexaenoic acid) with a reduction in arachidonic acid. The EPAX diet induced a significant decrease in liver and serum triacylglycerol and cholesterol concentrations in mothers during pregnancy and in their macrosomic pups during adulthood. Since the EPAX diet improves lipid anomalies considerably in diabetic mothers and their macrosomic offspring, it may prevent long-term metabolic abnormalities associated with macrosomia.
Baba, Yasmina; Kallas, Zein; Costa-Font, Montserrat; Gil, José María; Realini, Carolina E
The impact of hedonic evaluation on consumers' preferences for beef attributes was evaluated (origin, animal diet, fat content, color, price) including its enrichment with omega-3 (n-3) and conjugated linoleic acid (CLA) fatty acids. One group of consumers (n=325) received information about n-3 and CLA, while the other group (n=322) received no information. Consumers conducted a Discrete Choice Experiment (DCE), using the recently developed Generalized Multinomial Logit model; followed by a blind hedonic evaluation of beef samples, which were identified after tasting, and finally repeated the DCE. Results showed that hedonic evaluation had a significant impact on consumers' preferences, which were similar after tasting for all consumers, with less emphasis on the fat content, color, and origin attributes and greater emphasis on animal diet. Preference for n-3 enriched beef increased, while preference for CLA enriched beef was still not significant after tasting. The information provided had a significant effect on consumers' beef preferences, but no significant impact on beef liking scores.
Crispie, Fiona; O’Sullivan, Orla; Cotter, Paul; Stanton, Catherine; Kelly, Philip; Cryan, John F.; Dinan, Timothy G.
Background Early life stress is a risk factor for many psychiatric disorders ranging from depression to anxiety. Stress, especially during early life, can induce dysbiosis in the gut microbiota, the key modulators of the bidirectional signalling pathways in the gut-brain axis that underline several neurodevelopmental and psychiatric disorders. Despite their critical role in the development and function of the central nervous system, the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the regulation of gut-microbiota in early-life stress has not been explored. Methods and Results Here, we show that long-term supplementation of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (80% EPA, 20% DHA) n-3 PUFAs mixture could restore the disturbed gut-microbiota composition of maternally separated (MS) female rats. Sprague-Dawley female rats were subjected to an early-life stress, maternal separation procedure from postnatal days 2 to 12. Non-separated (NS) and MS rats were administered saline, EPA/DHA 0.4 g/kg/day or EPA/DHA 1 g/kg/day, respectively. Analysis of the gut microbiota in adult rats revealed that EPA/DHA changes composition in the MS, and to a lesser extent the NS rats, and was associated with attenuation of the corticosterone response to acute stress. Conclusions In conclusion, EPA/DHA intervention alters the gut microbiota composition of both neurodevelopmentally normal and early-life stressed animals. This study offers insights into the interaction between n-3 PUFAs and gut microbes, which may play an important role in advancing our understanding of disorders of mood and cognitive functioning, such as anxiety and depression. PMID:26426902
Conklin, Sarah M; Runyan, Caroline A; Leonard, Sherry; Reddy, Ravinder D; Muldoon, Matthew F; Yao, Jeffrey K
Accumulating evidence finds a relative deficiency of peripheral membrane fatty acids in persons with affective disorders such as unipolar and bipolar depression. Here we sought to investigate whether postmortem brain fatty acids within the anterior cingulate cortex (BA-24) varied according to the presence of major depression at the time of death. Using capillary gas chromatography we measured fatty acids in a depressed group (n=12), and in a control group without lifetime history of psychiatric diagnosis (n=14). Compared to the control group, the depressed group showed significantly lower concentrations of numerous saturated and polyunsaturated fatty acids including both the n-3 and n-6 fatty acids. Additionally, significant correlations between age at death and precursor (or metabolites) in the n-3 fatty acid pathway were demonstrated in the depressed group but not in control subjects. In the n-6 fatty acid family, the ratio of 20:3(n-6)/18:2(n-6) was higher in patients than in control groups, whereas the ratio of 20:4(n-6)/20:3(n-6) was relatively decreased in patients. Lastly, a significant negative correlation between age and the ratio of 20:4(n-6) to 22:6(n-3) was found in patients, but not in controls. Taken together, decreases in 22:6(n-3) may be caused, at least in part, by the diminished formation of 20:5(n-3), which is derived from 20:4(n-3) through a Delta5 desaturase reaction. The present findings from postmortem brain tissue raise the possibility that an increased ratio of 20:4(n-6) to 22:6(n-3) may provide us with a biomarker for depression. Future research should further investigate these relationships.
Moallem, U; Zachut, M
The passage of long-chain fatty acids (FA) through the placenta in ruminants is limited. However, essential long-chain polyunsaturated FA, and especially n-3 FA, are crucial for normal development of the bovine fetus; therefore, uptake of these FA by the embryo must occur during pregnancy. The objectives of the present study were to examine the effects of enrichment of dam plasma with various n-3 FA during late gestation on newborn calf plasma FA composition. Twenty-seven multiparous cows at 256 d of pregnancy were divided into 3 groups and fed encapsulated fats as follows: 1) control: supplemented at 240 g/d per cow with saturated FA; 2) flaxseed oil (FLX): supplemented at 300 g/d per cow with fat that provided 56.1g/d per cow of α-linolenic acid (ALA) from flaxseed oil; and 3) fish oil (FO): supplemented at 300 g/d per cow with fat that provided 5.8 and 4.3g/d per cow eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil, respectively. Blood samples were taken from dams twice weekly and from calves immediately after calving before first colostrum. The FA composition in plasma was determined in dams at the last sample before parturition, on average 2d before calving. Feeding cows with FLX resulted in a 2.6-fold increase in the proportion of ALA in dam plasma as compared with the control. The proportion of EPA in cow plasma was not different between groups; however, the percentage of docosapentaenoic acid (DPA) was 1.4 and 2 times higher, respectively, in cows fed FLX and FO than in the controls. In addition, the plasma proportion of DHA was 15 times higher in FO cows than in controls. In calves, no differences between groups were observed in the plasma proportions of ALA and EPA; however, the proportion of DHA was 1.9 times higher in the FO calves than in controls. Across treatments, data showed no correlation between the proportions of ALA, EPA, and DPA in dam and calf plasma; however, positive correlation was demonstrated between dams and
Lapis, Trina J; Oliveira, Alexandra C M; Crapo, Charles A; Himelbloom, Brian; Bechtel, Peter J; Long, Kristy A
Establishing n-3 polyunsaturated fatty acid contents in canned wild Alaska pink salmon products is challenging due to ample natural variation found in lipid content of pink salmon muscle. This study investigated the effect of adding salmon oil (SO) to canned pink salmon produced from fish exhibiting two opposite degrees of skin watermarking, bright (B) and dark (D). Specific goals of the study were to evaluate the benefits of adding SO to canned pink salmon with regard to nutritional value of the product, sensory characteristics, and the oxidative and hydrolytic stability of the lipids over thermal processing. Six groups of canned pink salmon were produced with variable levels of SO, either using bright (with 0, 1, or 2% SO) or dark (with 0, 2, or 4% SO) pink salmon. Compositional analysis revealed highest (P < 0.05) lipid content in sample B2 (8.7%) and lowest (P < 0.05) lipid content in sample D0 (3.5%). Lipid content of samples B0, B1, D2, and D4 was not significantly different (P > 0.05) ranging from 5.7% to 6.8%. Consequently, addition of SO to canned pink salmon allowed for consistent lipid content between bright and dark fish. Addition of 1% or 2% SO to canned bright pink salmon was not detrimental to the sensory properties of the product. It is recommended that canned bright pink salmon be supplemented with at least 1% SO, while supplementation with 2% SO would guarantee a minimum quantity of 1.9 g of n-3 fatty acids per 100 g of product. Addition of 4% SO to canned dark pink salmon was detrimental to product texture and taste, while supplementation with 2% SO did not negatively affect sensorial properties of the product. Accordingly, canned dark pink salmon should be supplemented with 2% SO so that a minimum n-3 fatty acids content of 1.5 g per 100 g of product.
Ticinesi, Andrea; Meschi, Tiziana; Lauretani, Fulvio; Felis, Giovanna; Franchi, Fabrizio; Pedrolli, Carlo; Barichella, Michela; Benati, Giuseppe; Di Nuzzo, Sergio; Ceda, Gian Paolo; Maggio, Marcello
Chronic activation of the inflammatory response, defined as inflammaging, is the key physio-pathological substrate for anabolic resistance, sarcopenia and frailty in older individuals. Nutrients can theoretically modulate this phenomenon. The underlying molecular mechanisms reducing the synthesis of pro-inflammatory mediators have been elucidated, particularly for vitamin D, n-3 polyunsaturated fatty acids (PUFA) and whey proteins. In this paper, we review the current evidence emerging from observational and intervention studies, performed in older individuals, either community-dwelling or hospitalized with acute disease, and evaluating the effects of intake of vitamin D, n-3 PUFA and whey proteins on inflammatory markers, such as C-Reactive Protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). After the analysis, we conclude that there is sufficient evidence for an anti-inflammatory effect in aging only for n-3 PUFA intake, while the few existing intervention studies do not support a similar activity for vitamin D and whey supplements. There is need in the future of large, high-quality studies testing the effects of combined dietary interventions including the above mentioned nutrients on inflammation and health-related outcomes. PMID:27043616
Ticinesi, Andrea; Meschi, Tiziana; Lauretani, Fulvio; Felis, Giovanna; Franchi, Fabrizio; Pedrolli, Carlo; Barichella, Michela; Benati, Giuseppe; Di Nuzzo, Sergio; Ceda, Gian Paolo; Maggio, Marcello
Chronic activation of the inflammatory response, defined as inflammaging, is the key physio-pathological substrate for anabolic resistance, sarcopenia and frailty in older individuals. Nutrients can theoretically modulate this phenomenon. The underlying molecular mechanisms reducing the synthesis of pro-inflammatory mediators have been elucidated, particularly for vitamin D, n-3 polyunsaturated fatty acids (PUFA) and whey proteins. In this paper, we review the current evidence emerging from observational and intervention studies, performed in older individuals, either community-dwelling or hospitalized with acute disease, and evaluating the effects of intake of vitamin D, n-3 PUFA and whey proteins on inflammatory markers, such as C-Reactive Protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). After the analysis, we conclude that there is sufficient evidence for an anti-inflammatory effect in aging only for n-3 PUFA intake, while the few existing intervention studies do not support a similar activity for vitamin D and whey supplements. There is need in the future of large, high-quality studies testing the effects of combined dietary interventions including the above mentioned nutrients on inflammation and health-related outcomes.
Davidson, B C; Girao, L A F; Giangregorio, A
There is now considerable evidence that polyunsaturated fatty acids (PUFA) are effective in vitro at limiting the growth of cancer cells while not affecting normal cells to the same extent. Twenty carbon PUFA, especially of the n3 series, have been shown to be particularly potent; while the eighteen carbon n6 fatty acid, linoleic acid has been implicated in growth stimulation of breast cancer. We report here on the comparative effects of a range of eighteen and twenty carbon fatty acids of varying degrees of unsaturation on normal and transformed fibroblasts in culture. All moieties of the n3 series showed high potency in limiting transformed cell growth, while cis and trans monounsaturates and pre-delta-6-desaturation n6 polyunsaturates induced a mixed response, even inducing comparative growth stimulation with some fatty acid concentrations.
Ethanol withdrawal is a potentially life-threatening neurological syndrome owing to decreased GABA transmission and increased glutamatergic transmission resulting in a pro-excitotoxic state. Previous data indicate that ethanol withdrawal may increase CNS lipid peroxidation particularly to the n-3 fa...
Ji, Shaonin; Hardy, Robert W; Wood, Philip A
The fat-1 gene, derived from Caenorhabditis elegans, encodes for a fatty acid n-3 desaturase. In order to study the potential metabolic benefits of n-3 fatty acids, independent of dietary fatty acids, we developed seven lines of fat-1 transgenic mice (C57/BL6) controlled by the regulatory sequences of the adipocyte protein-2 (aP2) gene for adipocyte-specific expression (AP-lines). We were unable to obtain homozygous fat-1 transgenic offspring from the two highest expressing lines, suggesting that excessive expression of this enzyme may be lethal during gestation. Serum fatty acid analysis of fat-1 transgenic mice (AP-3) fed a high n-6 unsaturated fat (HUSF) diet had an n-6/n-3 fatty acid ratio reduced by 23% (P < 0.025) and the n-3 fatty acid eicosapentaenoic acid (EPA) concentration increased by 61% (P < 0.020). Docosahexaenoic acid (DHA) was increased by 19% (P < 0.015) in white adipose tissue. Male AP-3-fat-1 line of mice had improved glucose tolerance and reduced body weight with no change in insulin sensitivity when challenged with a high-carbohydrate (HC) diet. In contrast, the female AP-3 mice had reduced glucose tolerance and no change in insulin sensitivity or body weight. These findings indicate that male transgenic fat-1 mice have improved glucose tolerance likely due to increased insulin secretion while female fat-1 mice have reduced glucose tolerance compared to wild-type mice. Finally the inability of fat-1 transgenic mice to generate homozygous offspring suggests that prolonged exposure to increased concentrations of n-3 fatty acids may be detrimental to reproduction.
Igarashi, Miki; Kim, Hyung-Wook; Gao, Fei; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I.
Docosapentaenoic acid (DPAn-6, 22:5n-6) is an n-6 polyunsaturated fatty acid (PUFA) whose brain concentration can be increased in rodents by dietary n-3 PUFA deficiency, which may contribute to their behavioral dysfunction. We used our in vivo intravenous infusion method to see if brain DPAn-6 turnover and metabolism also were altered with deprivation. We studied male rats that had been fed for 15 weeks post-weaning an n-3 PUFA adequate diet containing 4.6% alpha-linolenic acid (α-LNA, 18:3n-3) or a deficient diet (0.2% α-LNA), each lacking docosahexaenoic acid (22:6n-3) and arachidonic acid (AA, 20:4n-6). [1-14C]DPAn-6 was infused intravenously for 5 min in unanesthetized rats, after which the brain underwent high-energy microwaving, and then was analyzed. The n-3 PUFA deficient compared with adequate diet increased DPAn-6 and decreased DHA concentrations in plasma and brain, while minimally changing brain AA concentration. Incorporation rates of unesterified DPAn-6 from plasma into individual brain phospholipids were increased 5.2–7.7 fold, while turnover rates were increased 2.1–4.7 fold. The observations suggest that increased metabolism and brain concentrations of DPAn-6 and its metabolites, together with a reduced brain DHA concentration, contribute to behavioral and functional abnormalities reported with dietary n-3 PUFA deprivation in rodents. PMID:22142872
Almukadi, Haifa; Wu, Hui; Böhlke, Mark; Kelley, Charles J; Maher, Timothy J; Pino-Figueroa, Alejandro
The Peruvian plant Lepidium meyenii (Maca) has been shown to possess neuroprotective activity both in vitro and in vivo. Previous studies have also demonstrated the activity of the pentane extract and its macamides, the most representative lipophilic constituents of Maca, in the endocannabinoid system as fatty acid amide hydrolase (FAAH) inhibitors. One of the most active macamides, N-3-methoxybenzyl-linoleamide, was studied to determine its mechanism of interaction with FAAH and whether it has inhibitory activity on mono-acyl glycerol lipase (MAGL), the second enzyme responsible for endocannabinoid degradation. Macamide concentrations from 1 to 100 μM were tested using FAAH and MAGL inhibitor assay methods and showed no effect on MAGL. Tests with other conditions were performed in order to characterize the inhibitory mechanism of FAAH inhibition. N-3-methoxybenzyl-linoleamide displayed significant time-dependent and dose-dependent FAAH inhibitory activity. The mechanism of inhibition was most likely irreversible or slowly reversible. These results suggest the potential application of macamides isolated from Maca as FAAH inhibitors, as they might act on the central nervous system to provide analgesic, anti-inflammatory, or neuroprotective effects, by modulating the release of neurotransmitters.
Ahn, Jinhee; Park, Seo Kwang; Park, Tae Sik; Kim, Jin Hee; Yun, Eunyoung; Kim, Sang-Pil; Lee, Hye Won; Oh, Jun-Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Lee, Sang Yeoup
Background and Objectives Statins remain the mainstay of secondary coronary artery disease (CAD) prevention, but n-3 polyunsaturated fatty acids (ω-3 PUFA) display biological effects that may also reduce the risk of atherosclerosis and CAD. However, data on the possible antiatherosclerotic benefits of adding ω-3 PUFA to statin therapy are limited. This study aimed to investigate the potential additive effects of ω-3 PUFA on regression of atherosclerosis in CAD patients receiving statin therapy and stent implantation. Subjects and Methods Seventy-four CAD patients undergoing percutaneous coronary intervention (PCI) with stent implantation were enrolled, prescribed statins, and randomly assigned to two groups: n-3 group (ω-3 PUFA 3 g/day, n=38) or placebo group (placebo, n=36). All patients completed the study follow-up consisting of an intravascular ultrasound at baseline and at 12 months. Results There was no difference in the baseline characteristics and distribution of other medications. No significant differences were observed in primary endpoints, including changes in atheroma volume index (−12.65% vs. −8.51%, p=0.768) and percent atheroma volume (−4.36% vs. −9.98%, p=0.526), and in secondary endpoints including a change in neointimal volume index (7.84 vs. 4.94 mm3/mm, p=0.087). Conclusion ω-3 PUFA had no definite additional effect on the regression of coronary atherosclerosis when added to statin in CAD patients undergoing PCI. PMID:27482256
Friesen, Russell; Innis, Sheila M
We investigated whether maternal fat intake alters amniotic fluid and fetal intestine phospholipid n-6 and n-3 fatty acids. Female rats were fed a 20% by weight diet from fat with 20% linoleic acid (LA; 18:2n-6) and 8% alpha-linolenic acid (ALA; 18:3n-3) (control diet, n = 8) or 72% LA and 0.2% ALA (n-3 deficient diet, n = 7) from 2 wk before and then throughout gestation. Amniotic fluid and fetal intestine phospholipid fatty acids were analyzed at day 19 gestation using HPLC and gas-liquid chromotography. Amniotic fluid had significantly lower docosahexaenoic acid (DHA; 22:6n-3) and higher docosapentaenoic acid (DPA; 22:5n-6) levels in the n-3-deficient group than in the control group (DHA: 1.29 +/- 0.10 and 6.29 +/- 0.33 g/100 g fatty acid; DPA: 4.01 +/- 0.35 and 0.73 +/- 0.15 g/100 g fatty acid, respectively); these differences in DHA and DPA were present in amniotic fluid cholesterol esters and phosphatidylcholine (PC). Fetal intestines in the n-3-deficient group had significantly higher LA, arachidonic acid (20:4n-6), and DPA levels; lower eicosapentaenoic acid (EPA; 20:5n-3) and DHA levels in PC; and significantly higher DPA and lower EPA and DHA levels in phosphatidylethanolamine (PE) than in the control group; the n-6-to-n-3 fatty acid ratio was 4.9 +/- 0.2 and 32.2 +/- 2.1 in PC and 2.4 +/- 0.03 and 17.1 +/- 0.21 in PE in n-3-deficient and control group intestines, respectively. We demonstrate that maternal dietary fat influences amniotic fluid and fetal intestinal membrane structural lipid essential fatty acids. Maternal dietary fat can influence tissue composition by manipulation of amniotic fluid that is swallowed by the fetus or by transport across the placenta.
Narverud, Ingunn; Myhrstad, Mari C. W.; Herzig, Karl-Heinz; Karhu, Toni; Dahl, Tuva B.; Halvorsen, Bente; Ulven, Stine M.; Holven, Kirsten B.
Peptides released from the small intestine and colon regulate short-term food intake by suppressing appetite and inducing satiety. Intake of marine omega-3 (n-3) fatty acids (FAs) from fish and fish oils is associated with beneficial health effects, whereas the relation between intake of the vegetable n-3 fatty acid α-linolenic acid and diseases is less clear. The aim of the present study was to investigate the postprandial effects of a single high-fat meal enriched with vegetable n-3 or a combination of vegetable and marine n-3 FAs with their different unsaturated fatty acid composition on intestinal peptide release and the adipose tissue. Fourteen healthy lean females consumed three test meals with different fat quality in a fixed order. The test meal consisted of three cakes enriched with coconut fat, linseed oil, and a combination of linseed and cod liver oil. The test days were separated by 2 weeks. Fasting and postprandial blood samples at 3 and 6 h after intake were analyzed. A significant postprandial effect was observed for cholecystokinin, peptide YY, glucose-dependent insulinotropic polypeptide, amylin and insulin, which increased, while leptin decreased postprandially independent of the fat composition in the high-fat meal. In conclusion, in healthy, young, lean females, an intake of a high-fat meal enriched with n-3 FAs from different origin stimulates intestinal peptide release without any difference between the different fat compositions. PMID:27630989
Bandarra, Narcisa M; Lopes, Paula A; Martins, Susana V; Ferreira, Júlia; Alfaia, Cristina M; Rolo, Eva A; Correia, Jorge J; Pinto, Rui M A; Ramos-Bueno, Rebeca P; Batista, Irineu; Prates, José A M; Guil-Guerrero, José L
In this study, we hypothesized that the incorporation of docosahexaenoic acid (DHA) in tissues will be higher when it is ingested as triacylglycerols (TAG) structured at the sn-2 position, which enhances efficacy and health benefits of dietary DHA n-3 supplementation. Ten-week-old Golden Syrian male hamsters were randomly allocated into 4 dietary groups with 10 animals in each: linseed oil (LSO; control group), fish oil (FO), fish oil ethyl esters (FO-EE), and structured DHA at the sn-2 position of TAG (DHA-SL). After 12 weeks, there were no variations in the hamsters' body composition parameters across dietary groups. The DHA-SL diet had the lowest values of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total lipids, and aspartate aminotransferase activity, whereas the inverse was observed for the FO diet. Glucose was increased in the LSO diet without affecting insulin and insulin resistance markers. Whereas n-3 polyunsaturated fatty acid was increased in the brain of hamsters fed the DHA-SL diet, higher levels of n-6 polyunsaturated fatty acid were observed in the liver and erythrocytes of the LSO. The highest omega-3 index was obtained with the DHA-SL diet. The principal component analyses discriminated DHA from other metabolites and set apart 4 clusters matching the 4 diets. Similarly, liver, erythrocytes, and brain were separated from each other, pointing toward an individual signature on fatty acid deposition. The structured sn-2 position DHA-containing TAG ameliorated blood lipids and fatty acid incorporation, in particular eicosapentaenoic acid and DHA in liver, erythrocytes, and brain, relative to commercially FOs, thus improving the health benefits of DHA due to its higher bioavailability.
de Theije, Caroline G M; van den Elsen, Lieke W J; Willemsen, Linette E M; Milosevic, Vanja; Korte-Bouws, Gerdien A H; Lopes da Silva, Sofia; Broersen, Laus M; Korte, S Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D
Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3 LCPUFA-enriched diet before and during sensitization with whey. Social behaviour, acute allergic skin response and serum immunoglobulins were assessed. Monoamine levels were measured in brain and intestine and fatty acid content in brain. N-3 LCPUFA prevented impaired social behaviour of allergic mice. Moreover, n-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation into the brain and restored reduced levels of prefrontal DA and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid in allergic mice. In addition to these brain effects, n-3 LCPUFA supplementation reduced the allergic skin response and restored decreased intestinal levels of serotonin metabolite 5-hydroxyindoleacetic acid in allergic mice. N-3 LCPUFA may have beneficial effects on food allergy-induced deficits in social behaviour, either indirectly by reducing the allergic response and restoring intestinal 5-HT signalling, or directly by DHA incorporation into neuronal membranes, affecting the DA system. Therefore, it is of interest to further investigate the relevance of food allergy-enhanced impairments in social behaviour in humans and the potential benefits of dietary n-3 LCPUFA supplementation.
This study investigated the role of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFAs) of muscle phospholipids in the regulation of neonatal metabolism. Twenty-eight piglets were weaned at 2 days of age and raised on one of two milk formulas that consisted of either a control formula supplying ...
Meng, Hongzhou; Shen, Yuzhen; Shen, Junhui; Zhou, Feng; Shen, Shengrong; Das, Undurti N
Prostate cancer (PCa) is one of the leading causes of death in the elderly men. Polyunsaturated fatty acids (PUFAs) regulate proliferation of cancer cells. In the present study, we evaluated the effect of various PUFAs on the proliferation and survival of human prostate cancer (PC-3) and human prostate epithelial (RWPE-1) cells in vitro.LA, GLA, AA, ALA, EPA and DHA (linoleic acid, gamma-linolenic acid, arachidonic acid, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid respectively) when tested at 50, 100, 150, and 200 μM inhibited proliferation of RWPE-1 and PC-3 cells, except that lower concentrations of LA (25 μM) and GLA (5, 10 μM) promoted proliferation. Though all fatty acids tested produced changes in the production of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), lipoxin A4 and free radical generation by RWPE-1 and PC-3 cells, there were significant differences in their ability to do so. As expected, supplementation of various n-3 and n-6 fatty acids to RWPE-1 and PC-3 cells enhanced the content of the added fatty acids and their long-chain metabolites in these cells. In contrast to previous results, we did not find any direct correlation between inhibition of cell proliferation induced by various fatty acids and free radical generation. These results suggest that polyunsaturated fatty acids suppress proliferation of normal and tumor cells by a variety of mechanisms that may partly depend on the type(s) of cell(s) being tested and the way these fatty acids are handled by the cells. Hence, it is suggested that more deeper and comprehensive studies are needed to understand the actions of fatty acids on the growth of normal and tumor cells.
Meneses, Flavia; Ney, Jacqueline G; Torres, Alexandre G; Trugo, Nadia M F
The aim of the present study was to evaluate the influence of pregnancy in adolescents on the fatty acid composition of the erythrocyte membrane, which was used as a proxy for status of n-3 and n-6 polyunsaturated fatty acids (PUFA), and also on the composition of plasma non-esterified fatty acids (NEFA) mobilized from the adipose tissue. Two matched groups of healthy adolescents (14-19 years) from Rio de Janeiro, Brazil, were compared: pregnant (n=26; 32.7+/-3.9 weeks of gestation, mean+/-SD) and non-pregnant (n=20). Blood samples were collected after an overnight fast. Mean dietary intakes of total fat and n-3 and n-6 PUFA (energy %) were not different between pregnant and non-pregnant adolescents, and the consumption of food sources of docosahexaenoic acid (DHA) was low. Fasting total NEFA and NEFA 18:2n-6, 18:3n-6 and 20:4n-6 (g/100g fatty acids) were higher in pregnant than in non-pregnant adolescents. Although erythrocyte 20:4n-6 was lower in pregnant adolescents, there were no differences in DHA (g/100g fatty acids), in DHA status indices (22:5n-6/22:4n-6 and 22:6n-3/22:5n-6 ratios) and in the index of n-3+n-6 PUFA status ([Sigman-3+Sigman-6]/[Sigman-7+Sigman-9]) in erythrocytes as compared with those of non-pregnant adolescents. In conclusion, pregnancy did not have an adverse effect on erythrocyte DHA content or on DHA and n-3+n-6 PUFA status indices in the adolescents studied.
Flaiz, Linda; Freire, María; Cofrades, Susana; Mateos, Raquel; Weiss, Jochen; Jiménez-Colmenero, Francisco; Bou, Ricard
The purpose of this study was to compare three different emulsion-based systems, namely simple emulsion, double emulsion and gelled double emulsion, for delivery of n-3 fatty acids (perilla oil at 300g/kg) and hydroxytyrosol (300mg/kg). Considering that their structural differences may affect their physical and oxidative stability, this was studied by storing them at 4°C for 22days in the dark. The results showed that the oxidative status was maintained in all systems by the addition of hydroxytyrosol. However, there was some loss of hydroxytyrosol, mainly during sample storage and during preparation of the gelled double emulsion. Moreover, the antioxidant loss was more pronounced in more compartmentalized systems, which was attributed to their increased surface area. However, the double emulsion was found to be less stable than the gelled emulsion. Overall, the encapsulation of labile compounds in more complex systems needs to be carefully studied and adapted to specific technological and/or nutritional requirements.
Schneedorferová, Ivana; Tomčala, Aleš; Valterová, Irena
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.
Monk, Jennifer M.; Turk, Harmony F.; Liddle, Danyelle M.; De Boer, Anna A.; Power, Krista A.; Ma, David W.L.; Robinson, Lindsay E.
Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA) may have utility in mitigating the severity of obesity-associated inflammation and breast cancer. PMID:25360510
Lalia, Antigoni Z.; Johnson, Matthew L.; Jensen, Michael D.; Hames, Kazanna C.; Port, John D.
OBJECTIVE Dietary n-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevent insulin resistance and stimulate mitochondrial biogenesis in rodents, but the findings of translational studies in humans are thus far ambiguous. The aim of this study was to evaluate the influence of EPA and DHA on insulin sensitivity, insulin secretion, and muscle mitochondrial function in insulin-resistant, nondiabetic humans using a robust study design and gold-standard measurements. RESEARCH DESIGN AND METHODS Thirty-one insulin-resistant adults received 3.9 g/day EPA+DHA or placebo for 6 months in a randomized double-blind study. Hyperinsulinemic-euglycemic clamp with somatostatin was used to assess hepatic and peripheral insulin sensitivity. Postprandial glucose disposal and insulin secretion were measured after a meal. Measurements were performed at baseline and after 6 months of treatment. Abdominal fat distribution was evaluated by MRI. Muscle oxidative capacity was measured in isolated mitochondria using high-resolution respirometry and noninvasively by magnetic resonance spectroscopy. RESULTS Compared with placebo, EPA+DHA did not alter peripheral insulin sensitivity, postprandial glucose disposal, or insulin secretion. Hepatic insulin sensitivity, determined from the suppression of endogenous glucose production by insulin, exhibited a small but significant improvement with EPA+DHA compared with placebo. Muscle mitochondrial function was unchanged by EPA+DHA or placebo. CONCLUSIONS This study demonstrates that dietary EPA+DHA does not improve peripheral glucose disposal, insulin secretion, or skeletal muscle mitochondrial function in insulin-resistant nondiabetic humans. There was a modest improvement in hepatic insulin sensitivity with EPA+DHA, but this was not associated with any improvements in clinically meaningful outcomes. PMID:25852206
Sontrop, Jessica; Avison, William R; Evers, Susan E; Speechley, Kathy N; Campbell, M Karen
An inverse association between depression and the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), primarily obtained from fish consumption, is observed in both observational and experimental research and is biologically plausible. Study objectives were to examine whether prenatal depressive symptoms were associated with lower intakes of fish or EPA+DHA. Pregnant women (n = 2394) completed a telephone interview between 10 and 22 weeks' gestation in London, Ontario, 2002-05. Depressive symptoms were measured using the Center for Epidemiologic Studies - Depression Scale (CES-D). Intakes of fish and EPA+DHA were measured using a validated food-frequency questionnaire. Sequential multiple regression was used to examine associations of depressive symptoms with intake of fish and EPA+DHA, respectively, while controlling for sociodemographic, health and lifestyle variables. The mean CES-D score was 9.9 (SD 8.0). Intake of EPA+DHA was dichotomised at the median value of 85 mg/day. Fish consumption and intake of EPA+DHA were not associated with prenatal depressive symptoms after adjustment for confounders; however, depressive symptoms were significantly higher for lower intakes of EPA+DHA among current smokers and women of single/separated/divorced marital status. The adjusted difference in CES-D scores between intake categories of EPA+DHA was -2.4 [95% CI -4.2, -0.4] for current smokers and -2.8 [95% CI -5.2, -0.4] for women of single marital status. Although pregnant women may be at risk for low concentrations of EPA and DHA, an association between low intakes of EPA+DHA and increased depressive symptoms was only observed among current smokers and women of single marital status.
Hamazaki, Kei; Harauma, Akiko; Tanabe, Satoru; Namai, Miho; Moriguchi, Toru; Inadera, Hidekuni
The results of several epidemiological studies and clinical trials investigating the effects of n-3 polyunsaturated fatty acids (PUFAs) on antenatal and postnatal depression remain controversial. In a previous case-control study of early pregnancy in Japan, we found an inverse association between eicosapentaenoic acid and risk of psychological distress after adjusting for possible confounders. Here, in a 1:2 matched case-control study, we further investigated the possible relationship between serum n-3 PUFAs and risk of psychological distress in the second and third trimesters of pregnancy. The psychological distress group (n=71) consisted of subjects with a score of ≥13 on the Kessler Psychological Distress Scale. The control group (n=142) was matched for age, educational level, and family income. Fatty acid composition of total lipid was determined from serum samples by gas chromatography. Associations between fatty acid levels and incidence of psychological distress were evaluated by logistic regression. Sixty-six percent of blood samples were collected in the second trimester and the remainder in the third. There were no significant differences in any of the n-3 PUFAs between the two groups. After adjustment for possible confounders, none of the n-3 PUFAs showed an association with risk of psychological distress. Peripheral n-3 PUFA levels might not influence the risk of psychological distress in later pregnancy. Further research is warranted to clarify this finding.
Bernard, Jonathan Y; De Agostini, Maria; Forhan, Anne; de Lauzon-Guillain, Blandine; Charles, Marie-Aline; Heude, Barbara
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.
Paoli, Antonio; Moro, Tatiana; Bosco, Gerardo; Bianco, Antonino; Grimaldi, Keith A.; Camporesi, Enrico; Mangar, Devanand
Background: the ketogenic diet (KD) has become a widely used nutritional approach for weight loss. Some of the KD’s positive effects on metabolism and cardiovascular risk factors are similar to those seen after n-3 polyunsaturated fatty acids (ω-3) supplementation. We hypothesized that a ketogenic Mediterranean diet with phytoextracts combined with ω-3 supplementation may have increased positive effects on cardiovascular risk factors and inflammation. Methods: We analyzed 34 male overweight subjects; aged between 25 and 65 years who were overall healthy apart from overweight. The subjects followed a ketogenic diet protocol for four weeks; with (KDO3) or without (KD) ω-3 supplementation. Results: All subjects experienced a significant loss of body weight and body fat and there was no significant differences between treatment (body weight: KD—4.7 kg, KDO3—4.03 kg, body fat KD—5.41 kg, KDO3—5.86 kg). There were also significant decreases in total cholesterol, LDL-c, and glucose levels. Triglycerides and insulin levels decreased more in KDO3 vs. KD subjects, with a significant difference. All the investigated inflammatory cytokines (IL-1β, IL-6, TNF-α) decreased significantly in KDO3 subjects whilst only TNF-α showed a significant decrease in KD subjects over the 12 month study period. No significant changes were observed in anti-inflammatory cytokines (IL-10 and IL-1Ra), creatinine, urea and uric acid. Adiponectin increased significantly only in the KDO3 group. Conclusions: ω-3 supplementation improved the positive effects of a ketogenic Mediterranean diet with phytoextracts on some cardiovascular/metabolic risk factors and inflammatory state. PMID:25689563
Trebušak, Tina; Levart, Alenka; Salobir, Janez; Pirman, Tatjana
The objective of the present study was to evaluate the effect of Ganoderma lucidum (Reishi mushroom) or Olea europaea (olive tree) leaves on oxidative stability of rabbit meat fortified with n-3 fatty acids. Forty-eight slovenska kunka (SIKA) rabbits were divided into four homogeneous groups. The control group (CONT-) received diet with 6% palm fat; other groups received diet with 6% linseed oil and were either unsupplemented (CONT+) or supplemented with 1% of G. lucidum (REISHI) or O. europaea leaves (OLIVE). Rabbits were slaughtered and fatty acid composition, concentration of vitamin E and malondialdehyde (MDA) in back muscle were analyzed. The results showed that linseed oil addition improved fatty acid composition by increasing polyunsaturated fatty acid (PUFA) proportion, decreasing proportion of saturated fatty acid (SFA) and reducing n-6/n-3 ratio in rabbit meat. Groups that were supplemented with linseed oil had lower content of α-tocopherol and higher content of γ-tocopherol, compared to the CONT- group. The addition of potential antioxidants did not effectively prevent oxidation of rabbit meat.
Barcelli, U O; Beach, D C; Thompson, B; Weiss, M; Pollak, V E
The nephrotic syndrome was induced in rats by intravenous adriamycin (3 mg/kg). The rats were then divided into four groups which, for six weeks, were pair-fed diets containing beef tallow (BT), fish oil (FO), a source of n-3 fatty acids, evening primrose oil (EPO), a source of n-6 fatty acids, or a combination of evening primrose oil and fish oil, 75:25 (EPO:FO). The fat content of the diets was 15%. Significant incorporation of the fatty acids into kidney phospholipids was demonstrated. Diets containing FO, EPO and EPO:FO lowered plasma triglycerides and total cholesterol levels as compared with diets containing BT. Only EPO:FO raised high density lipoprotein (HDL) cholesterol levels, as compared with BT. The combination EPO:FO prevented the tenfold suppression of aortic 6-keto-PGF1 alpha caused by FO. These changes in plasma lipids and eicosanoid production are potentially antiatherogenic and may prevent glomerular sclerosis. The combination of EPO and FO, containing n-6 and n-3 fatty acids may offer advantages over either family of fatty acids in this model of nephrotic syndrome.
Nassar, B A; Huang, Y S; Manku, M S; Das, U N; Morse, N; Horrobin, D F
The interrelations between linoleic acid (LA) metabolites and fish oil fatty acids were studied. Sprague-Dawley rats (200-220 g) were fed a fat-free semisynthetic diet supplemented with 10% (by weight) of different combinations of evening primrose oil (EPO), a rich source of LA and gamma-linolenic acid, and polepa (POL), a marine oil rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. The combinations of supplement were as follows: 9% EPO-1% POL, 8% EPO-2% POL, 7% EPO-3% POL, 6% EPO-4% POL and 5% EPO-5% POL. After two weeks on the respective diets, the animals were killed, and the fatty acid compositions of liver and plasma phospholipids were examined. The results showed that animals fed higher proportions of POL consistently contained higher levels of dihomo-gamma-linolenic acid (DGLA) (p less than 0.05), a metabolite of LA and GLA, and lower levels of arachidonic acid (AA) (p less than 0.01), a metabolite of DGLA through delta-5-desaturation. Thus, an inverse relationship between AA/DGLA ratio and EPA levels was found to exist (r = -0.765 in plasma and -0.792 in liver). However, there was no such relationship between AA/DGLA ratio and DHA levels. This result suggested that EPA but not DHA in fish oil exerts an inhibitory effect on the conversion of DGLA to AA.
Gatta, Valentina; Scoditti, Egeria; Pellegrino, Mariangela; Carluccio, Maria Annunziata; Calabriso, Nadia; Buonomo, Tonia; Stuppia, Liborio; Storelli, Carlo; De Caterina, Raffaele
Scope High intakes of n-3 fatty acids exert anti-inflammatory effects and cardiovascular protection, but the underlying molecular basis is incompletely defined. By genome-wide analysis we searched for novel effects of docosahexaenoic acid (DHA) on gene expression and pathways in human vascular endothelium under pro-inflammatory conditions. Methods and Results Human umbilical vein endothelial cells were treated with DHA and then stimulated with interleukin(IL)-1β. Total RNA was extracted, and gene expression examined by DNA microarray. DHA alone altered the expression of 188 genes, decreasing 92 and increasing 96. IL-1β changed the expression of 2031 genes, decreasing 997 and increasing 1034. Treatment with DHA before stimulation significantly affected the expression of 116 IL-1β-deregulated genes, counter-regulating the expression of 55 genes among those decreased and of 61 among those increased. Functional and network analyses identified immunological, inflammatory and metabolic pathways as the most affected. Newly identified DHA-regulated genes are involved in stemness, cellular growth, cardiovascular system function and cancer, and included cytochrome p450 4F2(CYP4F2), transforming growth factor(TGF)-β2, Cluster of Differentiation (CD)47, caspase recruitment domain(CARD)11 and phosphodiesterase(PDE)5α. Conclusions Endothelial exposure to DHA regulates novel genes and related pathways. Such unbiased identification should increase our understanding of mechanisms by which n-3 fatty acids affect human diseases. PMID:26114549
Zhuang, Jia-Yuan; Chen, Zhi-Yao; Zhang, Tao; Tang, Du-Peng; Jiang, Xiao-Ying; Zhuang, Ze-Hao
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/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-kbp50, 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. PMID:28134235
Nassar, B A; Das, U N; Huang, Y S; Ells, G; Horrobin, D F
The effect of dietary fats on essential fatty acid metabolism in rats subjected to chemically induced hepatocarcinogenesis was studied. Sixty male rats were fed a diet supplemented with one of the following three oil compositions: 10% hydrogenated coconut oil (HCO); 5% hydrogenated coconut oil and 5% gamma-linolenic acid (18:3n-6)-rich evening primrose oil (EPO); or 5% hydrogenated coconut oil and 5% marine oil (FO). Half of the animals in each dietary regimen were subjected to hepatocarcinogenesis induction using diethylnitrosamine and 2-acetylaminofluorene (2-AAF) followed by partial hepatectomy, whereas the other half underwent hepatectomy without receiving diethylnitrosamine and 2-acetylaminofluorene. Liver phospholipid composition was analyzed. In comparison to the HCO group, the EPO group showed raised levels of arachidonic acid (20:4n-6) and suppressed n-3 fatty acids. The FO group, on the other hand, showed suppressed levels of n-6 and increased n-3 fatty acids. Hepatocarcinogenesis suppressed the level of 20:4n-6 and this effect was greater in the FO rats. The levels of dihomo-gamma-linolenic acid (20:3n-6) were increased by the hepatocarcinogenic treatment, and this effect was further accentuated in the EPO rats. These results suggest that hepatocarcinogenesis may suppress the activity of delta-5-desaturase, which may be one of the reasons why tumor cell membranes have low levels of long chain fatty acids, especially 20:4n-6 cells, and have an impaired capacity to undergo lipid peroxidation.
Jayasinghe, Chamila; Gotoh, Naohiro; Wada, Shun
This study investigated the oxidative stability of n-3 highly unsaturated fatty acid (n-3 HUFA) rich (35% n-3 HUFA) oil-in-water emulsions (10 wt% oil) with commercial antioxidants and natural plant extracts. Ascorbic acid, α-tocopherol, and the extracts of Indian gooseberry fruit (Emblica officinalis) (IGFE) and sweet basil leaves (Ocimum basilicum L.) (SBLE) were used for the study as antioxidants. The progress of oxidation in the systems was evaluated at 35 °C over 120 h against a control (without antioxidant) by monitoring the formation of primary (conjugated dienes) and secondary (volatile carbonyl compounds) oxidation products. Volatile carbonyl compounds were trapped as derivatives of pentafluorophenyl hydrazine and quantified by headspace solid-phase microextraction analysis. About 40 volatile carbonyls were successfully identified by this method. trans,trans-2,4-Heptadienal, trans,cis-2,4-heptadienal, 3,5-octadien-2-one, and 1-penten-3-ol were predominant. The volatile carbonyl compounds and conjugated dienes were formed at low rates in emulsion systems in which α-tocopherol and natural plant extracts had been introduced, compared to the control. Emulsion systems containing ascorbic acid showed low stability, as indicated by the oxidation products that were formed at high rates compared to the control. These results indicated that ascorbic acid activated the oxidation reactions in n-3 HUFA rich water emulsions, while natural plant extracts that were rich in polyphenols and α-tocopherol were active as antioxidants. The present study further demonstrated the applicability of the polar paradox theory in the determination of stability for n-3 HUFA rich water emulsions with commercial antioxidants and natural plant extracts.
Without dietary sources of long chain (LC) n-3 fatty acids, alpha-linolenic acid (ALA;18:3n-3) is the precursor for docosahexaenoic acid (DHA; 22:6n-3). It is not known how energy restriction (ER) impacts ALA conversion to DHA. We tested the hypothesis that ER reduces LCn-3 content in growing rats ...
Andreeva, Valentina A.; Latarche, Clotilde; Hercberg, Serge; Briançon, Serge; Galan, Pilar; Kesse-Guyot, Emmanuelle
Background Despite growing attention to nutrition and quality of life in cardiovascular disease survivors, the impact of dietary factors according to disease type or to quality of life domain is poorly understood. We investigated the effects of B vitamin and/or n-3 fatty acid supplementation on health-related quality of life among survivors of stroke, myocardial infarction, or unstable angina. Methods We performed ancillary analyses of the SU.FOL.OM3 trial (2003–2009; France). In total, 2,501 men (mean age = 61 y) and women (mean age = 63 y) were randomized in a 2×2 factorial design to: 1) 0.56 mg 5-methyl-tetrahydrofolate, 3 mg vitamin B6, 0.02 mg vitamin B12; 2) 600 mg eicosapentaenoic and docosahexaenoic acids in a 2∶1 ratio; 3) B vitamins and n-3 fatty acids combined; or 4) placebo. Health-related quality of life was evaluated at follow-up with the Medical Outcomes Study 36-Item Short Form Health Survey. Data from 2,029 individuals were used in this analysis. Results After 3.1±0.4 y, no effects of supplementation with either B vitamins or n-3 fatty acids on quality of life (physical or mental health domains) were found. However, participants receiving B vitamins had slightly more activity limitations due to emotional problems compared with those not receiving B vitamins (mean difference = 3.8; 95% CI: 0.4, 7.1). A significant interaction of treatment by prior disease revealed an inverse association between n-3 fatty acids and vitality among myocardial infarction survivors (mean difference = 2.9; 95% CI: 0.5, 5.2). Conclusions There were no beneficial effects of supplementation with relatively low doses of B vitamins or n-3 fatty acids on health-related quality of life in cardiovascular disease survivors. The adverse effects of B vitamins on activity limitations and of n-3 fatty acids on vitality among individuals with prior myocardial infarction merit confirmation. PMID:24465438
Schmidt, E B; Nielsen, L K; Pedersen, J O; Kornerup, H J; Dyerberg, J
We have studied the effect of dietary supplementation with 4 g of n-3 polyunsaturated fatty acids (n-3 PUFA) daily for 6 wk on plasma lipids, haemostasis and monocyte chemotaxis in 10 patients with untreated hypertension. Total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides did not change, but the ratio of total to HDL-cholesterol was significantly reduced after the fish oil supplement. Platelet function was unaltered by intake of n-3. Plasma fibrinogen and fibronectin decreased after supplementation with n-3 PUFA, while the effects on fibrinolysis were equivocal. Monocyte chemotaxis was reduced by the supplement. These data lend support to a role for an increased intake of n-3 PUFA in the management of patients with hypertension.
Otten, W; Iaizzo, P A; Eichinger, H M
Knowledge concerning the genetic defects underlying malignant hyperthermia (MH) has expanded rapidly in recent years. In contrast, our understanding of the accompanying physiological changes is less clear. In this regard, the aim of this study was to determine whether normal swine and swine susceptible to MH (both heterozygous and homozygous animals) differ in their abilities to incorporate n-3 (omega 3) fatty acids into their skeletal and heart muscles. Swine of each genotype were fed either a diet rich in n-3 fatty acids (i.e., 5% fish oil) or an equal caloric diet low in n-3 fatty acids (i.e., 5% coconut oil). All dietary supplementations were given over a 13-week period. Subsequently, for each muscle type the following was determined: 1) the relative fatty acid profiles of eight different phospholipid classes and of neutral lipids, and 2) the total phospholipid and the total lipid content. The incorporation of n-3 fatty acids (i.e., eicosapentaenoic acid and docosahexaenoic acid) occurred within the various phospholipids and neutral lipids without influencing their total lipid content. The increased content of n-3 fatty acids in neutral lipids of skeletal muscle was related to a decreased content of medium-chain saturated fatty acids, whereas an increased incorporation of n-3 fatty acids into the membrane phospholipids was often related to a decreased content of linoleic acid and/or arachidonic acid. In general, the pattern of n-3 fatty acid incorporation was considerably different between the normal animals and the MH homozygous and heterozygous animals. The significant interaction between diet-induced n-3 fatty acid profiles and the stress-susceptible MH genotype may indicate an altered mechanism for fatty acid turnover and a repair mechanism to maintain cellular functions and structure.
Reddy, K Vijay Kumar; Naidu, K Akhilender
Our recent study has demonstrated that medium chain triglycerides (MCT) and monounsaturated fatty acids potentiate the beneficial effects of fish oil on risk factors of cardiovascular disease. In the present study, we have investigated the influence of MCT or olive oil on the protective and mucosal healing ability of fish oil in ulcerative colitis using cell simulation and animal models. Caco-2 cells grown in medium chain fatty acids enriched medium has exaggerated t-butyl hydroperoxide induced cell damage, GSH depletion, and IL-1β induced IL-8 synthesis, compared to the cells grown in oleic acid & hydroxytyrosol (OT) enriched medium. Further, combined treatment of cells with eicosapentaenoic acid, docosahexaenoic acid, and OT has remarkably attenuated the cell damage, and IL-8 synthesis, compared to individual treatments. To evaluate the effect of these lipid formulations in vivo, adult Wistar rats were fed diet enriched with high amount of medium chain triglycerides (MCT), virgin olive oil, or their combination with fish oil. Colitis was induced in rats using dextran sulfate sodium (DSS) for 7days followed by 10-days of recovery period. Rats of MCT group exhibit severe disease activity, higher levels of inflammatory cytokines in the colon compared to the olive oil group. Furthermore, there was persistent body weight loss, loose stools, higher levels of inflammatory cytokines in the rats of MCT group, even after DSS was withdrawn from drinking water. Conversely, fish oil has remarkably attenuated the DSS induced alterations in both MCT and olive oil diet groups with significantly greater effect in the olive oil group. Thus, MCT increase the susceptibility to colitis through oxidative damage and IL-8 synthesis in intestinal epithelial cells. The beneficial effects of virgin olive oil could be partially attributed to hydroxytyrosol. Combined treatment of hydroxytyrosol, oleic acid and n-3 fatty acids exhibit huge therapeutic benefits in colitis.
An, Lei; Pang, Yun-Wei; Gao, Hong-Mei; Tao, Li; Miao, Kai; Wu, Zhong-Hong; and others
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 controlled 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.
Bagge, Carina N; Strandhave, Charlotte; Skov, Charlotte M; Svensson, My; Schmidt, Erik B; Christensen, Jeppe H
Marine long-chained n-3 polyunsaturated fatty acids (PUFA) are recognized for their cardio-protective effects, including potential lowering of blood pressure. We hypothesized that higher habitual fish intake and n-3 PUFA plasma levels were associated with lower blood pressure and being less likely to receive antihypertensive medication after one-year follow-up. In this prospective study of 115 patients, we assessed 24 h ambulatory and central blood pressure, plasma phospholipid fatty acid composition using gas chromatography and participants completed a food frequency questionnaire, including fish-eating habits. All measurements were repeated at one-year follow-up. At baseline, patients consuming fish ≥2 times per month for dinner had significantly higher plasma levels of total marine n-3 PUFA, docosahexaenoic acid and eicosapentaenoic acid as well as significantly lower central blood pressure and a trend towards lower peripheral blood pressure. At follow-up, 21 patients (18%) without antihypertensive medication had significantly higher plasma levels of n-3 PUFA, docosahexaenoic acid and eicosapentaenoic acid as well as a higher, but still acceptable 24 h ambulatory blood pressure (137/85 mmHg) compared to subjects receiving antihypertensive medication. The untreated group was more prone to take fish oil capsules and increased their plasma levels of n-3 PUFA compared to baseline. In patients with newly diagnosed, untreated hypertension, regular fish consumption was accompanied by lower blood pressure. After one year, patients without antihypertensive medication were characterized by a significant increase and higher plasma levels of n-3 PUFA. This supports a blood pressure-lowering effect and suggests an increase in marine n-3 PUFA intake as part of non-pharmacological treatment of hypertension.
Sundaram, Sneha; Bukowski, Michael R; Lie, Wen-Rong; Picklo, Matthew J; Yan, Lin
Dysregulation of adipokines is a hallmark of obesity. Polyunsaturated fatty acids in fish oil may exert anti-inflammatory effects on adipose tissue mitigating the dysregulation of adipokines thereby preventing obesity. This study investigated the effects of high-fat diets containing different amounts of n3 polyunsaturated fatty acids (PUFA) on adiposity and adipokine production in mice. Mice were fed a low-fat or a high-fat diet with 16 or 45 % of energy from corn oil (low n3 PUFA) in comparison with a high-fat diet containing soybean or high-oleic sunflower oil (adequate n3 PUFA) or flaxseed or fish oil (high n3 PUFA) for 11 weeks. High-fat diets, regardless of types of oils, significantly increased body fat mass and body weights compared to the low-fat diet. Adipose fatty acid composition and contents reflected dietary fatty acid profiles. The high-fat fish oil diet significantly increased adiponectin and reduced leptin concentrations in both plasma and adipose tissue; it did not elevate plasma insulin concentration compared to the high-fat corn oil diet. All high-fat diets elevated concentrations of plasminogen activator inhibitor-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP-1) but lowered resistin concentrations in both plasma and adipose tissue. In conclusion, fish oil may be beneficial in improving insulin sensitivity by upregulation of adiponectin and downregulation of leptin production; n3 and n6 PUFA do not play a role at the dietary levels tested in reducing adiposity and production of pro-inflammatory cytokines (leptin, PAI-1, MCP-1 and resistin) and anti-inflammatory cytokine adiponectin.
van der Meij, Barbara S; Langius, Jacqueline A E; Smit, Egbert F; Spreeuwenberg, Marieke D; von Blomberg, B Mary E; Heijboer, Annemieke C; Paul, Marinus A; van Leeuwen, Paul A M
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P < 0.05), a better FFM maintenance after 3 and 5 wk (B = 1.5 and 1.9 kg, respectively; P < 0.05), a reduced REE (B = -16.7% of predicted; P = 0.01) after 3 wk, and a trend for a greater MUAC (B = 9.1; P = 0.06) and lower interleukin-6 production (B = -27.9; P = 0.08) after 5 wk. After 4 wk, the I group had a higher energy and protein intake than the C group (B = 2456 kJ/24 h, P = 0.03 and B = 25.0 g, P = 0.01, respectively). In conclusion, a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC.
Muldoon, Matthew F.; Erickson, Kirk I.; Goodpaster, Bret H.; Jakicic, John M.; Conklin, Sarah M.; Sekikawa, Akira; Yao, Jeffrey K.; Manuck, Stephen B.
Greater consumption of n3 (ω3) polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce risk for cardiovascular disease events, yet their effects on metabolic risk factors and diabetes remain unclear. This cross-sectional study used a community volunteer sample to test whether the associations between n3 fatty acids and cardiometabolic risk vary as a function of physical activity. Participants were 344 generally healthy adults, 30–54 y of age, not taking fish oil supplements or confounding medications. Serum phospholipid EPA and DHA were used together (EPA+DHA) as a biomarker of n3 fatty acid exposure. Cardiometabolic risk was calculated as a continuous measure based on standardized distributions of blood pressure, waist circumference, HDL cholesterol, triglycerides, glucose, and a simple count of risk factors. Insulin resistance was estimated from the homeostatic model assessment. Physical activity was found to predict cardiometabolic risk (P ≤ 0.02) and insulin resistance (P ≤ 0.02) and to moderate the association between EPA+DHA and both cardiometabolic risk (P-interaction ≤ 0.02) and insulin resistance (P-interaction ≤ 0.02). Specifically, higher EPA+DHA was associated with lower cardiometabolic risk and insulin resistance in persons engaged in regular physical activity but not in relatively inactive individuals. These findings were noted in several components of cardiometabolic risk, in men and women separately, and in models adjusted for overall diet quality. In midlife adults, habitual physical activity may be necessary to unmask the salutary effects of n3 fatty acids on cardiometabolic risk and insulin resistance. PMID:23884386
Wang, Yi; Goodrich, Jaclyn M.; Werner, Robert; Gillespie, Brenda; Basu, Niladri; Franzblau, Alfred
Background Some clinical studies have suggested that ingestion of n-3 polyunsaturated fatty acids (PUFA) has neuroprotective effects on peripheral nerve function. However, few epidemiological studies have examined the effect of dietary n-3 PUFA intake from fish consumption on peripheral nerve function, and none have controlled for co-occurrence of methylmercury exposure from fish consumption. Objectives We evaluated the effect of estimated dietary n-3 PUFA intake on peripheral nerve function after adjusting for biomarkers of methylmercury and elemental mercury in a convenience sample of 515 dental professionals. Methods We measured sensory nerve conduction (peak latency and amplitude) of the median, ulnar and sural nerves and total mercury concentrations in hair and urine samples. We estimated daily intake (mg/day) of the total n-3 PUFA, n-3 docosahexaenoic acid (DHA), and n-3 eicosapentaenoic acid (EPA) based on a self-administrated fish consumption frequency questionnaire. We also collected information on mercury exposure, demographics and other covariates. Results The estimated median intakes of total n-3 PUFA, n-3 EPA, and n-3 DHA were 447, 105, and 179 mg/day, respectively. The mean mercury concentrations in urine (1.05μg/L) and hair (0.49μg/g) were not significantly different from the US general population. We found no consistent association between n-3 PUFA intake and sensory nerve conduction after adjusting for mercury concentrations in hair and urine although some positive associations were observed with the sural nerve. Conclusions In a convenience sample of dental professionals, we found little evidence suggesting that dietary intake of n-3 PUFAs from fish has any impact on peripheral nerve function after adjustment for methylmercury exposure from fish and elemental mercury exposure from dental amalgam. PMID:23538138
Pala, Valeria; Russo, Paola; Risé, Patrizia; Moreno, Luis A.; De Henauw, Stefaan; Mehlig, Kirsten; Veidebaum, Toomas; Molnár, Denés; Tornaritis, Michael; Galli, Claudio; Ahrens, Wolfgang; Börnhorst, Claudia
Background Polyunsaturated n-3 and n-6 polyunsaturated fatty acids (PUFA) are precursors of biologically active metabolites that affect blood pressure (BP) regulation. This study investigated the association of n-3 and n-6 PUFA and BP in children and adolescents. Methods In a subsample of 1267 children aged 2–9 years at baseline of the European IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort whole blood fatty acids were measured by a validated gas chromatographic method. Systolic and diastolic BP was measured at baseline and after two and six years. Mixed-effects models were used to assess the associations between fatty acids at baseline and BP z-scores over time adjusting for relevant covariables. Models were further estimated stratified by sex and weight status. Results The baseline level of arachidonic acid was positively associated with subsequent systolic BP (β = 0.08, P = 0.002) and diastolic BP (β = 0.07, P<0.001). In thin/normal weight children, baseline alpha-linolenic (β = -1.13, P = 0.003) and eicosapentaenoic acid (β = -0.85, P = 0.003) levels were inversely related to baseline and also to subsequent systolic BP and alpha-linolenic acid to subsequent diastolic BP. In overweight/obese children, baseline eicosapentaenoic acid level was positively associated with baseline diastolic BP (β = 0.54, P = 0.005). Conclusions Low blood arachidonic acid levels in the whole sample and high n-3 PUFA levels in thin/normal weight children are associated with lower and therefore healthier BP. The beneficial effects of high n-3 PUFA on BP were not observed in overweight/obese children, suggesting that they may have been overlaid by the unfavorable effects of excess weight. PMID:27806134
Baek, Dawon; Park, Yongsoon
Associations between n-3 polyunsaturated fatty acids (PUFAs), inflammation, oxidative stress and the risk of depression have been suggested. We hypothesize that erythrocyte n-3 PUFAs are inversely associated with biomarkers for inflammation and oxidative stress in Koreans with and without depression. Study participants comprised 80 cases diagnosed with depression based on the Center for Epidemiological Studies Depression Scale Korea version (CES-D-K) scores ≥25 and psychiatrist confirmation and 80 age- and sex-matched healthy controls without histories of depression. Depressed patients had lower levels of n-3 PUFAs and higher circulating levels of inducible nitric oxide synthase (iNOS), superoxide dismutase, interferon-γ, and nitrotyrosine compared to the controls. CES-D-K scores and levels of iNOS and tumor necrosis factor (TNF)-α were negatively associated with Omega-3 Index (erythrocyte levels of eicosapentaenoic acid and docosahexaenoic acid) after adjusting for confounding factors. Concentrations of iNOS, TNF-α, thiobarbituric acid reactive substances, and nitrotyrosine were negatively correlated with erythrocyte levels of n-3 PUFAs, but positively with erythrocyte levels of n-6 PUFAs. Erythrocyte levels of n-3 PUFAs were inversely associated with circulating markers of inflammation and oxidative stress in Koreans with and without depression in this case control study. Future randomized controlled trials are needed to determine whether dietary or supplemental n-3 PUFAs can reduce inflammation and oxidative stress, and reduce depressive symptoms in humans.
Elis, Sebastien; Desmarchais, Alice; Freret, Sandrine; Maillard, Virginie; Labas, Valérie; Cognié, Juliette; Briant, Eric; Hivelin, Celine; Dupont, Joëlle; Uzbekova, Svetlana
The objective of this study was to determine whether fish oil supplement has an effect on adipose tissue lipid profiles and gene expression in postpartum dairy cows. Holstein cows were supplemented with either long-chain n-3 polyunsaturated fatty acid (PUFA; protected fish oil) or control PUFA (n-6; toasted soybeans) for 2mo after calving (n=23 per diet). These cows showed no difference in milk production or metabolic parameters, but exhibited a tendency toward a decrease in early embryo mortality rate after artificial insemination. We hypothesized that, in addition to this effect, modifications in adipose tissue (AT) gene expression and lipid profiles would occur in response to diet. Subcutaneous AT samples were thus collected from the dewlaps of n-3 and n-6 dairy cows at 1mo antepartum, and 1wk, 2mo, and 5mo postpartum for the analysis of lipids and gene expression. Lipid profiles were obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in both positive and negative modes. We found 37 lipid species in the 200 to 1,200 m/z range, which differed between the n-3 and control groups, suggesting that the n-3 supplement affected the lipid composition through the enrichment of lipids integrating long-chain PUFA from fish oil sources: eicosapentaenoic and docosahexaenoic acid. Moreover, a decrease in triacylglycerolipids was observed in AT of n-3 supplemented cows. The expression of 44 genes involved in fatty acid metabolism and the adipokine system was assessed by real-time reverse-transcription PCR. Hierarchical clustering, according to either postpartum stage or diet, enabled us to group genes exhibiting similar kinetic properties during lactation or by those that varied in similar ways after n-3 supplementation, respectively. Among the genes exhibiting a dietary effect, FABP4, LIPE, CD36, and PLIN1 were overexpressed in n-3 AT samples compared with the control, suggesting an increase in lipolysis due to n-3 supplementation, which
Kurt, Asuman; Andican, Gülnur; Siva, Zeynep Oşar; Andican, Ahat; Burcak, Gülden
In diabetes mellitus, chronic hyperglycemia leads to formation of advanced glycation end products (AGEs). Binding of AGEs to receptors of AGE (RAGE) causes deleterious effects. In populations with a high consumption of n-3 long-chain polyunsaturated fatty acids, a lower prevalence of diabetes mellitus has been reported. We aimed to investigate the effects of n-3 fatty acid (EPA and DHA) supplementation on the levels of AGEs (carboxymethyl lysine (CML) and pentosidine), sRAGE, and nuclear factor kappa B (NF-kB) in type 2 diabetes mellitus (T2DM). T2DM patients (n = 38) treated with oral hypoglycemic agents, without insulin were supplemented with n-3 fatty acids (1.2 g/day) for 2 months. Plasma CML, pentosidine, sRAGE, and NF-kB levels were measured by ELISA both before and after the supplementation. n-3 fatty acid supplementation significantly reduced fasting glucose (p < 0.01), glycated hemoglobin (HbA1c) (p < 0.05), and pentosidine (p < 0.05) levels. The supplementation induced percentage changes in pentosidine and HbA1c and in pentosidine and creatinine were observed to be correlated (r = 0.349, p < 0.05) and (r = 0.377, p < 0.05), respectively. Waist circumference and systolic and diastolic pressures were significantly decreased due to n-3 supplementation (p < 0.001, p < 0.01, p < 0.01), respectively. Our results show that supplementation with n-3 fatty acid has beneficial effects on waist circumference; systolic and diastolic blood pressures; and the levels of glucose, HbA1c, and pentosidine in T2DM patients. However, the supplementation failed to decrease these parameters to the reference ranges for healthy subjects. In addition, the supplementation did not appear to induce any significant differences in CML, sRAGE, or NF-kB.
The data supporting a negative effect of dietary trans fatty acids on cardiovascular disease risk is consistent. The primary dietary sources of trans fatty acids include partially hydrogenated fat and rudiment fat. The adverse effect of trans fatty acids on plasma lipoprotein profiles is consisten...
Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Al Mamun, Abdullah; Inoue, Takayuki; Hossain, Shahdat; Arita, Makoto; Shido, Osamu
We investigated whether a highly purified eicosapentaenoic acid (EPA) and a concentrated n-3 fatty acid formulation (prescription TAK-085) containing EPA and docosahexaenoic acid (DHA) ethyl ester could improve the learning ability of aged rats and whether this specific outcome had any relation with the brain levels of EPA-derived eicosanoids and DHA-derived docosanoids. The rats were tested for reference memory errors (RMEs) and working memory errors (WMEs) in an eight-arm radial maze. Fatty acid compositions were analyzed by GC, whereas brain eicosanoid/docosanoids were measured by LC-ESI-MS-MS-based analysis. The levels of lipid peroxides (LPOs) were measured by thiobarbituric acid reactive substances. The administration of TAK-085 at 300 mg·kg⁻¹day⁻¹ for 17 weeks reduced the number of RMEs in aged rats compared with that in the control rats. Both TAK-085 and EPA administration increased plasma EPA and DHA levels in aged rats, with concurrent increases in DHA and decreases in arachidonic acid in the corticohippocampal brain tissues. TAK-085 administration significantly increased the formation of EPA-derived 5-HETE and DHA-derived 7-, 10-, and 17-HDoHE, PD1, RvD1, and RvD2. ARA-derived PGE2, PGD2, and PGF2α significantly decreased in TAK-085-treated rats. DHA-derived mediators demonstrated a significantly negative correlation with the number of RMEs, whereas EPA-derived mediators did not exhibit any relationship. Furthermore, compared with the control rats, the levels of LPO in the plasma, cerebral cortex, and hippocampus were significantly reduced in TAK-085-treated rats. The findings of the present study suggest that long-term EPA+DHA administration may be a possible preventative strategy against age-related cognitive decline.
Juskiewicz, Jerzy; Jankowski, Jan; Zielinski, Henryk; Zdunczyk, Zenon; Mikulski, Dariusz; Antoszkiewicz, Zofia; Kosmala, Monika; Zdunczyk, Przemyslaw
The aim of this study was to determine the efficacy of different dietary fruit pomaces in reducing lipid oxidation in the meat of turkeys fed diets with a high content of n-3 polyunsaturated fatty acids (PUFAs). Over a period of 4 weeks before slaughter, turkeys were fed diets with the addition of 5% dried apple, blackcurrant, strawberry and seedless strawberry pomaces (groups AP, BP, SP and SSP, respectively) and 2.5% linseed oil. Pomaces differed in the content (from 5.5 in AP to 43.1 mg/g in SSP) and composition of polyphenols Proanthocyanidins were the main polyphenolic fraction in all pomaces, AP contained flavone glycosides and dihydrochalcones, BP contained anthocyanins, and SP and SSP—ellagitannins. The n-6/n-3 PUFA ratio in all diets was comparable and lower than 2:1. In comparison with groups C and AP, the percentage of n-3 PUFAs in the total fatty acid pool of white meat from the breast muscles of turkeys in groups BP, SP and SSP was significantly higher, proportionally to the higher content of α-linolenic acid in berry pomaces. The fatty acid profile of dark meat from thigh muscles, including the n-6/n-3 PUFA ratio, was similar and lower than 3:1 in all groups. Vitamin A levels in raw breast muscles were higher in group AP than in groups C and BP (P<0.05). The addition of fruit pomaces to turkey diets lowered vitamin E concentrations (P = 0.001) in raw breast muscles relative to group C. Diets supplemented with fruit pomaces significantly lowered the concentration of thiobarbituric acid reactive substances (TBARS) in raw, frozen and cooked meat. Our results indicate that the dietary application of dried fruit pomaces increases the oxidative stability of meat from turkeys fed linseed oil, and strawberry pomace exerted the most desirable effects due to its highest polyphenol content and antioxidant potential. PMID:28076425
Mamalakis, George; Kiriakakis, Michael; Tsibinos, George; Jansen, Eugene; Cremers, Hans; Strien, Carlo; Hatzis, Christos; Moschandreas, Joanna; Linardakis, Manolis; Kromhout, Daan; Kafatos, Anthony
Studies have shown that depression relates to biomarkers of both short-term and long-term polyunsaturated fatty acid intake. However, it is not known which of these two biomarkers is more closely related to depression. The aim of this study was to examine the relationship of depression with both adipose tissue and serum phospholipid polyunsaturated fatty acids and to assess the importance of each of these two biomarkers in relating to depression. This is a cross-sectional study of healthy adults from the island of Crete. Subjects were examined by the Preventive Medicine and Nutrition Clinic of the University of Crete. Subjects were 394 healthy adults (175 males, 219 females) aged 18-60. The sample consisted of farmers from a number of rural communities of Crete. Fatty acids were determined by gas chromatography in adipose tissue and serum phospholipids. Information about depression was obtained through the Beck Depression Inventory (BDI) and Zung Self-rating Depression Scale (ZSRDS). Adipose tissue alpha-linolenic acid (ALA) (C18:3n-3) was inversely correlated to BDI (r=-0.17, p<0.02). Multiple linear regression analysis taking into account the possible confounding effect of age, gender, body mass index (BMI), smoking and educational level did not confirm this association. The other polyunsaturated fatty acids in adipose tissue were not related to depression. Serum phospholipid polyunsaturated fatty acids did not correlate with depression. This study did not show that the polyunsaturated fatty acids in the adipose tissue are better predictors of depression than those in serum phospholipids.
Cachaldora, P; García-Rebollar, P; Alvarez, C; De Blas, J C; Méndez, J
1. Laying hen performance and yolk fat fatty acid (FA) concentrations were evaluated with respect to the inclusion in the diet of different sources and levels of marine fish oil (MFO). 2. Twelve diets were arranged factorially, with three sources (MFO1, MFO2_EPA, MFO3_DHA) and four levels of inclusion (15, 30, 45 and 60 g/kg) of MFO. 3. Type of diet had little effect on egg production traits, although laying rate and shell thickness slightly decreased at the highest level of MFO supplementation. 4. An increase in level of inclusion of MFO from 15 to 60 g/kg linearly increased concentrations of C20:5 n-3, C22:5 n-3, C22:6 n-3 and total n-3 FA in yolk fat, but greatly impaired their efficiencies of deposition (g retained/g ingested). 5. An interaction between type and dietary concentration of MFO was found, as the reduction in efficiency of retention of n-3 FA in egg fat with level of MFO was less when the proportion of n-3 in total FA decreased or when that of DHA in total n-3 FA increased. 6. MFO3_ DHA was more efficiently used for total n-3 FA yolk deposition than MFO2_EPA at a similar total n-3 FA intake. 7. Dietary inclusion of MFO reduced LC n-6 FA yolk fat content, which additionally decreased the ratio between total n-6 and total n-3 FA in egg fat. 8. Regression equations were calculated in order to predict efficiency of retention and n-3 FA concentration of yolk fat in the range of diets studied.
Leiber, Florian; Kreuzer, Michael; Nigg, Daniel; Wettstein, Hans-Rudolf; Scheeder, Martin Richard Leo
The influence of grass-only diets either from rye-grass-dominated lowland pastures (400 m above sea level) or botanically diverse alpine pastures (2000 m) on the FA profile of milk was investigated using three groups of six Brown Swiss cows each. Two groups were fed grass-only on pasture (P) or freshly harvested in barn (B), both for two experimental periods in the lowlands and, consecutively, two periods on the alp. Group C served as the control, receiving a silage-concentrate diet and permanently staying in the lowlands. Effects of vegetation stage or pasture vs. barn feeding on milk fat composition were negligible. Compared with the control, alpha-linolenic acid (18:3n-3) consumption was elevated in groups P and B (79%; P< 0.001) during the lowland periods but decreased on the alp to the level of C owing to feed intake depression and lower 18:3n-3 concentration in the alpine forage. Average 18:3n-3 contents of milk fat were higher in groups P and B than in C by 33% (P< 0.01) at low and by 96% (P < 0.001) at high altitude, indicating that 18:3n-3 levels in milk were to some extent independent of 18:3n-3 consumption. The cis-9, trans-11 CLA content in milk of grass-fed cows was higher compared with C but lower for the alpine vs. lowland periods whereas the trans-11, cis-13 isomer further increased with altitude. Long-chain n-3 FA and phytanic acid increased while arachidonic acid decreased with grass-only feeding, but none of them responded to altitude. Grass-only feeding increased milk alpha-tocopherol concentration by 86 and 134% at low and high altitude (P < 0.001), respectively. Changes in the ruminal ecosystem due to energy shortage or specific secondary plant metabolites are discussed as possible causes for the high 18:3n-3 concentrations in alpine milk.
Resende, T L; Kraft, J; Soder, K J; Pereira, A B D; Woitschach, D E; Reis, R B; Brito, A F
decreased linearly with GFX supplementation. Milk trans-11 18:1, α-linolenic acid, cis-9,trans-11 18:2, and the sum of n-3 FA all increased linearly and quadratically, whereas the milk ratio of n-6 to n-3 decreased linearly in cows fed GFX. Overall, compared with the control diet (0% GFX), the diet with 15% GFX supplementation resulted in the lowest milk yield but highest milk proportions and yields (data not shown) of cis-9,trans-11 18:2 and n-3 FA.
Hamazaki, Kei; Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Seki, Shoji; Hori, Takeshi; Hamazaki, Tomohito; Kimura, Tomoatsu
Ossification of the posterior longitudinal ligament (OPLL) involves the replacement of ligamentous tissue with ectopic bone. Although genetics and heritability appear to be involved in the development of OPLL, its pathogenesis remains to be elucidated. Given previous findings that 5,8,11-eicosatrienoic acid [20:3n-9, Mead acid (MA)] has depressive effects on osteoblastic activity and anti-angiogenic effects, and that n-3 polyunsaturated fatty acids (PUFAs) have a preventive effect on heterotopic ossification, we hypothesized that both fatty acids would be involved in OPLL development. To examine the biological significance of these and other fatty acids in OPLL, we conducted this case-control study involving 106 patients with cervical OPLL and 109 age matched controls. Fatty acid composition was determined from plasma samples by gas chromatography. Associations between fatty acid levels and incident OPLL were evaluated by logistic regression. Contrary to our expectations, we found no significant differences between patients and controls in the levels of MA or n-3 PUFAs (e.g., eicosapentaenoic acid and docosahexaenoic acid). Logistic regression analysis did not reveal any associations with OPLL risk for MA or n-3 PUFAs. In conclusion, no potential role was found for MA or n-3 PUFAs in ectopic bone formation in the spinal canal.
He, Yongjin; Li, Jingbo; Kodali, Sitharam; Chen, Bilian; Guo, Zheng
Declining quantity/quality of available n-3 polyunsaturated fatty acids (n-3 PUFAs) resources demand innovative technology to concentrate n-3 PUFAs from low quality oils into value-added products/health-beneficial ingredients rich in n-3 PUFAs. This work proposed the catalytic property and specificity of an ideal enzyme required to tackle this task and identified Candida antarctica lipase A (CAL-A) is such a near-ideal enzyme in practice, which concentrates n-3 PUFAs from 25% to 27% in oils to a theoretically closer value 90% in monoacylglycerols (MAGs) via one-step enzymatic ethanolysis. Non-regiospecificity and high non-n-3 PUFAs preference of CAL-A are the catalytic feature to selectively cleave non-n-3 PUFAs in all 3 positions of triacylglycerols (TAGs); while high ethanol/TAGs ratio, low operation temperature and high tolerance to polar ethanol are essential conditions beyond biocatalyst itself. C-13 Nuclear magnetic resonance ((13)C NMR) analysis and competitive factor estimation verified the hypothesis and confirmed the plausible suggestion of catalytic mechanism of CAL-A.
Fernandez, Inés; Pallaro, Anabel N; Slobodianik, Nora H
In the present paper we analyzed the effect caused by different recovery diets enriched with n-3 polyunsaturated fatty acids (PUFA n-3) on thymus and serum lipid pattern. Severe depleted weanling Wistar rats (D) were divided in three groups that received during 10 days a 20% casein diet supplemented with EPA+DHA (group Cas), a 20% protein milk diet prepared using a commercial reduced-fat product enriched with linolenic and linoleic acids (group L) and a 20% casein diet as control group C. Cas and L gave each other 24 mg/day of PUFA n-3 being the ratio n-6/n-3 8.1/1 and 7.6/1, respectively. Thymus was removed and weighted and cell number were determined; blood was recollected and Total cholesterol, triacylglycerol, HDL and LDL-cholesterol fractions and myristic, palmitic, stearic, oleic, linoleic, linolenic, araquidonic, EPA and DHA fatty acid concentrations were measured in serum. Statistical analysis was performed using Anova test. Cell number were higher (p<0.01) in Cas (44.48+/-8.20) and in L (56.45+/-14.72) when compared to group D (1.80+/-0.70) and group C (23.70+/-4.04). L presented lower values of cholesterol, HDL and LDL-cholesterol (p<0.01) and higher values of triacylglycerol (p<0.05) when compared to Cas, being EPA (p<0.05) and DHA (p<0.01) higher in Cas. Being PUFA n-3 contribution the same in Cas and L, both diets were able to reverse the thymic athropy presenting a different hipolipemic behavior due to the different sources of PUFA n-3 used in the diets.
Mateos, Hintsa T; Lewandowski, Paul A; Su, Xiao Q
This study was conducted to investigate the effects of fish oil (FO) supplements on fatty acid composition and the expression of ∆6 desaturase and elongase 2 genes in Jade Tiger abalone. Five test diets were formulated to contain 0.5, 1.0, 1.5, 2.0 and 2.5% of FO respectively, and the control diet was the normal commercial abalone diet with no additional FO supplement. The muscle, gonad and digestive glands (DG) of abalone fed with all of the five test diets showed significantly high levels of total n-3 polyunsaturated fatty acid (PUFA), eicosapentaenoic acid (EPA), docosapentaenoic acid n-3 (DPAn-3), and docosahexaenoic acid (DHA) than the control group. In all three types of tissue, abalone fed diet supplemented with 1.5% FO showed the highest level of these fatty acids (P < 0.05). For DPAn-3 the higher level was also found in muscle and gonad of abalone fed diet supplemented with 2% FO (P < 0.05). Elongase 2 expression was markedly higher in the muscle of abalone fed diet supplemented with 1.5% FO (P < 0.05), followed by the diet containing 2% FO supplement. For ∆6 desaturase, significantly higher expression was observed in muscle of abalone fed with diet containing 0.5% FO supplement (P < 0.05). Supplementation with FO in the normal commercial diet can significantly improve long chain n-3 PUFA level in cultured abalone, with 1.5% being the most effective supplementation level.
Ney, Jacqueline G; Koury, Josely C; Azeredo, Vilma B; Casimiro-Lopes, Gustavo; Trugo, Nadia M F; Torres, Alexandre G
We hypothesize that membrane stability of elite swimmers adapted to chronic intense training is dependent on polyunsaturated fatty acids (PUFAs) and tocopherols in blood pools and that the composition of PUFA in plasma nonesterified fatty acids (NEFAs) might be associated with specific subcutaneous fat sites. Our aims were to investigate in male elite swimmers the associations of n-6 and n-3 PUFA and alpha- and gamma-tocopherols with proxies of membrane stability (phase angle and erythrocyte osmotic fragility) and of PUFA in plasma NEFA with specific skinfolds. Brazilian male elite swimmers (n = 20) under regular training for an average of 4.1 h/d and 6.1 d/wk took part in the study. Blood samples were obtained once after 18-hour rest and an overnight fast. Fatty acids were determined in plasma NEFA and erythrocytes by gas chromatolography and tocopherols were determined in plasma and erythrocytes by high-performance liquid chromatography. The status of PUFA was assessed as mean melting point, PUFA index [(Sigman-6 + Sigman-3) / (Sigman-7 + Sigman-9)] and docosahexaenoic acid indices (22:5n-6/22:4n-6 and 22:6n-3/22:5n-6 ratios) calculated from erythrocyte fatty acids. Phase angle was associated with an index of docosahexaenoic acid inadequacy (22:5n-6/22:4n-6; r = -0.53, P = .019) and with 22:5n-3 in erythrocytes (r = 0.51, P = .024), and erythrocyte osmotic fragility was associated with plasma alpha-tocopherol (r = -0.51, P = .05), which is a biomarker of vitamin E status. Plasma NEFAs 18:3n-3 and 20:4n-6 were positively associated with skinfolds of the trunk and arms (r = 0.49-0.59, P = .011-.043). The data presented indicate that n-3 PUFA and vitamin E states possibly improve membrane stability in elite swimmers and that the extent of specific anatomic sites of subcutaneous adipose tissue in the upper body might contribute to the composition of NEFA in the resting state.
Mbodji, Khaly; Charpentier, Cloé; Guérin, Charlène; Querec, Coraline; Bole-Feysot, Christine; Aziz, Moutaz; Savoye, Guillaume; Déchelotte, Pierre; Marion-Letellier, Rachel
5-aminosalicylic acid (5-ASA) is widely used for the treatment of inflammatory bowel disease (IBD). Recent studies have evaluated the potential of nutritional intervention as adjunct therapy to 5-ASA in IBD. N-3 polyunsaturated fatty acids (PUFA) have shown potent anti-inflammatory properties in gut inflammation. Therefore, we aimed to evaluate the efficacy of the dual therapy (n-3 PUFA plus 5-ASA) in rats with 2, 4, 6-trinitrobenzen sulfonic acid (TNBS)-induced colitis. Colitis was induced by intrarectal injection of TNBS while control rats received the vehicle. Rats received by gavage a fish oil-rich formula (n-3 groups) or an isocaloric and isolipidic oil formula supplemented with 5-ASA for 14 days. A dose response of 5-ASA (5-75 mg. suppression mg kg(-1) d(-1)) was tested. Colitis was evaluated and several inflammatory markers were quantified in the colon. COX-2 expression (P<.05) and pro-inflammatory eicosanoids production of prostaglandin E2 (P<.001) and leukotriene B4 (P<.001) were significantly inhibited by n-3 PUFA or 5-ASA therapy. 5-ASA also reduces mRNA levels of tumor necrosis factor α (P<.05). n-3 PUFA or 5-ASA significantly inhibits nuclear factor κB (NF-κB) activation (P<.01 and P<.05, respectively). The dual therapy n-3 PUFA plus 5-ASA also inhibited inflammatory response by lowering NF-κB activation (P<.01) or inducing peroxisome proliferator-activated receptor-γ (PPARγ) expression (P<.05). These results indicate that 5-ASA plus n-3 PUFAs are more effective than a higher dose of 5-ASA alone to reduce NF-κB activation and to induce PPARγ. By contrast, the dual therapy did not improve the effects of individual treatments on eicosanoids or cytokine production. Use of n-3 PUFA in addition to 5-ASA may reduce dose of standard therapy.
Forouhi, Nita G.; Schulze, Matthias B.; Zheng, Jusheng; Ye, Zheng; Kröger, Janine; Wang, Laura Yun; Summerhill, Keith; Griffin, Julian L.; Feskens, Edith J. M.; Affret, Aurélie; Amiano, Pilar; Boeing, Heiner; Dow, Courtney; Fagherazzi, Guy; Franks, Paul W.; Gonzalez, Carlos; Kaaks, Rudolf; Key, Timothy J.; Khaw, Kay Tee; Kühn, Tilman; Mortensen, Lotte Maxild; Nilsson, Peter M.; Overvad, Kim; Pala, Valeria; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Scalbert, Augustin; Slimani, Nadia; Spijkerman, Annemieke M. W.; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L.; Riboli, Elio
Background Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. Methods and Findings Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88–0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77–0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85–0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs. Conclusions These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they
Pegolo, Sara; Cecchinato, Alessio; Mach, Núria; Babbucci, Massimiliano; Pauletto, Marianna; Bargelloni, Luca; Schiavon, Stefano; Bittante, Giovanni
The aim of the present study was to identify transcriptional modifications and regulatory networks accounting for physiological and metabolic responses to specific nutrients in the liver of young Belgian Blue × Holstein bulls using RNA-sequencing. A larger trial has been carried out in which animals were fed with different diets: 1] a conventional diet; 2] a low-protein/low-mineral diet (low-impact diet) and 3] a diet enriched in n-3 fatty acids (FAs), conjugated linoleic acid (CLA) and vitamin E (nutraceutical diet). The initial hypothesis was that the administration of low-impact and nutraceutical diets might influence the transcriptional profiles in bovine liver and the resultant nutrient fluxes, which are essential for optimal liver function and nutrient interconversion. Results showed that the nutraceutical diet significantly reduced subcutaneous fat covering in vivo and liver pH. Dietary treatments did not affect overall liver fat content, but significantly modified the liver profile of 33 FA traits (out of the total 89 identified by gas-chromatography). In bulls fed nutraceutical diet, the percentage of n-3 and CLA FAs increased around 2.5-fold compared with the other diets, whereas the ratio of n6/n3 decreased 2.5-fold. Liver transcriptomic analyses revealed a total of 198 differentially expressed genes (DEGs) when comparing low-impact, nutraceutical and conventional diets, with the nutraceutical diet showing the greatest effects on liver transcriptome. Functional analyses using ClueGo and Ingenuity Pathway Analysis evidenced that DEGs in bovine liver were variously involved in energy reserve metabolic process, glutathione metabolism, and carbohydrate and lipid metabolism. Modifications in feeding strategies affected key transcription factors regulating the expression of several genes involved in fatty acid metabolism, e.g. insulin-induced gene 1, insulin receptor substrate 2, and RAR-related orphan receptor C. This study provides noteworthy insights into
Pegolo, Sara; Cecchinato, Alessio; Mach, Núria; Babbucci, Massimiliano; Pauletto, Marianna; Bargelloni, Luca; Schiavon, Stefano; Bittante, Giovanni
The aim of the present study was to identify transcriptional modifications and regulatory networks accounting for physiological and metabolic responses to specific nutrients in the liver of young Belgian Blue × Holstein bulls using RNA-sequencing. A larger trial has been carried out in which animals were fed with different diets: 1] a conventional diet; 2] a low-protein/low-mineral diet (low-impact diet) and 3] a diet enriched in n-3 fatty acids (FAs), conjugated linoleic acid (CLA) and vitamin E (nutraceutical diet). The initial hypothesis was that the administration of low-impact and nutraceutical diets might influence the transcriptional profiles in bovine liver and the resultant nutrient fluxes, which are essential for optimal liver function and nutrient interconversion. Results showed that the nutraceutical diet significantly reduced subcutaneous fat covering in vivo and liver pH. Dietary treatments did not affect overall liver fat content, but significantly modified the liver profile of 33 FA traits (out of the total 89 identified by gas-chromatography). In bulls fed nutraceutical diet, the percentage of n-3 and CLA FAs increased around 2.5-fold compared with the other diets, whereas the ratio of n6/n3 decreased 2.5-fold. Liver transcriptomic analyses revealed a total of 198 differentially expressed genes (DEGs) when comparing low-impact, nutraceutical and conventional diets, with the nutraceutical diet showing the greatest effects on liver transcriptome. Functional analyses using ClueGo and Ingenuity Pathway Analysis evidenced that DEGs in bovine liver were variously involved in energy reserve metabolic process, glutathione metabolism, and carbohydrate and lipid metabolism. Modifications in feeding strategies affected key transcription factors regulating the expression of several genes involved in fatty acid metabolism, e.g. insulin-induced gene 1, insulin receptor substrate 2, and RAR-related orphan receptor C. This study provides noteworthy insights into
Neijat, M; Suh, M; Neufeld, J; House, J D
Hempseed products represent potential alternative feed ingredients for poultry. However, their usage is not currently approved due to a lack of data to support their safety and efficacy. In this regard, the current study was conducted to assess the impact of dietary concentration of hempseed (HS) products and duration of their feeding to hens on the polyunsaturated fatty acid (PUFA) composition of egg yolk lipids. In the current study, 48 Lohmann LSL-Classic hens were individually housed in metabolism cages, in a completely randomized design, and provided one of six diets (wheat-barley-soybean-based) containing either HS (10, 20 and 30 %), hempseed oil (HO; 4.5 and 9.0 %) or no hempseed product (control) over 12 weeks. Increasing alpha-linolenic acid (ALA) intake via increasing dietary hempseed product inclusion, significantly (p < 0.0001) increased the n-3 PUFA contents of yolk total lipid. The values of ALA increased by 12-fold (152 ± 3.56 and 156 ± 2.42 mg/yolk) and docosahexaenoic acid (DHA) by twofold to threefold (41.3 ± 1.57 and 43.6 ± 1.61 mg/yolk) over the control, for the highest levels of HS and HO inclusion, respectively. Increasing levels of hemp products in laying hen diets proved effective in manipulating the fatty acid profile of the total lipid, triacylglycerol (TAG) and total phospholipid (PL) fractions of yolks, enhancing the n-3 fatty acids and reducing the n-6/n-3 ratio. The latter benefit was achieved within 4 weeks of feeding hens either HS- or HO-containing diets.
Mingam, Rozenn; Moranis, Aurélie; Bluthé, Rose-Marie; De Smedt-Peyrusse, Véronique; Kelley, Keith W.; Guesnet, Philippe; Lavialle, Monique; Dantzer, Robert; Layé, Sophie
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
Miles, Elizabeth A; Calder, Philip C
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (ARA) is the precursor of inflammatory eicosanoids which are involved in RA. Some therapies used in RA target ARA metabolism. Marine n-3 PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) found in oily fish and fish oils decrease the ARA content of cells involved in immune responses and decrease the production of inflammatory eicosanoids from ARA. EPA gives rise to eicosanoid mediators that are less inflammatory than those produced from ARA and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving, although little is known about these latter mediators in RA. Marine n-3 PUFAs can affect other aspects of immunity and inflammation relevant to RA, including dendritic cell and T cell function and production of inflammatory cytokines and reactive oxygen species, although findings for these outcomes are not consistent. Fish oil has been shown to slow the development of arthritis in animal models and to reduce disease severity. A number of randomised controlled trials of marine n-3 PUFAs have been performed in patients with RA. A systematic review included 23 studies. Evidence is seen for a fairly consistent, but modest, benefit of marine n-3 PUFAs on joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity, and use of non-steroidal anti-inflammatory drugs.
Sublette, M Elizabeth; Segal-Isaacson, C J; Cooper, Thomas B; Fekri, Shiva; Vanegas, Nora; Galfalvy, Hanga C; Oquendo, Maria A; Mann, J John
The role of n-3 polyunsaturated fatty acids (PUFAs) in psychiatric illness is a topic of public health importance. This report describes development and biomarker validation of a 21-item, self-report food frequency questionnaire (FFQ) intended for use in psychiatric research to assess intake of α-linolenic acid (18:3n-3 [ALA]), docosahexaenoic acid (22:6n-3 [DHA]), and eicosapentaenoic acid (20:5n-3 [EPA]). In a cross-sectional study conducted from September 2006 to September 2008, sixty-one ethnically diverse adult participants with (n=34) and without (n=27) major depressive disorder completed this n-3 PUFA FFQ and provided a plasma sample. Plasma levels of n-3 PUFAs EPA and DHA, and n-6 PUFA arachidonic acid (20:4n-6 [AA]) were quantified by gas chromatography. Using Spearman's ρ, FFQ-estimated intake correlated with plasma levels of DHA (r=0.50; P<0.0001) and EPA (r=0.38; P=0.002), but not with ALA levels (r=0.22; P=0.086). Participants were classified into quartiles by FFQ-estimated intake and plasma PUFA concentrations. Efficacy of the FFQ to rank individuals into same or adjacent plasma quartiles was 83% for DHA, 78.1% for EPA, and 70.6% for ALA; misclassification into extreme quartiles was 4.9% for DHA, 6.5% for EPA, and 8.2% for ALA. FFQ-estimated EPA intake and plasma EPA were superior to plasma AA levels as predictors of the plasma AA to EPA ratio. This brief FFQ can provide researchers and clinicians with valuable information concerning dietary intake of DHA and EPA.
Sanders, Thomas A B
Plants provide α-linolenic acid [ALA; 18:3n-3 (18:3ω-3)], which can be converted via eicosapentaenoic acid (EPA; 20:5n-3) to docosahexaenoic acid (DHA; 22:6n-3), which is required for normal visual and cognitive function. Dietary ALA is provided mainly by vegetable oils, especially soybean and rapeseed oils, but is destroyed by partial hydrogenation; it is also present in high amounts in walnuts and flaxseed. Dietary EPA and DHA are provided mainly by fish and so are absent from vegan diets and only present in trace amounts in vegetarian diets. Vegetarians and vegans have lower proportions of DHA in blood and tissue lipids compared with omnivores. High intakes of EPA and DHA (typically in the range of 3-5 g/d) but not ALA have favorable effects on several cardiovascular disease (CVD) risk factors and have been postulated to delay arterial aging and cardiovascular mortality, but these intakes are beyond the range of normal dietary intake. Arterial stiffness, which is a measure of arterial aging, appears to be lower in vegans than in omnivores; and risk of CVD in vegetarians and vegans is approximately one-third that in omnivores. Prospective cohort studies showed higher intakes of EPA+DHA, and less consistently ALA, to be associated with a lower risk of CVD, especially fatal coronary heart disease, but meta-analyses of randomized controlled trials of supplementation of EPA+DHA or ALA in secondary prevention of CVD showed no clear benefit. Current evidence is insufficient to warrant advising vegans and vegetarians to supplement their diets with EPA or DHA for CVD prevention.
Houthuijzen, Julia M.; Oosterom, Ilse; Hudson, Brian D.; Hirasawa, Akira; Daenen, Laura G. M.; McLean, Chelsea M.; Hansen, Steffen V. F.; van Jaarsveld, Marijn T. M.; Peeper, Daniel S.; Jafari Sadatmand, Sahar; Roodhart, Jeanine M. L.; van de Lest, Chris H. A.; Ulven, Trond; Ishihara, Kenji; Milligan, Graeme; Voest, Emile E.
Although chemotherapy is designed to eradicate tumor cells, it also has significant effects on normal tissues. The platinum-induced fatty acid 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid) induces systemic resistance to a broad range of DNA-damaging chemotherapeutics. We show that 16:4(n-3) exerts its effect by activating splenic F4/80+/CD11blow macrophages, which results in production of chemoprotective lysophosphatidylcholines (LPCs). Pharmacologic studies, together with analysis of expression patterns, identified GPR120 on F4/80+/CD11blow macrophages as the relevant receptor for 16:4(n-3). Studies that used splenocytes from GPR120-deficient mice have confirmed this conclusion. Activation of the 16:4(n-3)-GPR120 axis led to enhanced cPLA2 activity in these splenic macrophages and secretion of the resistance-inducing lipid mediator, lysophosphatidylcholine(24:1). These studies identify a novel and unexpected function for GPR120 and suggest that antagonists of this receptor might be effective agents to limit development of chemotherapy resistance.—Houthuijzen, J. M., Oosterom, I., Hudson, B. D., Hirasawa, A., Daenen, L. G. M., McLean, C. M., Hansen, S. V. F., van Jaarsveld, M. T. M., Peeper, D. S., Jafari Sadatmand, S., Roodhart, J. M. L., van de Lest, C. H. A., Ulven, T., Ishihara, K., Milligan, G., Voest, E. E. Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance.
Tsai, Alexander C; Lucas, Michel; Okereke, Olivia I; O'Reilly, Eilis J; Mirzaei, Fariba; Kawachi, Ichiro; Ascherio, Alberto; Willett, Walter C
Intake of n-3 and n-6 polyunsaturated fatty acids (PUFAs) has been implicated in the pathogenesis of depression. We sought to estimate the association between intake of fish and n-3 and n-6 PUFAs and suicide mortality over the course of long-term follow-up. In this prospective cohort study, biennial questionnaires were administered to 42,290 men enrolled in the Health Professionals Follow-up Study (1988-2008), 72,231 women enrolled in the Nurses' Health Study (1986-2008), and 90,836 women enrolled in Nurses' Health Study II (1993-2007). Dietary fish and n-3 and n-6 PUFA intakes were assessed every 4 years using a validated food-frequency questionnaire. Suicide mortality was ascertained through blind physician review of death certificates and hospital or pathology reports. Adjusted relative risks of suicide mortality were estimated with multivariable Cox proportional hazards models and pooled across cohorts using random-effects meta-analysis. The pooled multivariable relative risks for suicide among persons in the highest quartile of intake of n-3 or n-6 PUFAs, relative to the lowest quartile, ranged from 1.08 to 1.46 for n-3 PUFAs (Ptrend = 0.11-0.52) and from 0.68 to 1.19 for n-6 PUFAs (Ptrend = 0.09-0.54). We did not find evidence that intake of n-3 PUFAs or fish lowered the risk of completed suicide.
Wood, K E; Lau, A; Mantzioris, E; Gibson, R A; Ramsden, C E; Muhlhausler, B S
This study aimed to determine the effect of reducing the dietary linoleic acid (LA) intake from ~5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks. Nutrient intakes were estimated from diet diaries and blood samples were collected for assessment of fatty acid composition in plasma and erythrocyte phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA intervention (P<0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were significantly reduced after the low LA diet phase (P<0.001). The n-3 LCPUFA content of plasma phospholipids was significantly increased after the low LA diet compared to baseline (6.22% vs. 5.53%, P<0.001). These data demonstrate that reducing LA intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake.
Marze, Sébastien; Meynier, Anne; Anton, Marc
The in vitro digestion of β-lactoglobulin stabilized emulsions rich in the n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), was studied using several physicochemical techniques. Artificial media for the mouth, stomach and small intestine were used in a sequential static in vitro digestion method. Different sizing techniques were compared to follow the droplet size during the digestion steps, including diffusing wave spectroscopy (DWS) which allowed direct measurements on undiluted emulsions. Titration of fatty acids confirmed that the digestion of such emulsified fish oils is partial. The study of the digestion at the oil-water interface using tensiometry revealed specific affinities between lipids and proteins. These could explain the emulsion and the single droplet lipolysis. Nevertheless, by comparing our results to a previous study on fish oil lipolysis, we identified two other important factors. Those were the aqueous solubility and the rate of hydrolysis of the individual fatty acids, the emulsion with the most soluble and hydrolysable ones being digested more quickly.
Hichami, A.; Grissa, O.; Mrizak, I.; Benammar, C.; Khan, N. A.
Th (T helper) cells are differentiated into either Th1 or Th2 phenotype. It is generally considered that Th1 phenotype is proinflammatory, whereas Th2 phenotype exerts anti-inflammatory or protective effects. Gestational diabetes mellitus (GDM) has been associated with a decreased Th1 phenotype, whereas macrosomia is marked with high expression of Th1 cytokines. Besides, these two pathological situations are marked with high concentrations of inflammatory mediators like tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), known to play a pivotal role in insulin resistance. Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) may exert a beneficial effect by shifting Th1/Th2 balance to a Th2 phenotype and increasing insulin sensitivity. In this paper, we shed light on the role of T-cell malfunction that leads to an inflammatory and pathophysiological state, related to insulin resistance in GDM and macrosomia. We will also discuss the nutritional management of these pathologies by dietary n-3 polyunsaturated fatty acids (PUFAs). PMID:27313878
Pipingas, Andrew; Cockerell, Robyn; Grima, Natalie; Sinclair, Andrew; Stough, Con; Scholey, Andrew; Myers, Stephen; Croft, Kevin; Sali, Avni; Pase, Matthew P
The present randomized, placebo-controlled, double-blind, parallel-groups clinical trial examined the effects of fish oil and multivitamin supplementation on the incorporation of n-3 and n-6 fatty acids into red blood cells. Healthy adult humans (n = 160) were randomized to receive 6 g of fish oil, 6 g of fish oil plus a multivitamin, 3 g of fish oil plus a multivitamin or a placebo daily for 16 weeks. Treatment with 6 g of fish oil, with or without a daily multivitamin, led to higher eicosapentaenoic acid (EPA) composition at endpoint. Docosahexaenoic acid (DHA) composition was unchanged following treatment. The long chain LC n-3 PUFA index was only higher, compared to placebo, in the group receiving the combination of 6 g of fish oil and the multivitamin. Analysis by gender revealed that all treatments increased EPA incorporation in females while, in males, EPA was only significantly increased by the 6 g fish oil multivitamin combination. There was considerable individual variability in the red blood cell incorporation of EPA and DHA at endpoint. Gender contributed to a large proportion of this variability with females generally showing higher LC n-3 PUFA composition at endpoint. In conclusion, the incorporation of LC n-3 PUFA into red blood cells was influenced by dosage, the concurrent intake of vitamin/minerals and gender.
Orchard, Tonya S.; Ing, Steven W.; Lu, Bo; Belury, Martha A.; Johnson, Karen; Wactawski-Wende, Jean; Jackson, Rebecca D.
Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) in red blood cells (RBC) are an objective indicator of PUFA status and may be related to hip fracture risk. The primary objective of this study was to examine RBC PUFAs as predictors of hip fracture risk in postmenopausal women. A nested case-control study (n=400 pairs) was completed within the Women’s Health Initiative (WHI) using 201 incident hip fracture cases from the Bone Mineral Density (BMD) cohort, along with 199 additional incident hip fracture cases randomly selected from the WHI Observational Study. Cases were 1:1 matched on age, race, and hormone use with non-hip fracture controls. Stored baseline RBCs were analyzed for fatty acids using gas chromatography. After removing degraded samples, 324 matched pairs were included in statistical analyses. Stratified Cox proportional hazard models were constructed according to case-control pair status; risk of fracture was estimated for tertiles of RBC PUFA. In adjusted hazard models, lower hip fracture risk was associated with higher RBC α-linolenic acid [Hazard ratio (HR) Tertile 3 (T3): 0.44; 95% CI: 0.23-0.85; p for linear trend 0.0154)], eicosapentaenoic acid (HR T3: 0.46; 95% CI: 0.24-0.87; p for linear trend 0.0181) and total n-3 PUFAs (HR T3: 0.55; 95% CI: 0.30-1.01; p for linear trend 0.0492). Conversely, hip fracture nearly doubled with the highest RBC n-6/n-3 ratio (HR T3: 1.96; 95% CI: 1.03-3.70; p for linear trend 0.0399). RBC PUFAs were not associated with BMD. RBC PUFAs were indicative of dietary intake of marine n-3 PUFAs (Spearman’s rho=0.45, p<0.0001), total n-6 PUFAs (rho=0.17, p<0.0001) and linoleic acid (rho= 0.09, p<0.05). These results suggest that higher RBC α-linolenic acid, as well as eicosapentaenoic acid and total n-3 PUFAs, may predict lower hip fracture risk. Contrastingly, a higher RBC n-6/n-3 ratio may predict higher hip fracture risk in postmenopausal women. PMID:23018646
McAnulty, Steven R; Nieman, David C; McAnulty, Lisa S; Lynch, Worley S; Jin, Fuxia; Henson, Dru A
Consumption of plant flavonoids, antioxidants, and n-3 fatty acids is proposed to have many potential health benefits derived primarily through antioxidant and anti-inflammatory activities. This study examined the effects of 1,000 mg quercetin + 1,000 mg vitamin C (QC); 1,000 mg quercetin, 1,000 mg vitamin C, 400 mg isoquercetin, 30 mg epigallocatechin gallate, and 400 mg n-3 fatty acids (QFO); or placebo (P), taken each day for 2 wk before and during 3 d of cycling at 57% W(max) for 3 hr, on plasma antioxidant capacity (ferricreducing ability of plasma [FRAP], oxygen-radical absorbance capacity [ORAC]), plasma oxidative stress (F(2)-isoprostanes), and plasma quercetin and vitamin C levels. Thirty-nine athletes were recruited and randomized to QC, QFO, or P. Blood was collected at baseline, after 2 wk supplementation, immediately postexercise, and 14 hr postexercise. Statistical design used a 3 (groups) × 4 (times) repeated-measures ANOVA with post hoc analyses. Plasma quercetin was significantly elevated in QC and QFO compared with P. Plasma F(2)-isoprostanes, FRAP, and vitamin C were significantly elevated and ORAC significantly decreased immediately postexercise, but no difference was noted in the overall pattern of change. Post hoc analyses revealed that the QC and QFO groups did not exhibit a significant increase in F(2)-isoprostanes from baseline to immediately postexercise compared with P. This study indicates that combining flavonoids and antioxidants with n-3 fatty acids is effective in reducing the immediate postexercise increase in F(2)-isoprostanes. Moreover, this effect occurs independently of changes in plasma antioxidant capacity.
Batetta, Barbara; Griinari, Mikko; Carta, Gianfranca; Murru, Elisabetta; Ligresti, Alessia; Cordeddu, Lina; Giordano, Elena; Sanna, Francesca; Bisogno, Tiziana; Uda, Sabrina; Collu, Maria; Bruheim, Inge; Di Marzo, Vincenzo; Banni, Sebastiano
Dietary (n-3) long-chain PUFA [(n-3) LCPUFA] ameliorate several metabolic risk factors for cardiovascular diseases, although the mechanisms of these beneficial effects are not fully understood. In this study, we compared the effects of dietary (n-3) LCPUFA, in the form of either fish oil (FO) or krill oil (KO) balanced for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content, with a control (C) diet containing no EPA and DHA and similar contents of oleic, linoleic, and alpha-linolenic acids, on ectopic fat and inflammation in Zucker rats, a model of obesity and related metabolic dysfunction. Diets were fed for 4 wk. Given the emerging evidence for an association between elevated endocannabinoid concentrations and metabolic syndrome, we also measured tissue endocannabinoid concentrations. In (n-3) LCPUFA-supplemented rats, liver triglycerides and the peritoneal macrophage response to an inflammatory stimulus were significantly lower than in rats fed the control diet, and heart triglycerides were lower, but only in KO-fed rats. These effects were associated with a lower concentration of the endocannabinoids, anandamide and 2-arachidonoylglycerol, in the visceral adipose tissue and of anandamide in the liver and heart, which, in turn, was associated with lower levels of arachidonic acid in membrane phospholipids, but not with higher activity of endocannabinoid-degrading enzymes. Our data suggest that the beneficial effects of a diet enriched with (n-3) LCPUFA are the result of changes in membrane fatty acid composition. The reduction of substrates for inflammatory molecules and endocannabinoids may account for the dampened inflammatory response and the physiological reequilibration of body fat deposition in obese rats.
Bo, Yacong; Zhang, Xueyuan; Wang, Youli; You, Jie; Cui, Han; Zhu, Yiwei; Pang, Wei; Liu, Wei; Jiang, Yugang; Lu, Quanjun
Objective: Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against mild cognitive impairment (MCI). However, there is still a lack of the n-3 PUFAs intervention in the elderly with MCI in China. The aim of the present study was to investigate the effect of n-3 PUFA supplementation on cognitive function in the Chinese elderly with MCI. Methods: Eighty six MCI individuals aged 60 years or older were randomly assigned to receive either n-3 PUFAs (480 mg DHA and 720 mg EPA per day, n = 44) or placebo (olive oil, n = 42) capsules. The changes of cognitive functions were assessed using Basic Cognitive Aptitude Tests (BCAT). Results: The mean age of participants was 71 years old, and 59% of the participants were men. n-3 PUFA supplementation was associated with improved total BCAT scores, perceptual speed, space imagery efficiency, and working memory (p < 0.01), but not with mental arithmetic efficiency or recognition memory (p > 0.05). Subgroup analysis by sex showed that n-3 PUFAs significantly improved perceptual speed (p = 0.001), space imagery efficiency (p = 0.013), working memory (p = 0.018), and total BCAT scores (p = 0.000) in males. However, in females, the significant beneficial effects can only be observed in perceptual speed (p = 0.027), space imagery efficiency (p = 0.006), and total BCAT scores (p = 0.015)—not working memory (p = 0.113). Conclusion: n-3 PUFAs can improve cognitive function in people with MCI. Further studies with different fish oil dosages, longer intervention periods, and larger sample sizes should be investigated before definite recommendations can be made. PMID:28075381
Tremblay, André J; Lamarche, Benoît; Hogue, Jean-Charles; Couture, Patrick
Dietary n-3 polyunsaturated fatty acids (PUFAs) have been proposed to modulate plasma lipids, lipoprotein metabolism, and inflammatory state and to reduce triglyceride (TG) concentrations. The present double-blind, randomized, placebo-controlled, crossover study investigated the effects of n-3 PUFA supplementation at 3 g/d for 8 weeks on the intravascular kinetics of intestinally derived apolipoprotein (apo) B-48-containing lipoproteins in 10 men with type 2 diabetes. In vivo kinetics of the TG-rich lipoprotein (TRL) apoB-48 and VLDL apoB-100 were assessed using a primed-constant infusion of L-[5,5,5-D3] leucine for 12 hours in a fed state. Compared with the placebo, n-3 PUFA supplementation significantly reduced fasting TG concentrations by -9.7% (P = 0.05) but also significantly increased plasma levels of cholesterol (C) (+6.0%, P = 0.05), LDL-C (+12.2%, P = 0.04), and HDL-C (+8.4, P = 0.007). n-3 PUFA supplementation had no significant impact on postprandial TRL apoB-48 and VLDL apoB-100 levels or on the production or catabolic rates of these lipoproteins. These data indicate that 8-week supplementation with n-3 PUFAs in men with type 2 diabetes has no beneficial effect on TRL apoB-48 and VLDL apoB-100 levels or kinetics.
Mazahery, Hajar; Stonehouse, Welma; Delshad, Maryam; Kruger, Marlena C.; Conlon, Cathryn A.; Beck, Kathryn L.; von Hurst, Pamela R.
Omega-3 long chain polyunsaturated fatty acid supplementation (n-3 LCPUFA) for treatment of Autism Spectrum Disorder (ASD) is popular. The results of previous systematic reviews and meta-analyses of n-3 LCPUFA supplementation on ASD outcomes were inconclusive. Two meta-analyses were conducted; meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of n-3 LCPUFA supplementation to placebo on symptoms of ASD. Case-control studies and randomised controlled trials (RCTs) were identified searching electronic databases up to May, 2016. Mean differences were pooled and analysed using inverse variance models. Heterogeneity was assessed using I2 statistic. Fifteen case-control studies (n = 1193) were reviewed. Compared with typically developed, ASD populations had lower DHA (−2.14 [95% CI −3.22 to −1.07]; p < 0.0001; I2 = 97%), EPA (−0.72 [95% CI −1.25 to −0.18]; p = 0.008; I2 = 88%), and ARA (−0.83 [95% CI, −1.48 to −0.17]; p = 0.01; I2 = 96%) and higher total n-6 LCPUFA to n-3 LCPUFA ratio (0.42 [95% CI 0.06 to 0.78]; p = 0.02; I2 = 74%). Four RCTs were included in meta-analysis 2 (n = 107). Compared with placebo, n-3 LCPUFA improved social interaction (−1.96 [95% CI −3.5 to −0.34]; p = 0.02; I2 = 0) and repetitive and restricted interests and behaviours (−1.08 [95% CI −2.17 to −0.01]; p = 0.05; I2 = 0). Populations with ASD have lower n-3 LCPUFA status and n-3 LCPUFA supplementation can potentially improve some ASD symptoms. Further research with large sample size and adequate study duration is warranted to confirm the efficacy of n-3 LCPUFA. PMID:28218722
Mazahery, Hajar; Stonehouse, Welma; Delshad, Maryam; Kruger, Marlena C; Conlon, Cathryn A; Beck, Kathryn L; von Hurst, Pamela R
Omega-3 long chain polyunsaturated fatty acid supplementation (n-3 LCPUFA) for treatment of Autism Spectrum Disorder (ASD) is popular. The results of previous systematic reviews and meta-analyses of n-3 LCPUFA supplementation on ASD outcomes were inconclusive. Two meta-analyses were conducted; meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of n-3 LCPUFA supplementation to placebo on symptoms of ASD. Case-control studies and randomised controlled trials (RCTs) were identified searching electronic databases up to May, 2016. Mean differences were pooled and analysed using inverse variance models. Heterogeneity was assessed using I² statistic. Fifteen case-control studies (n = 1193) were reviewed. Compared with typically developed, ASD populations had lower DHA (-2.14 [95% CI -3.22 to -1.07]; p < 0.0001; I² = 97%), EPA (-0.72 [95% CI -1.25 to -0.18]; p = 0.008; I² = 88%), and ARA (-0.83 [95% CI, -1.48 to -0.17]; p = 0.01; I² = 96%) and higher total n-6 LCPUFA to n-3 LCPUFA ratio (0.42 [95% CI 0.06 to 0.78]; p = 0.02; I² = 74%). Four RCTs were included in meta-analysis 2 (n = 107). Compared with placebo, n-3 LCPUFA improved social interaction (-1.96 [95% CI -3.5 to -0.34]; p = 0.02; I² = 0) and repetitive and restricted interests and behaviours (-1.08 [95% CI -2.17 to -0.01]; p = 0.05; I² = 0). Populations with ASD have lower n-3 LCPUFA status and n-3 LCPUFA supplementation can potentially improve some ASD symptoms. Further research with large sample size and adequate study duration is warranted to confirm the efficacy of n-3 LCPUFA.
Mizia-Stec, Katarzyna; Haberka, Maciej; Mizia, Magdalena; Chmiel, Artur; Gieszczyk, Klaudia; Lasota, Bartosz; Janowska, Joanna; Zahorska-Markiewicz, Barbara; Gąsior, Zbigniew
Introduction N-3 Polyunsaturated fatty acids (n-3 PUFA) exert clinical beneficial effects in patients after acute myocardial infarction (AMI). However, their exact mechanisms of action are not well recognized yet. Our aim was to evaluate effects of early introduced n-3 PUFA supplementation on endothelial function and serum adipokine concentrations in patients with AMI. Material and methods Thirty-eight patients with AMI and successful coronary stent implantation were randomized to the study group (PUFA group: n = 19; standard therapy + PUFA 1 g daily) and the control group (control group: n = 19; standard therapy). The study group patients were given n-3 PUFA (Omacor 1 g daily) starting from the 3rd day of AMI. Ultrasound vascular indexes (flow-mediated dilatation [FMD], nitroglycerine-mediated dilation [NMD]) and serum concentrations of adiponectin and resistin (ELISA) were evaluated before and after 30 days of pharmacotherapy. Results Comparison of the mean delta values (baseline/after 30 days of therapy) between groups revealed significant differences for delta FMD (PUFA 7.6 ±12.4% vs. control –1.7 ±10.5%, p = 0.019) and delta resistin concentrations (PUFA 1.0 ±3.8pg/ml vs. control –1.6 ±2.9pg/ml, p = 0.028). Multiple linear regression analysis for all subjects revealed the n-3 PUFA supplementation (r = 10.933, p = 0.004) and waist circumference (r = –0.467, p = 0.01) as independent factors associated with delta FMD values (R-adjusted 0.29; p = 0.002). Conclusions Early and short-term n-3 PUFA supplementation in AMI with successful primary PCI and optimal pharmacotherapy improves endothelial function. However, increased resistin serum levels observed after 1-month n-3 PUFA supplementation merits further investigations. PMID:22291823
Mohammed, Altaf; Janakiram, Naveena B; Brewer, Misty; Duff, Ashley; Lightfoot, Stan; Brush, Richard S; Anderson, Robert E; Rao, Chinthalapally V
Preclinical studies suggest that diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for prevention of pancreatic cancer. Nutritional intervention studies are often complex, and there is no clear evidence, without potential confounding factors, on whether conversion of n-6 PUFAs to n-3 PUFAs in pancreatic tissues would provide protection. Experiments were designed using n-3 fatty acid desaturase (Fat-1) transgenic mice, which can convert n-6 PUFA to n-3 FAs endogenously, to determine the impact of n-3 PUFAs on pancreatic intraepithelial neoplasms (PanINs) and their progression to pancreatic ductal adenocarcinoma (PDAC). Six-weekold female p48Cre/+-LSL-KrasG12D/+ andcompoundFat-1-p48Cre/+-LSL-KrasG12D/+ mice were fed (AIN-76A) diets containing 10% safflower oil for 35 weeks. Pancreata were evaluated histopathologically for PanINs and PDAC. Results showed a dramatic reduction in incidence of PDAC (84%; P < .02) in Fat-1-p48Cre/+-LSL-KrasG12D/+ mice compared to p48Cre/+-LSL-KrasG12D/+ mice. Importantly, significant reductions of pancreatic ducts with carcinoma (90%; P < .0001) and PanIN 3 (∼50%; P < .001) lesions were observed in the compound transgenic mice. The levels of n-3 PUFA were much higher (>85%; P < .05–0.01) in pancreas of compound transgenic mice than in those of p48Cre/+-LSL-KrasG12D/+ mice. Molecular analysis of the pancreas showed a significant down-regulation of proliferating cell nuclear antigen, cyclooxygenase-2, 5-lipoxygenase (5-LOX), 5-LOX-activating protein, Bcl-2, and cyclin D1 expression levels in Fat-1-p48Cre/+-LSL-KrasG12D/+ mice compared to p48Cre/+-LSL-KrasG12D/+ mice. These data highlight the promise of dietary n-3 FAs for chemoprevention of pancreatic cancer in high-risk individuals. PMID:23308056
Aoki, Aya; Inoue, Maiko; Nguyen, Elizabeth; Obata, Ryo; Kadonosono, Kazuaki; Shinkai, Shoji; Hashimoto, Hideki; Sasaki, Satoshi; Yanagi, Yasuo
This case-control study reports the association between nutrient intake and neovascular age-related macular degeneration (AMD) in Japan. The nutrient intake of 161 neovascular AMD cases from two university hospitals and 369 population-based control subjects from a cohort study was assessed using a brief-type self-administered questionnaire on diet history, which required respondent recall of the usual intake of 58 foods during the preceding month. Energy-adjusted nutrient intake values were compared between the groups. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% CIs adjusted for smoking history, age, sex, chronic disease history, supplement use, and alcohol consumption. Logistic regression analysis demonstrated that low intakes of n-3 fatty acid, α-tocopherol, zinc, vitamin D, vitamin C, and β-carotene were associated with neovascular AMD (Trend P < 0.0001 for n-3 fatty acid, Trend P < 0.0001 for α-tocopherol, Trend P < 0.0001 for zinc, Trend P = 0.002 for vitamin D, Trend P = 0.04 for vitamin C, Trend P = 0.0004 for β-carotene). There was no association with retinol or cryptoxanthin intake and neovascular AMD (P = 0.67, 0.06).
Munekata, P E S; Domínguez, R; Franco, D; Bermúdez, R; Trindade, M A; Lorenzo, Jose M
The effect of natural antioxidants on physicochemical properties, lipid and protein oxidation, volatile compounds and free fatty acids (FFA) were determined in Spanish salchichón enriched with n-3 fatty acids encapsulated and stabilized in konjac matrix. Phenolic compounds of beer residue extract (BRE), chestnut leaves extract (CLE) and peanut skin extract (PSE) were also identified and quantified. Five batches of salchichón were prepared: control (CON, without antioxidants), butylated hydroxytoluene (BHT), BRE, CLE and PSE. The main phenolic compounds were catechin and benzoic acid for BRE, gallic acid and catechin for CLE and catechin and protocatechuic acid for PSE. Statistical analysis did not show significant differences on chemical composition among treatments. Reductions in luminosity (P<0.05) and pH (P<0.001) were observed with the CLE batch, whereas the other colour parameters were not affected by the addition of natural antioxidants. Finally, the inclusion of antioxidants (P<0.001) decreased the hexanal content, whereas the FFA content increased by the addition of natural extracts.
Chiu, Cheng-Ying; Smyl, Christopher; Dogan, Inci; Rothe, Michael; Weylandt, Karsten-H.
Polyunsaturated fatty acids (PUFA) are precursors of bioactive metabolites and mediators. In this study, the profile of hydroxyeicosatetraenoic (HETE), hydroxyeicosapentaenoic (HEPE) and hydroxydocosahexaenoic (HDHA) acids derived from arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in colon, liver, lung, spleen, muscle, heart and kidney tissue of healthy wildtype mice were characterized, and compared to profiles in organs from transgenic fat-1 mice engineered to express the Caenorhabditis elegans fat-1 gene encoding an n-3 desaturase and thereby with endogenously elevated n-3 PUFA levels. PUFAs were measured using gas chromatography. The lipid metabolites were assayed using LC-MS/MS. AA and DHA were the prominent PUFAs in wildtype and fat-1 mice. EPA levels were low in both groups even though there was a significant increase in fat-1 organs with an up to 12-fold increase in fat-1 spleen and kidney. DHA levels increased by approximately 1.5-fold in fat-1 as compared to wildtype mice. While HETEs remained the same or decreased moderately and HDHAs increased 1- to 3-fold, HEPE formation in fat-1 tissues increased from 8- (muscle) to 44-fold (spleen). These findings indicate distinct profiles of monohydroxy lipid metabolites in different organs and strong utilization of EPA for HEPE formation, by which moderate EPA supplementation might trigger formation of biologically active EPA-derived resolvins. PMID:28165385
Hu, Yao; Li, Huaixing; Lu, Ling; Manichaikul, Ani; Zhu, Jingwen; Chen, Yii-Der I; Sun, Liang; Liang, Shuang; Siscovick, David S; Steffen, Lyn M; Tsai, Michael Y; Rich, Stephen S; Lemaitre, Rozenn N; Lin, Xu
Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci (MYB, AGPAT4, DGAT2 and PPT2) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor) ≥ 6). Of them, associations of MYB and AGPAT4 with docosatetraenoic acid (log10(Bayes Factor) = 11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses (P = 4.15 × 10(-14) and 4.30 × 10(-12), respectively), while associations of DGAT2 with gamma-linolenic acid (log10(Bayes Factor) = 6.16) and of PPT2 with docosapentaenoic acid (log10(Bayes Factor) = 6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses (P ≤ 0.003). We also confirmed previously reported loci including FADS1, NTAN1, NRBF2, ELOVL2 and GCKR. Different effect sizes in FADS1 and independent association signals in ELOVL2 were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations.
Baeza, E; Chartrin, P; Lessire, M; Meteau, K; Chesneau, G; Guillevic, M; Mourot, J
The aim of this study was to increase the content of n-3 fatty acids (FA) of meat without affecting its sensory and/or technological properties or the growth performance of chickens reared under standard conditions. Male chickens, Ross 308, were distributed into 5 groups corresponding to 5 different diets for the growing and finishing periods: control (T), containing extruded linseeds exhibiting high concentration of fibre (ELHF), extruded linseeds exhibiting low concentration of fibre (ELLF), microalgae, or an association of 75% ELLF and 25% MA (ELLF+MA). The diet containing microalgae induced a decrease in feed consumption without affecting growth rate. Chickens exhibited a lower feed conversion ratio than the other groups for the growing and finishing periods but also the whole rearing period. The use of linseeds in diets had no effect on the growth performance of chickens in comparison to the control group. The dietary enrichment with n-3 FA had few effects on carcass composition or the ultimate pH and colour of breast meat. The microalgae increased the meat susceptibility to oxidation. The lipid content of breast meat was not affected by the diets. The breast meat of chickens fed on diets containing linseeds and/or microalgae had greater n-3 FA content (2.4 to 3.9 times higher than group T). The linseeds and microalgae mainly increased the contents in linolenic acid and long chain n-3 FA, respectively. Dietary enrichment with n-3 FA had no effect on the sensory quality of fillets whereas the thighs of the MA group exhibited the lowest score for the flavour "chicken" and the greatest score for the flavour "abnormal" corresponding to a fish flavour.
Donahue, S M A; Rifas-Shiman, S L; Olsen, S F; Gold, D R; Gillman, M W; Oken, E
Maternal n-3 and n-6 polyunsaturated fatty acid (PUFA) status may influence birth outcomes and child health. We assessed second trimester maternal diet with food frequency questionnaires (FFQs) (n=1666), mid-pregnancy maternal erythrocyte PUFA concentrations (n=1550), and umbilical cord plasma PUFA concentrations (n=449). Mean (SD) maternal intake of total n-3 PUFA was 1.17 g/d (0.43), docosahexaenoic and eicosapentaenoic acids (DHA+EPA) 0.16 g/d (0.17), and total n-6 PUFA 12.25 g/d (3.25). Mean maternal erythrocyte and cord plasma PUFA concentrations were 7.0% and 5.2% (total n-3), 5.0% and 4.6% (DHA+EPA), and 27.9% and 31.4% (total n-6). Mid-pregnancy diet-blood and blood-blood correlations were strongest for DHA+EPA (r=0.38 for diet with maternal blood, r=0.34 for diet with cord blood, r=0.36 for maternal blood with cord blood), and less strong for n-6 PUFA. The FFQ is a reliable measure of elongated PUFA intake, although inter-individual variation is present.
Arnemo, Marianne; Kavaliauskis, Arturas; Andresen, Adriana Magalhaes Santos; Bou, Marta; Berge, Gerd Marit; Ruyter, Bente; Gjøen, Tor
The shortage of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the international markets has led to increasing substitution of fish oil by plant oils in Atlantic salmon (Salmo salar) feed and thereby reducing the EPA and DHA content in salmon. However, the minimum required levels of these fatty acids in fish diets for securing fish health are unknown. Fish were fed with 0, 1 or 2% EPA or DHA alone or in combination of both over a period, growing from 50 to 400 g. Primary head kidney leucocytes were isolated and stimulated with Toll-like receptor (TLR) ligands to determine if EPA and DHA deficiency can affect expression of important immune genes and eicosanoid production. Several genes related to viral immune response did not vary between groups. However, there was a tendency that the high-level EPA and DHA groups expressed lower levels of IL-1β in non-stimulated leucocytes. These leucocytes were also more responsive to the TLR ligands, inducing higher expression levels of IL-1β and Mx1 after stimulation. The levels of prostaglandin E2 and leukotriene B4 in serum and media from stimulated leucocytes were lower in both low and high EPA and DHA groups. In conclusion, leucocytes from low EPA and DHA groups seemed to be less responsive towards immunostimulants, like TLR ligands, indicating that low levels or absence of dietary EPA and DHA may have immunosuppressive effects.
Botsoglou, Evropi; Govaris, Alexander; Ambrosiadis, Ioannis; Fletouris, Dimitrios; Botsoglou, Nikolas
Our previous study has demonstrated the protective effects of olive leaf extracts on the oxidation of pork patties from n-3 fatty acid-enriched meat during refrigerated storage. The target of the present study was to examine these effects during frozen storage. Results showed that frozen storage accelerated (P=0.05) both lipid and protein oxidation in pork patties, but an addition of olive leaf extract at 200mg gallic acid equivalent/kg improved sensory attributes by delaying oxidation of lipids (reduction (P=0.05) of conjugated dienes, hydroperoxides and malondialdehyde), and of proteins (reduction (P=0.05) of protein carbonyls and inhibition (P=0.05) of the decrease of protein sulfhydryls).
Park, Yongsoon; Moon, Hyoun-Jung; Kim, Seok-Hyeon
Epidemiological data and clinical trials suggest that n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have preventive and therapeutic effects on depression; however, the underlying mechanism remains elusive. The present study aimed to examine the behavioral effects and antidepressant mechanism of n-3 PUFA using a forced swimming test. Eleven-week-old male Sprague-Dawley rats were fed an American Institute of Nutrition-93M diet containing 0%, 0.5% or 1% EPA and DHA relative to the total energy intake in their diet for 12 weeks (n=8 per group). Total dietary intake, body weight and hippocampus weights were not significantly different among groups. The groups administered 0.5% and 1% EPA+DHA diets had significantly higher levels of n-3 PUFA in their brain phospholipids compared to those in the control group. The immobility time was significantly decreased and the climbing time was significantly increased in the 0.5% and 1% EPA+DHA groups compared with those in the 0% EPA+DHA group. Plasma serotonin concentration and hippocampus c-AMP response element binding protein (CREB) expression were significantly increased in the 0.5% and 1% EPA+DHA groups compared with those in the 0% EPA+DHA group. Conversely, interleukin (IL)-6 expression was significantly reduced in the 0.5% and 1% EPA+DHA groups compared with that in the 0% EPA+DHA group. However, there were no dose-dependent effects of n-3 PUFA and no significant differences in expressions of IL-1β, tumor necrosis factor-α, brain-derived neurotrophic factor or phosphorylated CREB. In conclusion, long-term intake of EPA+DHA induced antidepressant-like effects in rats and overexpression of CREB via decreased IL-6 expression.
Moussavi, A R Heravi; Gilbert, R O; Overton, T R; Bauman, D E; Butler, W R
The study was designed to test the effects of feeding fish meal (FM) and specific n-3 fatty acids on milk yield and composition, dry matter intake, plasma concentrations of metabolic hormones and metabolites, and liver triglyceride accumulation in early lactating cows. From 5 to 50 d in milk (DIM), cows were fed diets that were isonitrogenous, isoenergetic, and isolipidic containing none (control), 1.25, 2.5, or 5% menhaden FM or 2.3% Ca salts of fish oil fatty acids (CaFOFA). Milk yield (48.2, 49.8, 48.6, 53.5, and 52.2 +/- 1.0 kg/d, respectively) and dry matter intake (22.7, 22.8, 23.0, 23.8, and 24.7 +/- 0.5 kg/d, respectively) differed among diets. Average daily plasma glucose concentration (53.4, 55.3, 51.1, 57.6, and 57.3 +/- 1.3 mg/dL, respectively) was also affected by diet, and plasma insulin concentration was increased by 5% FM and 2.3% Ca-FOFA. At 25 and 50 DIM, blood was collected before feeding and hourly for 11 h after feeding. Plasma glucose concentrations in cows during the day were similar among diets at 25 DIM, but differed at 50 DIM (54.6, 54.4, 52.4, 60.5, and 58.3 +/- 1.4 mg/dL for 0, 1.25, 2.5, and 5% FM or 2.3% CaFOFA, respectively). Plasma insulin was increased in cows fed 5% FM and 2.3% CaFOFA at 25 DIM and was similar among diets at 50 DIM. Dietary treatments had no significant effect on milk composition, energy balance, or on daily plasma concentrations of nonesterified fatty acids, beta-hydroxybutyrate, and urea. Plasma aspartate aminotransferase and hepatic triglyceride concentration in cows did not differ among diets at 21 DIM. Results from this experiment demonstrate that dietary supplementation with FM or n-3 polyunsaturated fatty acids in early lactating dairy cows significantly increased milk yield and DMI with no change in milk composition.
Pontes, P V; Torres, A G; Trugo, N M F; Fonseca, V M; Sichieri, R
Placental transfer of the long-chain polyunsaturated fatty acids (LCPUFA) arachidonic (AA) and docosahexaenoic (DHA) acids is selectively high to maintain accretion to fetal tissues, especially the brain. The objectives of the present study were to investigate the essential fatty acid (EFA) and LCPUFA status at birth of preterm and term Brazilian infants and their mothers, from a population of characteristically low intake of n-3 LCPUFA, and to evaluate the association between fetal and maternal status, by the determination of the fatty acid composition of the erythrocyte membrane. Blood samples from umbilical cord of preterm (26-36 weeks of gestation; n = 30) and term (37-42 weeks of gestation; n = 30) infants and the corresponding maternal venous blood were collected at delivery. The LCPUFA composition of the erythrocyte membrane and DHA status were similar for mothers of preterm and term infants. Neonatal AA was higher (P < 0.01) whereas its precursor 18:2n-6 was lower (P < 0.01) than maternal levels, as expected. There was no difference in LCPUFA erythrocyte composition between preterm and term infants, except for DHA. Term infants presented a worse DHA status than preterm infants (P < 0.01) and than their mothers (P < 0.01) at delivery. There was a negative correlation of neonatal DHA with maternal AA and a positive correlation between neonatal AA and maternal AA and 18:2n-6 only at term. These results suggest that the persistent low DHA maternal status, together with the comparatively better AA and 18:2n-6 status, might have affected maternal-fetal transfer of DHA when gestation was completed up to term, and possibly contributed to the worse DHA status of term neonates compared with the preterm neonates.
Tian, Tao; Zhao, Yunzhao; Huang, Qian; Li, Jieshou
The sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) pathway plays a key role in inflammation. Parenteral nutrition containing n-3 polyunsaturated fatty acids (n-3 PUFA) may regulate inflammatory reactions. The aim of this study is to determine whether n-3 PUFA may improve inflammatory responses by neutralizing SphK1 signaling. Rat models of parenteral nutrition, cecal ligation and puncture (CLP)-induced sepsis were generated. Male Sprague-Dawley rats were operated for CLP on day 2 after venous catheterization. The rats were randomized to receive normal saline (NS; n = 20), parenteral nutrition (PN; n = 20), or PN + fish oil (FO; n = 20) for 5 days. The daily intake of fish oil (1.25-2.82 g EPA and 1.44-3.09 g DHA per 100 ml) in the FO group was approximately 1.8 g/kg body weight/day. Rats in the control group (n = 10) were subjected to sham operation and received a chow diet. Spleen tissues were collected for SphK1 and S1P receptor expression analysis. Our data showed that n-3 PUFA ameliorated the survival rate. SphK1 expression and its enzymatic activity were significantly upregulated in sepsis rats. Furthermore, mRNA and protein levels of S1PR3, but not S1PR1, were also facilitated after CLP. However, PN + FO dramatically decreased SphK1 mRNA level and its enzymatic activity. S1PR3 expression was also attenuated by FO addition. In conclusion, the anti-inflammatory effect of n-3 PUFA may be linked to the inhibition of the SphK1/S1P pathway in a rat model of parenteral nutrition and CLP-induced sepsis.
Karcher, E L; Hill, T M; Bateman, H G; Schlotterbeck, R L; Vito, N; Sordillo, L M; Vandehaar, M J
The ability to reduce incidence of disease in calves and improve early vaccination strategies is of particular interest for dairy producers. The n-3 fatty acids have been reported to reduce inflammatory diseases in humans but limited research has been done in calves. The objective of this study was to compare supplementation of n-3 fatty acids from fish and flax oil on gene expression of whole blood cells and growth of milk-fed Holstein calves. Forty-eight Holstein bull calves from a commercial dairy were randomly assigned to 1 of 3 diets beginning at 4d old: (1) control milk replacer (MR) with all pork fat, (2) MR with 2% flax oil, and (3) MR with 2% fish oil. All MR were 17% fat, 27% crude protein on a dry matter (DM) basis, with all protein from whey sources. Calves were each fed 654g DM of MR daily for the first 25d and then 327g/d for d26, 27, and 28. On d28, calves were challenged with a Pasteurella vaccine and the temperature response to the vaccine was recorded. Milk and feed intake and fecal scores were recorded daily, and body weight and hip width were recorded weekly. Blood was collected from all calves on d25. One tube of collected blood was incubated with endotoxin (lipopolysaccharide; LPS) for 2h and frozen with a second tube of control blood. Quantitative real-time PCR was used to assess the effects of LPS stimulation on cytokine gene expression. During the 28 d, calves supplemented with flax oil had a greater growth rate and feed efficiency than calves fed fish oil (0.52±0.02 vs. 0.48±0.02g of gain:g of feed). Fish oil tended to decrease LPS stimulation of tumor necrosis factor-α expression. Flax oil, but not fish oil, decreased the expression of IL-4 and tended to decrease expression of osteopontin and IL-8. Flax oil tended to reduce the increase in rectal temperature in response to a Pasteurella vaccine. In conclusion, our data support the idea that supplementation with n-3 fatty acids affects cytokine gene expression.
Cattani, M; Mantovani, R; Schiavon, S; Bittante, G; Bailoni, L
The aim of the study was to investigate whether the addition of extruded flaxseed (EF) in dairy cow diets had an effect on milk fat and individual fatty acids (FA) recovery in cheese after 90 d of ripening. Eighteen Holstein-Friesian cows, divided into 3 experimental groups (6 cows/group), were fed 3 isonitrogenous and isoenergetic diets with 0 (CTR), 500 (EF500), or 1,000 g/d (EF1000) of EF in 3 subsequent periods (2 wk/each), following a 3 × 3 Latin square design. Dry matter intake (DMI) and milk yield were recorded daily. Individual milk samples were collected on d 7 and 13 of each period to determine proximate and FA composition. Eighteen cheese-making sessions (2 for each group and period) were carried out, using a representative pooled milk sample obtained from the 6 cows of each group (10L). At 90 d of ripening, cheeses were analyzed for proximate and FA composition. Cheese yield was computed as the ratio between the weights of ripened cheese and processed milk. Recoveries of fat, individual FA, and grouped FA were computed as the ratio between the corresponding weights in cheese and in milk. Inclusion of EF did not affect DMI, milk yield, or milk composition. Compared with CTR, the 2 diets containing EF increased the proportion of C18:3n-3 and total n-3 FA, in both milk and cheese. Cheese yield and cheese fat percentage did not differ among diets. Likewise, milk fat recovery in cheese was comparable in the 3 treatments and averaged 0.85. The recoveries of individual FA were, for the most part, not dissimilar from fat recovery, except for short-chain saturated FA (from 0.38 for C4:0 to 0.80 for C13:0), some long-chain saturated FA (0.56 and 0.62 for C20:0 and C21:0, respectively), and for C18:3n-6 (1.65). The recovery of saturated FA was lower than that of monounsaturated FA, whereas recovery of polyunsaturated FA was intermediate. Compared with medium- and long-chain FA, short-chain FA were recovered to a smaller extent in cheese. No differences in
Sekikawa, Akira; Kadowaki, Takashi; Curb, J David; Evans, Rhobert W; Maegawa, Hiroshi; Abbott, Robert D; Sutton-Tyrrell, Kim; Okamura, Tomonori; Shin, Chol; Edmundowicz, Daniel; Kadota, Aya; Choo, Jina; El-Saed, Aiman; Ueshima, Hirotsugu; Kuller, Lewis H
This study examines the differences in circulating levels of cytokines among Japanese in Japan (JJ), Japanese Americans (JA), and whites and their associations with obesity and marine n-3 fatty acids (FA) in a cross-sectional population-based study of 297 men aged 40-49 (100 JJ, 99 whites, and 98 JA). Experimental studies show that cytokines are associated with obesity positively and marine n-3 FA inversely. Serum interleukin-1alpha (IL-1alpha), IL-1 receptor agonist (IL-1ra), IL-4, IL-8, IL-10, inducible protein-10 (IP-10), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and marine n-3 FA were determined. Body mass index (BMI), waist circumference, and computed tomography-measured visceral and subcutaneous adipose tissues were determined. The JJ had significantly lower levels of IL-1alpha, IL-4, IL-8, MCP-1, and TNF-alpha than whites and JA. Whites and JA had similar levels of IL-1alpha, IL-4, and IL-8 whereas whites had significantly higher levels of MCP-1 and TNF-alpha than JA. The JJ were least obese (BMI (kg/m(2)), mean +/- standard deviation) 23.6 +/- 2.8, 27.9 +/- 4.6, and 27.9 +/- 4.5 for JJ, whites, and JA, respectively. The JJ had marine n-3 FA about 100% higher than whites and JA (serum marine n-3 FA (%), median (interquartile range) 8.79 (7.41, 11.16), 3.47 (2.63, 4.83), and 4.44 (3.33, 6.01) for JJ, whites, and JA, respectively). Generally cytokines had weak and nonsignificant associations with indices of obesity and nonsignificant associations with marine n-3 FA. BMI had significant inverse associations with IL-1alpha, IL-4, and IL-8 in JA (P < 0.05). Marine n-3 FA had marginally significant inverse associations with IL-8 in JJ (P = 0.055) and TNF-alpha in whites (P = 0.076). The JJ had lower levels of many cytokines than whites and JA. Generally cytokines had weak and nonsignificant associations with indices of obesity and marine n-3 FA. Further investigation is needed to determine why JJ had lower circulating
Shen, Wenwen; Wang, Cui; Xia, Lulu; Fan, Chaonan; Dong, Hua; Deckelbaum, Richard J.; Qi, Kemin
We report evidence of a detailed epigenetic modification of the leptin promoter and the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), which is closely associated with the leptin gene transcription in obesity. In the adipose tissue of diet induced obese (DIO) mice, methylation of the CpG island and the binding of methyl-CpG-binding domain protein 2 (MBD2) and DNA methyltransferases (DNMTs) at the leptin promoter are increased and RNA Pol II is decreased. Additionally, histones H3 and H4 are hypoacetylated, lysine 4 of histone H3 (H3K4) is hypomethylated and the binding of histone deacetylases (HDACs) 1, 2 and 6 is increased at the leptin promoter in the DIO mice. These modifications may serve a feedback role to maintain leptin concentrations within a normal range. The regulation of leptin transcriptional expression by n-3 PUFAs is mediated, at least in part, by epigenetic targets, such as MBD2 and histone modifications. PMID:24923522
Li, Q; Leung, Y O; Zhou, I; Ho, L C; Kong, W; Basil, P; Wei, R; Lam, S; Zhang, X; Law, A C K; Chua, S E; Sham, P C; Wu, E X; McAlonan, G M
Prenatal exposure to maternal immune activation (MIA) increases the risk of schizophrenia and autism in the offspring. The MIA rodent model provides a valuable tool to directly test the postnatal consequences of exposure to an early inflammatory insult; and examine novel preventative strategies. Here we tested the hypotheses that behavioural differences in the MIA mouse model are accompanied by in vivo and ex vivo alterations in brain biochemistry; and that these can be prevented by a post-weaning diet enriched with n-3 polyunsaturated fatty acid (PUFA). The viral analogue PolyI:C (POL) or saline (SAL) was administered to pregnant mice on gestation day 9. Half the resulting male offspring (POL=21; SAL=17) were weaned onto a conventional lab diet (n-6 PUFA); half were weaned onto n-3 PUFA-enriched diet. In vivo magnetic resonance spectroscopy measures were acquired prior to behavioural tests; glutamic acid decarboxylase 67 (GAD67) and tyrosine hydroxylase protein levels were measured ex vivo. The main findings were: (i) Adult MIA-exposed mice fed a standard diet had greater N-acetylaspartate/creatine (Cr) and lower myo-inositol/Cr levels in the cingulate cortex in vivo. (ii) The extent of these metabolite differences was correlated with impairment in prepulse inhibition. (iii) MIA-exposed mice on the control diet also had higher levels of anxiety and altered levels of GAD67 ex vivo. (iv) An n-3 PUFA diet prevented all the in vivo and ex vivo effects of MIA observed. Thus, n-3 PUFA dietary enrichment from early life may offer a relatively safe and non-toxic approach to limit the otherwise persistent behavioural and biochemical consequences of prenatal exposure to inflammation. This result may have translational importance.
Childs, C E; Hoile, S P; Burdge, G C; Calder, P C
The mechanisms responsible for changes to long-chain polyunsaturated fatty acid (LC PUFA) status during pregnancy have not been fully elucidated. Tissue samples were collected from virgin and pregnant (day 12 and 20) female rats. LC PUFA status, sex hormone concentrations and hepatic mRNA expression of FADS1, FADS2 and elongase were assessed. Day 20 gestation females had higher plasma and liver docosahexaenoic acid and lower arachidonic acid content than virgin females (P<0.05). There was higher FADS2 mRNA expression during pregnancy (P=0.051). Progesterone and oestradiol concentrations positively correlated with hepatic FADS2 mRNA expression (P=0.043, P=0.004). Progesterone concentration positively correlated with hepatic n-6 docosapentaenoic acid content (P=0.006), and inversely correlated with intermediates in LC PUFA synthesis including n-3 docosapentaenoic acid, γ-linolenic acid and 20:2n-6 (P<0.05). Changes in progesterone and oestradiol during pregnancy may promote the synthesis of LC PUFA via increased FADS2 expression.
Finocchiaro, Concetta; Segre, Olivia; Fadda, Maurizio; Monge, Taira; Scigliano, Mara; Schena, Marina; Tinivella, Marco; Tiozzo, Elisa; Catalano, Maria G; Pugliese, Mariateresa; Fortunati, Nicoletta; Aragno, Manuela; Muzio, Giuliana; Maggiora, Marina; Oraldi, Manuela; Canuto, Rosa A
PUFA from fish oil appear to have anti-inflammatory and anti-oxidative effects and improve nutritional status in cancer patients. With this as background, the aim of the present study was to investigate the effect of EPA plus DHA on inflammatory condition, and oxidative and nutritional status in patients with lung cancer. In our multicentre, randomised, double-blind trial, thirty-three patients with a diagnosis of advanced inoperable non-small-cell lung cancer and undergoing chemotherapy were divided into two groups, receiving four capsules/d containing 510 mg of EPA and 340 mg of DHA, or 850 mg of placebo, for 66 d. At the start of chemotherapy (T₀), after 8 d (T₁), 22 d (T₂) and 66 d (T₃), biochemical (inflammatory and oxidative status parameters) and anthropometric parameters were measured in both groups. A significant increase of body weight in the n-3 group at T₃ v. T₀ was observed. Concerning inflammation, C-reactive protein and IL-6 levels differed significantly between the n-3 and placebo groups at T₃, and progressively decreased during chemotherapy in the n-3 group, evidencing n-3 PUFA anti-inflammatory action. Concerning oxidative status, plasma reactive oxygen species levels increased in the placebo group v. the n-3 group at the later treatment times. Hydroxynonenal levels increased in the placebo group during the study, while they stabilised in the n-3 group. Our data confirm that the continual assumption of EPA plus DHA determined an anti-inflammatory and anti-oxidative action which could be considered a preliminary goal in anti-cachectic therapy.
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
Michaelsen, Kim F; Dewey, Kathryn G; Perez-Exposito, Ana B; Nurhasan, Mulia; Lauritzen, Lotte; Roos, Nanna
With increasing interest in the potential effects of n-6 and n-3 fatty acids in early life, there is a need for data on the dietary intake of polyunsaturated fatty acids (PUFA) in low-income countries. This review compiles information on the content in breast milk and in foods that are important in the diets of low-income countries from the few studies available. We also estimate the availability of fat and fatty acids in 13 low-income and middle-income countries based on national food balance sheets from the United Nations' Food and Agriculture Organization Statistical Database (FOASTAT). Breast milk docosahexaenoic acid content is very low in populations living mainly on a plant-based diet, but higher in fish-eating countries. Per capita supply of fat and n-3 fatty acids increases markedly with increasing gross domestic product (GDP). In most of the 13 countries, 70-80% of the supply of PUFA comes from cereals and vegetable oils, some of which have very low α-linolenic acid (ALA) content. The total n-3 fatty acid supply is below or close to the lower end of the recommended intake range [0.4%E (percentage of energy supply)] for infants and young children, and below the minimum recommended level (0.5%E) for pregnant and lactating women in the nine countries with the lowest GDP. Fish is important as a source of long-chain n-3 fatty acids, but intake is low in many countries. The supply of n-3 fatty acids can be increased by using vegetable oils with higher ALA content (e.g. soybean or rapeseed oil) and by increasing fish production (e.g. through fish farming).
Li, Kelei; Huang, Tao; Zheng, Jusheng; Wu, Kejian; Li, Duo
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
The objective of this study was to investigate the effect of incremental amounts of ground flaxseed (GFLAX) on milk yield and fatty acids (FA) profile, ruminal metabolism, and nutrient digestibility in dairy cows fed high-forage diets. Twelve multiparous Jersey cows averaging (mean ± SD) 112 ± 68 da...
Ruth, Megan R; Proctor, Spencer D; Field, Catherine J
Dietary EPA and DHA modulate immunity and thereby may improve the aberrant immune function in obese states. To determine the effects of feeding fish oil (FO) containing EPA and DHA on splenocyte phospholipid (PL) and lipid-raft fatty acid composition, phenotypes and cytokine production, 14-week-old obese, leptin receptor-deficient JCR:LA-cp rats (cp/cp; n 10) were randomised to one of three nutritionally adequate diets for 3 weeks: control (Ctl, 0 % EPA+DHA); low FO (LFO, 0.8 % (w/w) EPA+DHA); high FO (HFO, 1.4 % (w/w) EPA+DHA). Lean JCR:LA-cp (+/ - or +/+) rats (n 5) were fed the Ctl diet. Obese Ctl rats had a higher proportion of n-3 PUFA in splenocyte PL than lean rats fed the same diet (P < 0.05). The lower n-6:n-3 PUFA ratio of splenocyte PL was consistent with the lower mitogen-stimulated interferon (IFN)-gamma and IL-1beta production by cells from obese rats (P < 0.05). Obese rats fed the FO diet had lower mitogen-stimulated Th1 (IFN-gamma) and Th2 (IL-4) cytokine responses, but IL-2 production (concanavalin A; ConA) did not differ (P < 0.05). The HFO diet was more effective in lowering IL-1beta and increasing IL-10 production (ConA, P < 0.05). This lower IL-1beta production was accompanied by a lower proportion of major histocompatability complex class II-positive cells and a higher incorporation of DHA into lipid rafts. This is the first study to demonstrate impaired responses to mitogen stimulation and altered fatty acid incorporation into the membrane PL of JCR:LA-cp rats. Feeding FO lowered the ex vivo inflammatory response, without altering IL-2 production from ConA-stimulated splenocytes which may occur independent of leptin signalling.
Kagohashi, Yukiko; Abiru, Norio; Kobayashi, Masakazu; Hashimoto, Michio; Shido, Osamu; Otani, Hiroki
Environment factors, including maternal or infant dietary nutrition have been reported to have an influence on the pathogenesis of type 1 diabetes. In the present study, to investigate the effect of maternal or post-weaning offspring's nutrition, in particular the essential fatty acid ratio (n-6/n-3) on the development of type 1 diabetes, we prepared two kinds of chows with n-6/n-3 ratios of 3.0 (L) and 14.5 (H), and provided them to mothers of non-obese diabetic (NOD) mice during gestation and lactation and to the offspring after weaning. The n-6/n-3 ratios in breast milk and erythrocyte membrane of NOD offspring became nearly the same with that of the maternal diet at 2 weeks after birth. In the L chow-fed offspring from L chow-fed mother (LLL), levels of insulitis were higher than those in the H chow-fed offspring from H chow-fed mother (HHH) at 4 weeks of age, while the levels in the LLL offspring became lower than those in the HHH after 6 weeks. Early insulin autoantibody expressions were found from 2 to 6 weeks in the HHH offspring, but not in the LLL. The LLL offspring exhibited strong suppression of overt diabetes development in regard to the onset and accumulated incidence of diabetes compared to the HHH. The study with combined L and H chows during gestation, lactation in mother and in post-weaning offspring revealed that only the LLH chow significantly suppressed the development of diabetes with similar kinetics to LLL chow, although the other combinations may delay the onset of diabetes. The present findings suggest that n-6/n-3 ratio of the maternal diet during gestation and lactation rather than that of offspring after weaning strongly affects the development of overt diabetes in NOD mice.
Tammam, Jonathan D; Steinsaltz, David; Bester, D W; Semb-Andenaes, Turid; Stein, John F
Nutrient deficiencies have been implicated in anti-social behaviour in schoolchildren; hence, correcting them may improve sociability. We therefore tested the effects of vitamin, mineral and n-3 supplementation on behaviour in a 12-week double-blind randomised placebo-controlled trial in typically developing UK adolescents aged 13-16 years (n 196). Changes in erythrocyte n-3 and 6 fatty acids and some mineral and vitamin levels were measured and compared with behavioural changes, using Conners' teacher ratings and school disciplinary records. At baseline, the children's PUFA (n-3 and n-6), vitamin and mineral levels were low, but they improved significantly in the group treated with n-3, vitamins and minerals (P=0·0005). On the Conners disruptive behaviour scale, the group given the active supplements improved, whereas the placebo group worsened (F=5·555, d=0·35; P=0·02). The general level of disciplinary infringements was low, thus making it difficult to obtain improvements. However, throughout the school term school disciplinary infringements increased significantly (by 25 %; Bayes factor=115) in both the treated and untreated groups. However, when the subjects were split into high and low baseline infringements, the low subset increased their offences, whereas the high-misbehaviour subset appeared to improve after treatment. But it was not possible to determine whether this was merely a statistical artifact. Thus, when assessed using the validated and standardised Conners teacher tests (but less clearly when using school discipline records in a school where misbehaviour was infrequent), supplementary nutrition might have a protective effect against worsening behaviour.
Paletz, Elliott M; Day, Jeremy J; Craig-Schmidt, Margaret C; Newland, M Christopher
Fish contain essential long chain polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), an omega-3 (or n-3) PUFA, but are also the main source of exposure to methylmercury (MeHg), a potent developmental neurotoxicant. Since n-3 PUFAs support neural development and function, benefits deriving from a diet rich in n-3s have been hypothesized to protect against deleterious effects of gestational MeHg exposure. To determine whether protection occurs at the behavioral level, female Long-Evans rats were exposed, in utero, to 0, 0.5, or 5ppm of Hg as MeHg via drinking water, approximating exposures of 0, 40, and 400 microgHg/kg/day and producing 0, 0.29, and 5.50ppm of total Hg in the brains of siblings at birth. They also received pre- and postnatal exposure to one of two diets, both based on the AIN-93 semipurified formulation. A "fish-oil" diet was high in, and a "coconut-oil" diet was devoid of, DHA. Diets were approximately equal in alpha-linolenic acid and n-6 PUFAs. As adults, the rats were first assessed with a spatial discrimination reversal (SDR) procedure and later with a visual (nonspatial) discrimination reversal (VDR) procedure. MeHg increased the number of errors to criterion for both SDR and VDR during the first reversal, but effects were smaller or non-existent on the original discrimination and on later reversals. No such MeHg-related deficits were seen when the rats were retested on SDR after 2 years of age. These results are consistent with previous reports and hypotheses that gestational MeHg exposure produces perseverative responding. No interactions between diet and MeHg were found, suggesting that n-3 PUFAs do not guard against these behavioral effects. Brain Hg concentrations did not differ between the diets, either. In geriatric rats, failures to respond were less common and response latencies were shorter for rats fed the fish-oil diet, suggesting that exposure to a diet rich in n-3s may lessen the impact of age
Paletz, Elliott M.; Day, Jeremy J.; Craig-Schmidt, Margaret C.; Newland, M. Christopher
Fish contain essential long chain polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), an omega-3 (or n-3) PUFA, but are also the main source of exposure to methylmercury (MeHg), a potent developmental neurotoxicant. Since n-3 PUFAs support neural development and function, benefits deriving from a diet rich in n-3s have been hypothesized to protect against deleterious effects of gestational MeHg exposure. To determine whether protection occurs at the behavioral level, female Long-Evans rats were exposed, in utero, to 0, 0.5, or 5 ppm of Hg as MeHg via drinking water, approximating exposures of 0, 40, and 400 μg Hg/kg/day and producing 0, 0.29, and 5.50 ppm of total Hg in the brains of siblings at birth. They also received pre- and postnatal exposure to one of two diets, both based on the AIN-93 semipurified formulation. A “fish-oil” diet was high in, and a “coconut-oil” diet was devoid of, DHA. Diets were approximately equal in α-linolenic acid and n-6 PUFAs. As adults, the rats were first assessed with a spatial discrimination reversal (SDR) procedure and later with a visual (nonspatial) discrimination reversal (VDR) procedure. MeHg increased the number of errors to criterion for both SDR and VDR during the first reversal, but effects were smaller or nonexistent on the original discrimination and on later reversals. No such MeHg-related deficits were seen when the rats were retested on SDR after two years of age. These results are consistent with previous reports and hypotheses that gestational MeHg exposure produces perseverative responding. No interactions between Diet and MeHg were found, suggesting that n-3 PUFAs do not guard against these behavioral effects. Brain Hg concentrations did not differ between the diets, either. In geriatric rats, failures to respond were less common and response latencies were shorter for rats fed the fish oil diet, suggesting that exposure to a diet rich in n-3s may lessen the impact of age
Salcedo-Sandoval, Lorena; Cofrades, Susana; Ruiz-Capillas, Claudia; Matalanis, Alison; McClements, D Julian; Decker, Eric A; Jiménez-Colmenero, Francisco
The effect of storage time (2°C, 19 days) and heating (70°C, 30 min) on physical characteristics and oxidative stability of fish oil encapsulated in filled hydrogel particles was determined and compared with a conventional oil-in-water (O/W) emulsion with the same oil content (8.5%). Subsequently they were used to enrich meat systems with n-3 LCPUFAs, and their lipid oxidation was evaluated and compared with two other meat systems: one containing all animal fat and another with fish oil added directly. Filled hydrogel particles were more effective in lowering the oxidation rate than O/W emulsion, even when thermal treatment was applied. Oxidative stability over the storage time was best in the n-3 LCPUFA-enriched meat system containing filled hydrogel particles, in which TBARS levels were up to 62% lower than other systems containing fish oil. Hydrogel particles offer a promising means of controlling lipid oxidation in n-3 LCPUFA-enriched meat products.
Lohner, Szimonetta; Fekete, Katalin; Decsi, Tamás
The mainstream of phenylketonuria (PKU) management is lifelong restriction of protein intake; however, this dietary restriction may be accompanied by insufficient dietary intake of long-chain polyunsaturated fatty acids (LCPUFA). The objective of this review was to assess whether significant depletion of LCPUFA can be detected in PKU patients on low-protein diet and whether LCPUFA supplementation is an effective way to increase the availability of LCPUFA in PKU patients. The method included structured search strategy on Ovid MEDLINE, Scopus, LILACS, and the Cochrane Library CENTRAL databases, with formal inclusion/exclusion criteria, data extraction procedure, and meta-analysis. We evaluated 9 case-control studies and 6 randomized controlled trials, dated from the inception of the databases to 2012. The meta-analysis of the case-control studies showed significantly lower values of both eicosapentaenoic acid and docosahexaenoic acid (DHA) in all biomarkers investigated and that of arachidonic acid in total plasma lipids in PKU patients as compared with healthy controls. There were sufficient data to demonstrate that dietary DHA supplementation of patients with PKU significantly increases the contribution of DHA to total plasma lipids. In summary, suboptimal LCPUFA status, especially that of n-3 LCPUFA, can be detected in PKU patients. Supplementing DHA to the diet of PKU patients may improve their LCPUFA status; however, further research is needed to determine the optimal supplementation dosage and to establish beneficial functional outcomes.
Green, Joshua T.; Liu, Zhen; Bazinet, Richard P.
Previous studies have infused radiolabeled arachidonic acid (AA) into rat brains and followed AA esterification into phospholipids for up to 24 h; however, the half-life of AA in rat brain phospholipids is unknown. Eighteen day old rats were fed either an n-3 PUFA adequate or deprived diet for 15 weeks. Following the 15 weeks, 40 µCi of [3H] AA was injected intracerebroventricularly into the right lateral ventricle using stereotaxic surgery and returned to their dietary treatment. From 4–120 days after [3H] AA administration, brains were collected for chemical analyses. The half-life of AA in rat brain phospholipids was 44 ± 4 days for the n-3 PUFA adequate group and 46 ± 4 days for the n-3 PUFA deprived group, which closely approximates the predicted half-life previously reported, based on the rate of entry from the plasma unesterified pool, suggesting the plasma unesterified pool is a major contributor to brain uptake of AA. Furthermore, unlike a previous report in which the half-life of brain phospholipid docosahexaenoic acid (DHA) was increased in n-3 PUFA deprived rats, n-3 PUFA deprivation did not significantly alter the AA half-life, suggesting different mechanisms exist to maintain brain concentrations of AA and DHA. PMID:19661256
Kendall, Alexandra C; Kiezel-Tsugunova, Magdalena; Brownbridge, Luke C; Harwood, John L; Nicolaou, Anna
Ceramides are important for skin health, with a multitude of species found in both dermis and epidermis. The epidermis contains linoleic acid-Ester-linked Omega-hydroxylated ceramides of 6-Hydroxy-sphingosine, Sphingosine and Phytosphingosine bases (CER[EOH], CER[EOS] and CER[EOP], respectively), that are crucial for the formation of the epidermal barrier, conferring protection from environmental factors and preventing trans-epidermal water loss. Furthermore, a large number of ceramides, derivatives of the same sphingoid bases and various fatty acids, are produced by dermal and epidermal cells and perform signalling roles in cell functions ranging from differentiation to apoptosis. Supplementation with the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise as therapeutic agents in a number of inflammatory skin conditions, altering the lipid profile of the skin and production of bioactive lipids such as the eicosanoids, docosanoids and endocannabinoids. In this study we wished to investigate whether EPA and DHA could also affect the ceramide profile in epidermis and dermis, and, in this way, contribute to formation of a robust lipid barrier and ceramide-mediated regulation of skin functions. Ex vivo skin explants were cultured for 6days, and supplemented with EPA or DHA (50μM). Liquid chromatography coupled to tandem mass spectrometry with electrospray ionisation was used to assess the prevalence of 321 individual ceramide species, and a number of sphingoid bases, phosphorylated sphingoid bases, and phosphorylated ceramides, within the dermis and epidermis. EPA augmented dermal production of members of the ceramide families containing Non-hydroxy fatty acids and Sphingosine or Dihydrosphingosine bases (CER[NS] and CER[NDS], respectively), while epidermal CER[EOH], CER[EOS] and CER[EOP] ceramides were not affected. DHA did not significantly affect ceramide production. Ceramide-1-phosphate levels in
Incorporation of marine lipids into mitochondrial membranes increases susceptibility to damage by calcium and reactive oxygen species: evidence for enhanced activation of phospholipase A2 in mitochondria enriched with n-3 fatty acids.
Malis, C D; Weber, P C; Leaf, A; Bonventre, J V
Experiments were designed to evaluate the susceptibility of mitochondrial membranes enriched with n-3 fatty acids to damage by Ca2+ and reactive oxygen species. Fatty acid content and respiratory function were assessed in renal cortical mitochondria isolated from fish-oil- and beef-tallow-fed rats. Dietary fish oils were readily incorporated into mitochondrial membranes. After exposure to Ca2+ and reactive oxygen species, mitochondria enriched in n-3 fatty acids, and using pyruvate and malate as substrates, had significantly greater changes in state 3 and uncoupled respirations, when compared with mitochondria from rats fed beef tallow. Mitochondrial site 1 (NADH coenzyme Q reductase) activity was reduced to 45 and 85% of control values in fish-oil- and beef-tallow-fed groups, respectively. Exposure to Ca2+ and reactive oxygen species enhance the release of polyunsaturated fatty acids enriched at the sn-2 position of phospholipids from mitochondria of fish-oil-fed rats when compared with similarly treated mitochondria of beef-tallow-fed rats. This release of fatty acids was partially inhibited by dibucaine, the phospholipase A2 inhibitor, which we have previously shown to protect mitochondria against damage associated with Ca2+ and reactive oxygen species. The results indicate that phospholipase A2 is activated in mitochondria exposed to Ca2+ and reactive oxygen species and is responsible, at least in part, for the impairment of respiratory function. Phospholipase A2 activity and mitochondrial damage are enhanced when mitochondrial membranes are enriched with n-3 fatty acids. PMID:2123344
Supplementation with N-3 Long-Chain Polyunsaturated Fatty Acids or Olive Oil in Men and Women with Renal Disease Induces Differential Changes in the DNA Methylation of FADS2 and ELOVL5 in Peripheral Blood Mononuclear Cells
Hoile, Samuel P.; Clarke-Harris, Rebecca; Huang, Rae-Chi; Calder, Philip C.; Mori, Trevor A.; Beilin, Lawrence J.; Lillycrop, Karen A.; Burdge, Graham C.
Background Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans. Methods and Results We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5′ regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (>10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (>10%) 1/12 ELOVL5 CpGs in men. OO altered (>6%) 8/22 FADS2 CpGs and (>3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (>5%) 3/22 FADS2 CpGs and 2/12 (>3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts. Conclusions These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function. PMID:25329159
Abdukeyum, Grace G.; Owen, Alice J.; Larkin, Theresa A.; McLennan, Peter L.
Reactive oxygen species paradoxically underpin both ischaemia/reperfusion (I/R) damage and ischaemic preconditioning (IPC) cardioprotection. Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) are highly susceptible to peroxidation, but are paradoxically cardioprotective. This study tested the hypothesis that LCn-3 PUFA cardioprotection is underpinned by peroxidation, upregulating antioxidant activity to reduce I/R-induced lipid oxidation, and the mechanisms of this nutritional preconditioning contrast to mechanisms of IPC. Rats were fed: fish oil (LCn-3 PUFA); sunflower seed oil (n-6 PUFA); or beef tallow (saturated fat, SF) enriched diets for six weeks. Isolated hearts were subject to: 180 min normoxic perfusion; a 30 min coronary occlusion ischaemia protocol then 120 min normoxic reperfusion; or a 3 × 5 min global IPC protocol, 30 min ischaemia, then reperfusion. Dietary LCn-3 PUFA raised basal: membrane docosahexaenoic acid (22:6n-3 DHA); fatty acid peroxidisability index; concentrations of lipid oxidation products; and superoxide dismutase (MnSOD) activity (but not CuZnSOD or glutathione peroxidase). Infarct size correlated inversely with basal MnSOD activity (r2 = 0.85) in the ischaemia protocol and positively with I/R-induced lipid oxidation (lipid hydroperoxides (LPO), r2 = 0.475; malondialdehyde (MDA), r2 = 0.583) across ischaemia and IPC protocols. While both dietary fish oil and IPC infarct-reduction were associated with reduced I/R-induced lipid oxidation, fish oil produced nutritional preconditioning by prior LCn-3 PUFA incorporation and increased peroxidisability leading to up-regulated mitochondrial SOD antioxidant activity. PMID:26959067
Fortin, M.; Julien, P.; Couture, Y.; Dubreuil, P.; Chouinard, P. Y.; Latulippe, C.; Davis, T. A.; Thivierge, M. C.
A previous study showed that long-chain n-3 polyunsaturated fatty acids (LCn-3PUFA; >18 carbons n-3) exert an anabolic effect on protein metabolism through the upregulation of insulin sensitivity and activation of the insulin signaling pathway. This study further delineates for the first time whether the anabolic effect of LCn-3PUFA on metabolism is dose responsive. Six steers were used to test three graded amounts of menhaden oil rich in LCn-3PUFA (0%, 2% and 4%; enteral infusions) according to a double 3 × 3 Latin square design. Treatment comparisons were made using iso-energetic substitutions of control oil for menhaden oil and using 6-week experimental periods. The LCn-3PUFA in muscle total membrane phospholipids increased from 8%, 14% to 20% as dietary menhaden oil increased. Feeding graded amounts of menhaden oil linearly decreased plasma insulin concentration (49, 35 and 25 μU/ml, P = 0.01). The insulin-stimulated amino acid disposal rates as assessed using hyperinsulinemic–euglycemic–euaminoacidemic clamps (20, 40 and 80 mU/kg per h) were linearly increased by the incremental administrations of menhaden oil from 169, 238 to 375 μmol/kg per h (P = 0.005) during the 40 mU/kg per h clamp, and from 295, 360 and 590 mmol/kg per h (P = 0.02) during the 80 mU/kg per h clamp. Glucose disposal rate responded according to a quadratic relationship with the incremental menhaden oil amounts (P < 0.05). A regression analysis showed that 47% of the amino acid disposal rates elicited during the hyperinsulinemic clamp was related to muscle membrane LCn-3PUFA content (P = 0.003). These results show for the first time that both protein and glucose metabolism respond in a dose-dependent manner to menhaden oil and to muscle membrane LCn-3PUFA. PMID:22443622
Prescription n-3 fatty acids, but not eicosapentaenoic acid alone, improve reference memory-related learning ability by increasing brain-derived neurotrophic factor levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.
Hashimoto, Michio; Inoue, Takayuki; Katakura, Masanori; Tanabe, Yoko; Hossain, Shahdat; Tsuchikura, Satoru; Shido, Osamu
Metabolic syndrome is implicated in the decline of cognitive ability. We investigated whether the prescription n-3 fatty acid administration improves cognitive learning ability in SHR.Cg-Lepr(cp)/NDmcr (SHR-cp) rats, a metabolic syndrome model, in comparison with administration of eicosapentaenoic acid (EPA, C20:5, n-3) alone. Administration of TAK-085 [highly purified and concentrated n-3 fatty acid formulation containing EPA ethyl ester and docosahexaenoic acid (DHA, C22:6, n-3) ethyl ester] at 300 mg/kg body weight per day for 13 weeks reduced the number of reference memory-related errors in SHR-cp rats, but EPA alone had no effect, suggesting that long-term TAK-085 administration improves cognitive learning ability in a rat model of metabolic syndrome. However, the working memory-related errors were not affected in either of the rat groups. TAK-085 and EPA administration increased plasma EPA and DHA levels of SHR-cp rats, associating with an increase in EPA and DHA in the cerebral cortex. The TAK-085 administration decreased the lipid peroxide levels and reactive oxygen species in the cerebral cortex and hippocampus of SHR-cp rats, suggesting that TAK-085 increases antioxidative defenses. Its administration also increased the brain-derived neurotrophic factor levels in the cortical and hippocampal tissues of TAK-085-administered rats. The present study suggests that long-term TAK-085 administration is a possible therapeutic strategy for protecting against metabolic syndrome-induced learning decline.
A randomised controlled trial investigating the effect of n-3 long-chain polyunsaturated fatty acid supplementation on cognitive and retinal function in cognitively healthy older people: the Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) study protocol [ISRCTN72331636
Dangour, Alan D; Clemens, Felicity; Elbourne, Diana; Fasey, Nicky; Fletcher, Astrid E; Hardy, Pollyanna; Holder, Graham E; Huppert, Felicia A; Knight, Rosemary; Letley, Louise; Richards, Marcus; Truesdale, Ann; Vickers, Madge; Uauy, Ricardo
The number of individuals with age-related cognitive impairment is rising dramatically in the UK and globally. There is considerable interest in the general hypothesis that improving the diet of older people may slow the progression of cognitive decline. To date, there has been little attention given to the possible protective role of n-3 long-chain polyunsaturated fatty acids (n-3 LCPs) most commonly found in oily fish, in age-related loss of cognitive function. The main research hypothesis of this study is that an increased dietary intake of n-3 LCPs will have a positive effect on cognitive performance in older people in the UK. To test this hypothesis, a double-blind randomised placebo-controlled trial will be carried out among adults aged 70–79 years in which the intervention arm will receive daily capsules containing n-3 LCP (0.5 g/day docosahexaenoic acid and 0.2 g/day eicosapentaenoic acid) while the placebo arm will receive daily capsules containing olive oil. The main outcome variable assessed at 24 months will be cognitive performance and a second major outcome variable will be retinal function. Retinal function tests are included as the retina is a specifically differentiated neural tissue and therefore represents an accessible window into the functioning of the brain. The overall purpose of this public-health research is to help define a simple and effective dietary intervention aimed at maintaining cognitive and retinal function in later life. This will be the first trial of its kind aiming to slow the decline of cognitive and retinal function in older people by increasing daily dietary intake of n-3 LCPs. The link between cognitive ability, visual function and quality of life among older people suggests that this novel line of research may have considerable public health importance. PMID:16945130
Excessive secretion of angiotensinogen (Agt) and other adipokines such as Interleukin-6 (IL-6) and Monocyte chemotactic protein-1 (MCP-1) have been linked to obesity and associated metabolic disorders, with a common feature being inflammation. We have previously shown that n-3 polyunsaturated fatty ...
Bergeron, Karen; Julien, Pierre; Davis, Teresa A.; Myre, Alexandre; Thivierge, M. Carole
This study investigated the role of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFAs) of muscle phospholipids in the regulation of neonatal metabolism. Twenty-eight piglets were weaned at 2 days of age and raised on one of two milk formulas that consisted of either a control formula supplying 0% or a formula containing 3.5% LCn-3PUFAs until 10 or 28 days of age. There was a developmental decline in the insulin sensitivity of amino acid disposal in control pigs during the first month of life, with a slope of −2.24 μmol·kg−1·h−1 (P = 0.01) per unit of insulin increment, as assessed using hyperinsulinemic-euglycemic-euaminoacidemic clamps. LCn-3PUFA feeding blunted this developmental decline, resulting in differing insulin sensitivities (P < 0.001). When protein metabolism was assessed under parenteral feeding-induced hyperinsulinemia, LCn-3PUFAs reduced by 16% whole body oxidative losses of amino acids (from 238 to 231 μmol·kg−1·h−1; P = 0.06), allowing 41% more amino acids to accrete into body proteins (from 90 to 127 μmol·kg−1·h−1; P = 0.06). The fractional synthetic rate of muscle mixed proteins remained unaltered by the LCn-3PUFA feeding. However, LCn-3PUFAs retarded a developmental increase in the essential-to-nonessential amino acid ratio of the muscle intracellular free pool (P = 0.05). Overall, alterations in metabolism were concomitant with a preferential incorporation of LCn-3PUFAs into muscle total membrane phospholipids (P < 0.001), in contrast to intramuscular triglycerides. These results underscore the potential role of LCn-3PUFAs as regulators of different aspects of protein metabolism in the neonate. PMID:17673528
Daak, Ahmed A; Elderdery, Abozer Y; Elbashir, Leana M; Mariniello, Katia; Mills, Jeremy; Scarlett, Garry; Elbashir, Mustafa I; Ghebremeskel, Kebreab
Chronic inflammation and reduced blood levels of omega-3 fatty acids (n-3) are known characteristics of sickle cell disease (SCD).The anti-inflammatory properties of n-3 fatty acids are well recognized. Omega-3 treated (n = 24), hydroxyurea (HU) treated (n = 18), and n-3 untreated (n=21) homozygous SCD patients (HbSS) and healthy (HbAA) controls (n = 25) matched for age (5-16 years), gender and socioeconomic status were studied. According to age (5-10) or (11-16) years, two or three capsules containing 277.8 mg docosahexaenoic (DHA) and 39.0mg eicosapentaenoic (EPA) or high oleic acid placebo (41%) were assigned to n-3 treated and n-3 untreated groups, respectively. Hydroxyurea treated group was on dosage more than 20 mg/kg/day. The effect of supplementation on systemic and blood cell markers of inflammation was investigated. The n-3 treated group had higher levels of DHA and EPA (p < 0.001) and lower white blood cell count and monocyte integrin (p < 0.05) compared with the n-3 untreated. No difference was detected between the two groups regarding C-reactive protein, granulocytes integrin and selectin, plasma tumour necrosis factor-α and interleukin-10. The n-3 treated group had lowered nuclear factor-kappa B (NF-κB) gene expression compared to n-3 untreated and HU treated groups (p < 0.05). This study provides evidence that supplementation with n-3 fatty acids may ameliorate inflammation and blood cell adhesion in patients with SCD.
Grenon, S. Marlene; Conte, Michael S.; Nosova, Emily; Alley, Hugh; Chong, Karen; Harris, William S.; Vittinghoff, Eric; Owens, Christopher D.
Objective The n-3 polyunsaturated fatty acids (PUFA) are dietary components derived from fish oil with beneficial cardiovascular effects that may relate in part to anti-inflammatory properties. Peripheral artery disease (PAD) is characterized by a marked pro-inflammatory state. We hypothesized that the n-3 PUFA content of red blood cells (omega-3 index) would be correlated with biomarkers of inflammation and vascular function in a PAD cohort. Methods This was a cross-sectional study of subjects who presented to an outpatient vascular surgery clinic for evaluation of PAD. We used linear regression to evaluate the independent association between the omega-3 index, inflammatory biomarkers [C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), and tumor-necrosis-factor-α (TNF-α)] and endothelial function (brachial artery flow mediated dilation [FMD]). Results 64 subjects (61 claudicants and 3 with critical limb ischemia) were recruited for the study. The mean CRP level was 5.0 ± 5.0 mg/L and the mean omega-3 index was 5.0% ± 1.8%. In an unadjusted model, the omega-3 index was negatively associated with CRP (38% increase in CRP for one standard deviation decrease in the omega-3 index; P=.007) which remained significant after adjustment for age, body-mass index, smoking, the ABI and HDL (33%; P=.04). There was also evidence for independent associations between the omega-3 index and IL-6 (P=.001). There were no significant associations between the omega-3 index and vascular function tests. Conclusions In a cohort of patients with PAD, the omega-3 index was inversely associated with biomarkers of inflammation even after adjustment for covariates including the ABI. Because patients with PAD have a high inflammatory burden, further studies should be conducted to determine if manipulation of omega-3 index via dietary changes or fish oil supplementation could improve inflammation and symptoms in these patients. PMID:23830313
Sekhon-Loodu, Satvir; Catalli, Adriana; Kulka, Marianna; Wang, Yanwen; Shahidi, Fereidoon; Rupasinghe, H P Vasantha
Both quercetin glycosides and omega-3 polyunsaturated fatty acids (n-3 PUFA) are well established for their individual health benefits in ameliorating metabolic disease. However, their combined effects are not well documented. It was hypothesized that the beneficial properties of quercetin glycosides can be enhanced when provided in combination with n-3 PUFA. Therefore, the aim of the present study was to investigate the effects of apple flavonols (AF) and fish oil (FO), alone and in combination, on proinflammatory biomarkers and lipid profiles in rats fed a high-fat diet. Sixty male Wistar rats were randomly divided into 5 groups (n = 12) and fed a high-fat diet for 4 weeks. One of the 5 groups of rats was used as the high-fat control. The other 4 groups of rats were injected with lipopolysaccharide (LPS) (5 mg/kg body weight) intraperitoneally, 5 hours before euthanization. One of these 4 groups was used as the hypercholerolemic and inflammatory control (high-fat with lipopolysaccharide [HFL]), and the other 3 received AF (HFL + 25 mg/kg per day AF), FO (HFL + 1 g/kg per day FO), or the combination (HFL + AF + FO). Compared to the HFL group, the AF, FO, and AF + FO groups showed lower serum concentrations of interleukin-6 and C-reactive protein (CRP) levels. The AF, FO, and AF + FO also had lowered serum triacylglycerol and non-high-density lipoprotein cholesterol (HDL-C) concentrations, but higher HDL-C levels relative to the HFL group. An additive effect was observed on serum CRP in the AF + FO group as compared with the AF or FO groups. The results demonstrated that AF and FO inhibited the production of proinflammatory mediators and showed an improved efficacy to lower serum CRP when administered in combination, and they significantly improved blood lipid profiles in rats with diet-induced hyperlipidemia and LPS-induced acute inflammation.
Tikhonenko, Maria; Lydic, Todd A.; Opreanu, Madalina; Li Calzi, Sergio; Bozack, Svetlana; McSorley, Kelly M.; Sochacki, Andrew L.; Faber, Matthew S.; Hazra, Sugata; Duclos, Shane; Guberski, Dennis; Reid, Gavin E.; Grant, Maria B.; Busik, Julia V.
Objective The vasodegenerative phase of diabetic retinopathy is characterized by not only retinal vascular degeneration but also inadequate vascular repair due to compromised bone marrow derived endothelial progenitor cells (EPCs). We propose that n-3 polyunsaturated fatty acid (PUFA) deficiency in diabetes results in activation of the central enzyme of sphingolipid metabolism, acid sphingomyelinase (ASM) and that ASM represents a molecular metabolic link connecting the initial damage in the retina and the dysfunction of EPCs. Research Design and Methods Type 2 diabetic rats on control or docosahexaenoic acid (DHA)-rich diet were studied. The number of acellular capillaries in the retinas was assessed by trypsin digest. mRNA levels of interleukin (IL)-1β, IL-6, intracellular adhesion molecule (ICAM)-1 in the retinas from diabetic animals were compared to controls and ASM protein was assessed by western analysis. EPCs were isolated from blood and bone marrow and their numbers and ability to form colonies in vitro, ASM activity and lipid profiles were determined. Results DHA-rich diet prevented diabetes-induced increase in the number of retinal acellular capillaries and significantly enhanced the life span of type 2 diabetic animals. DHA-rich diet blocked upregulation of ASM and other inflammatory markers in diabetic retina and prevented the increase in ASM activity in EPCs, normalized the numbers of circulating EPCs and improved EPC colony formation. Conclusions In a type 2 diabetes animal model, DHA-rich diet fully prevented retinal vascular pathology through inhibition of ASM in both retina and EPCs, leading to a concomitant suppression of retinal inflammation and correction of EPC number and function. PMID:23383097
Gouveia-Figueira, Sandra; Karlsson, Jessica; Deplano, Alessandro; Hashemian, Sanaz; Svensson, Mona; Fredriksson Sundbom, Marcus; Congiu, Cenzo; Onnis, Valentina; Fowler, Christopher J.
Background Increased endocannabinoid tonus by dual-action fatty acid amide hydrolase (FAAH) and substrate selective cyclooxygenase (COX-2) inhibitors is a promising approach for pain-relief. One such compound with this profile is 2-(2-fluorobiphenyl-4-yl)-N-(3-methylpyridin-2-yl)propanamide (Flu-AM1). These activities are shown by Flu-AM1 racemate, but it is not known whether its two single enantiomers behave differently, as is the case towards COX-2 for the parent flurbiprofen enantiomers. Further, the effects of the compound upon COX-2-derived lipids in intact cells are not known. Methodology/Principal Findings COX inhibition was determined using an oxygraphic method with arachidonic acid and 2-arachidonoylglycerol (2-AG) as substrates. FAAH was assayed in mouse brain homogenates using anandamide (AEA) as substrate. Lipidomic analysis was conducted in unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Both enantiomers inhibited COX-2 in a substrate-selective and time-dependent manner, with IC50 values in the absence of a preincubation phase of: (R)-Flu-AM1, COX-1 (arachidonic acid) 6 μM; COX-2 (arachidonic acid) 20 μM; COX-2 (2-AG) 1 μM; (S)-Flu-AM1, COX-1 (arachidonic acid) 3 μM; COX-2 (arachidonic acid) 10 μM; COX-2 (2-AG) 0.7 μM. The compounds showed no enantiomeric selectivity in their FAAH inhibitory properties. (R)-Flu-AM1 (10 μM) greatly inhibited the production of prostaglandin D2 and E2 in both unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Levels of 2-AG were not affected either by (R)-Flu-AM1 or by 10 μM flurbiprofen, either alone or in combination with the FAAH inhibitor URB597 (1 μM). Conclusions/Significance Both enantiomers of Flu-AM1 are more potent inhibitors of 2-AG compared to arachidonic acid oxygenation by COX-2. Inhibition of COX in lipopolysaccharide + interferon γ- stimulated RAW 264.7 cells is insufficient to affect 2-AG levels despite the
Clayton, E H; Wilkins, J F; Refshauge, G; Friend, M A
Feeding ewes a diet high in n-6 in late gestation can affect fatty acid concentrations in the newborn lamb. The effect of feeding ewes a high n-6 diet prior to conception and in early gestation on lamb n-6 and n-3 status has not previously been examined. The aim of the current study was to determine whether the concentration of n-6 was higher and n-3 was lower in lamb red blood cells (RBC) and plasma when Merino dams were fed a diet high in n-6 either pre-conception only or both pre-conception and in early gestation. Dams were fed a diet low (silage) or high (oats/CSM) in n-6 for either 6 weeks pre-mating only or 6 weeks pre-mating and 17 days post-mating. The fatty acid status of lamb RBC and plasma was determined following birth and compared with dam fatty acids around parturition. The concentration of lamb RBC and plasma n-3 was lower (p < 0.05) when dams received the high n-6 compared with low-n-6 diet around mating, independent of the length of time of feeding. The concentration of n-3 in lamb plasma was also higher when lambs were assessed as being likely rather than unlikely to have suckled prior to blood collection. Lamb RBC and plasma n-3 fatty acids were lower when dams were fed the high compared with the low n-6 diet for only a short time around mating. Transfer of fatty acids via the placenta and milk may account for the differences.
N-Docosahexaenoyl Dopamine, an Endocannabinoid-like Conjugate of Dopamine and the n-3 Fatty Acid Docosahexaenoic Acid, Attenuates Lipopolysaccharide-Induced Activation of Microglia and Macrophages via COX-2.
Wang, Ya; Plastina, Pierluigi; Vincken, Jean-Paul; Jansen, Renate; Balvers, Michiel; Ten Klooster, Jean Paul; Gruppen, Harry; Witkamp, Renger; Meijerink, Jocelijn
Several studies indicate that the n-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) contributes to an attenuated inflammatory status in the development of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. To explain these effects, different mechanisms are being proposed, including those involving endocannabinoids and related signaling molecules. Many of these compounds belong to the fatty acid amides, conjugates of fatty acids with biogenic amines. Conjugates of DHA with ethanolamine or serotonin have previously been shown to possess anti-inflammatory and potentially neuroprotective properties. Here, we synthesized another amine conjugate of DHA, N-docosahexaenoyl dopamine (DHDA), and tested its immune-modulatory properties in both RAW 264.7 macrophages and BV-2 microglial cells. N-Docosahexaenoyl dopamine significantly suppressed the production of nitric oxide (NO), the cytokine interleukin-6 (IL-6), and the chemokines macrophage-inflammatory protein-3α (CCL20) and monocyte chemoattractant protein-1 (MCP-1), whereas its parent compounds, dopamine and DHA, were ineffective. Further exploration of potential effects of DHDA on key inflammatory mediators revealed that cyclooxygenase-2 (COX-2) mRNA level and production of prostaglandin E2 (PGE2) were concentration-dependently inhibited in macrophages. In activated BV-2 cells, PGE2 production was also reduced, without changes in COX-2 mRNA levels. In addition, DHDA did not affect NF-kB activity in a reporter cell line. Finally, the immune-modulatory activities of DHDA were compared with those of N-arachidonoyl dopamine (NADA) and similar potencies were found in both cell types. Taken together, our data suggest that DHDA, a potentially endogenous endocannabinoid, may be an additional member of the group of immune-modulating n-3 fatty acid-derived lipid mediators.
Hepatic storage and transport of n-3 and n-6 polyunsaturated fatty acids by very-low-density lipoproteins in growing rats fed low- or adequate-protein diets with sunflower, soybean, coconut, and salmon oils.
Bouziane, M; Belleville, J; Prost, J
Protein and essential fatty acid (EFA) deficiencies may both occur in chronic malnutrition and have common symptoms. To determine the interactions between dietary protein intake and EFA availability, rats were fed purified diets containing 20% or 2% casein and 5% as one of four fats (sunflower, soybean, coconut, or salmon oil) that differed particularly in their n-6 and n-3 polyunsaturated fatty acids (PUFAs). Protein malnutrition enhanced hepatic triacylglycerol and cholesterol concentrations while decreasing hepatic protein and phospholipid contents and mass and components of very-low-density lipoprotein (VLDL). The ratio of PUFAs to saturated fatty acids (SFAs) was consistently depressed by protein malnutrition in liver and VLDL triacylglycerol and phospholipid. Total n-6 and n-3 fatty acids were diminished by protein malnutrition, except with salmon oil, with which a decrease in 20:5n-3 was compensated for by an increase in 22:6n-3. The ratio of 20:4n-6 to 18:2n-6 was enhanced in liver phospholipid and VLDL triacylglycerol, and modified little in liver triacylglycerol. Generally, the ratio of 20:3n-9 to 20:4n-6, an index for EFA deficiency, was raised with protein malnutrition in liver triacylglycerol and phospholipid and in VLDL triacylglycerol. The extent of changes in each fatty acid proportion varied according to the oil fed. Overall, VLDL-apolipoprotein concentrations were, in general, strongly reduced with protein malnutrition. In conclusion, protein malnutrition may accelerate marginal EFA deficiency and decrease long-chain PUFA bioavailability and thus increase EFA requirement.
Exposure to a maternal n-3 fatty acid-deficient diet during brain development provokes excessive hypothalamic-pituitary-adrenal axis responses to stress and behavioral indices of depression and anxiety in male rat offspring later in life.
Chen, Hui-Feng; Su, Hui-Min
Brain docosahexaenoic acid (DHA, 22:6n-3) accumulates rapidly during brain development and is essential for normal neurological function. The aim of this study was to evaluate whether brain development was the critical period in which DHA deficiency leads to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress later in life. Rats were exposed to an n-3 fatty acid-deficient diet or the same diet supplemented with fish oil as an n-3 fatty acid-adequate diet either throughout the preweaning period from embryo to weaning at 3 weeks old or during the postweaning period from 3 to 10 weeks old. Exposure to the n-3 fatty acid-deficient diet during the preweaning period resulted, at weaning, in a significant decrease in hypothalamic DHA levels and a reduced male offspring body weight. DHA deficiency during the preweaning period significantly increased and prolonged restraint stress-induced changes in colonic temperature and serum corticosterone levels, caused a significant increase in GABA(A) antagonist-induced heart rate changes and enhanced depressive-like behavior in the forced swimming test and anxiety-like behavior in the plus-maze test in later life. These effects were not seen in male rats fed the n-3 fatty acid-deficient diet during the postweaning period. These results suggest that brain development is the critical period in which DHA deficiency leads to excessive HPA responses to stress and elevated behavioral indices of depression and anxiety in adulthood. We propose that these effects of hypothalamic DHA deficiency during brain development may involve a GABA(A) receptor-mediated mechanism.
Scislowski, V; Bauchart, D; Gruffat, D; Laplaud, P M; Durand, D
Two experiments were conducted using crossbred Salers x Charolais fattening steers fed diets enriched with no supplemental oilseeds or oils rich in either n-6 PUFA (from sunflower seeds) or n-3 PUFA (from linseeds) provided either as seeds incorporated in the diet (i.e., not protected from ruminal bacterial hydrogenation) or by chronic infusion into the duodenum (protected form). In the Sunflower experiment, animals (initial age = 454 +/- 20 d; initial BW = 528 +/- 36 kg) received a control diet for 70 d (CS, n = six) consisting of hay and concentrate, or the same basal diet supplemented with sunflower oil (4% of dietary DM), either fed as seeds (SS, n = six) or infused into the duodenum (ISO, n = six). The same experimental design was applied to animals (initial age = 412 +/- 33 d; initial BW = 536 +/- 33 kg) used in the Linseed experiment (CL, LS, and ILO; n = 8 per group). For all animals, blood was sampled every 15 d during 70 d. In both trials, a significant diet x time interaction (P < 0.001) was detected for plasma concentrations of apolipoprotein A-I, phospholipids, and free and esterified cholesterol, with values increasing with time during administration of the PUFA-rich diets being more evident with ISO and ILO diets. Plasma fatty acids were altered with oil infusions, with increased concentrations of n-6 (1.6-fold; P < 0.05) and n-3 PUFA (4.5-fold; P < 0.05) and of their respective indicies of peroxidizability (1.2- and 1.5-fold with Diets ISO and ILO, respectively; P < 0.05). In vitro copper-induced peroxidation of lipids revealed a decreased length of the lag phase in the process of conjugated diene generation by 48% (P < 0.005) with the ILO diet, indicating less resistance against peroxidation than in control steers. Compared with CS, the ISO treatment increased plasma alpha-tocopherol (x2.5; P < 0.05) leading to similar resistance against peroxidation. After depletion of this vitamin, the rates of peroxidation and production of conjugated dienes
... other health conditions > Fatty acid oxidation disorders Fatty acid oxidation disorders E-mail to a friend Please ... these disorders, go to genetests.org . What fatty acid oxidation disorders are tested for in newborn screening? ...
Londero, Lisiane G; Rieger, Débora K; Hansen, Fernanda; Silveira, Simone L; Martins, Tiago L; Lulhier, Francisco; da Silva, Roselis S; Souza, Diogo O; Perry, Marcos L S; de Assis, Adriano M
Long-chain polyunsaturated n-3 fatty acids (n-3 LCPUFAs) have hypolipidemic effects and modulate intermediary metabolism to prevent or reverse insulin resistance in a way that is not completely elucidated. Here, effects of these fatty acids on the lipid profile, phosphoenolpyruvate carboxykinase (PEPCK) activity, lipid synthesis from glucose in epididymal adipose tissue (Ep-AT) and liver were investigated. Male rats were fed a high-sucrose diet (SU diet), containing either sunflower oil or a mixture of sunflower and fish oil (SU-FO diet), and the control group was fed a standard diet. After 13 weeks, liver, adipose tissue and blood were harvested and analysed. The dietary n-3 LCPUFAs prevented sucrose-induced increase in adiposity and serum free fat acids, serum and hepatic triacylglycerol and insulin levels. Furthermore, these n-3 LCPUFAs decreased lipid synthesis from glucose and increased PEPCK activity in the Ep-AT of rats fed the SU-FO diet compared to those fed the SU diet, besides reducing lipid synthesis from glucose in hepatic tissue. Thus, the inclusion of n-3 LCPUFAs in the diet may be beneficial for the prevention or attenuation of dyslipidemia and insulin resistance, and for reducing the risk of related chronic diseases.
Khoshvaght, Ali; Towhidi, Armin; Zare-shahneh, Ahmad; Noruozi, Mohammad; Zhandi, Mahdi; Davachi, Navid Dadashpour; Karimi, Reza
The goal of this study was to investigate the effect of fish oil-supplemented diet on fresh and post-thaw semen quality and sperm lipid composition in bulls. Bulls were randomly assigned to two groups (n = 6). Six bulls were used as the control group and six received the fish oil (1.2% dry matter of total diet) for 11 weeks. Semen was individually collected from each bull and frozen biweekly. Semen volume, sperm concentration, viability, progressive motility, and fatty acid profile of sperm were measured in 1st, 3rd, 5th, 7th, 9th, and 11th week of experiment. Viability, progressive motility, and fatty acid profile of post-thaw sperm were also measured in 3rd, 5th, 9th, and 11th week of experiment. Data were analyzed with using Proc GLM or MIXED (for repeated measurement data) in SAS program. The fish oil-supplemented diet increased the semen volume and sperm concentration. The fish oil-supplemented diet also altered the viability, progressive motility, and fatty acid profile of fresh and post-thaw sperm. In conclusion, feeding a fish oil-enriched diet via alteration of fatty acid profile of sperm lipid could improve in vitro quality of fresh and post-thaw sperm in Holstein bulls.
Mazzuco, H; McMurtry, J P; Kuo, A Y; Hester, P Y
This study investigated changes in bone integrity and circulating concentrations of insulin-like growth factor-I (IGF-I) of hens subjected to 2 distinct molting regimens and fed pre- and postmolt diets high in n-3 or n-6 fatty acids. A dual-energy x-ray absorptiometer determined bone mineral density (BMD) of the tibia and humerus of 45 live hens from 62 to 76 wk of age. Densitometric scans were also conducted in excised tibia and humerus at 66, 71, and 76 wk of age. Concentrations of IGF-I were monitored using an homologous RIA at the same ages. The molting treatments consisted of 10 d of fasting + cracked corn for 7 d + pullet developer diet for 10 d or a nonfasting molt (wheat-middlings-based diet for 27 d). Five weeks prior to and after either molt treatment, birds were fed 1 of 2 diets containing dietary n-6/ n-3 fatty acids ratios of 0.6 or 8.0. At the end of the molt (71 wk of age), tibial BMD decreased 30% in fasted and 11% in nonfasted molt regimens, and the fatty acid content of the premolt diet had no effect on the decline in BMD. The BMD of the humerus also decreased during molt with the exception of hens subjected to a nonfasted molt and fed n-3 fatty acid diets in which their BMD values were similar to or greater (at 73 wk of age) than those of controls during the entire experimental period (treatment by bone by age, P < or = 0.0001). Induced molt affected circulating IGF-I concentrations (treatment by age interaction, P < or = 0.0001), and the response was the same regardless of molt regimen (fasting vs. nonfasting) or diet (n-3 vs. n-6 fatty acids). A decrease in IGF-I 54 h postmolt was noted; however, from 13 to 43 d postmolt, all molted birds had elevated IGF-I as compared with controls. In conclusion, a nonfasted molt as compared with fasted molt was less detrimental to bone mineralization; dietary n-6/n-3 fatty acid ratios in the pre- and postmolt diets had little effect on the decline of skeletal integrity during molt, and circulating IGF
Juárez-Hernández, Eva; Chávez-Tapia, Norberto C; Uribe, Misael; Barbero-Becerra, Varenka J
Nonalcoholic fatty liver disease (NAFLD) is characterized by fat deposition in hepatocytes, and a strong association with nutritional factors. Dietary fatty acids are classified according to their biochemical properties, which confer their bioactive roles. Monounsaturated fatty acids have a dual role in various human and murine models. In contrast, polyunsaturated fatty acids exhibit antiobesity, anti steatosic and anti-inflammatory effects. The combination of these forms of fatty acids-according to dietary type, daily intake and the proportion of n-6 to n-3 fats-can compromise hepatic lipid metabolism. A chemosensory rather than a nutritional role makes bioactive fatty acids possible biomarkers for NAFLD. Bioactive fatty acids provide health benefits through modification of fatty acid composition and modulating the activity of liver cells during liver fibrosis. More and better evidence is necessary to elucidate the role of bioactive fatty acids in nutritional and clinical treatment strategies for patients with NAFLD.
While considerable research has centered upon the role of linoleic acid (LNA; 18:2n6) as a competitive inhibitor of alpha-linolenic (ALA; 18:3n3) metabolism, a growing literature indicates that the amount of fat consumed can reduce the elongation and desaturation process. However, little data exist ...
Heerwagen, Margaret J R; Stewart, Michael S; de la Houssaye, Becky A; Janssen, Rachel C; Friedman, Jacob E
Maternal and pediatric obesity has risen dramatically over recent years, and is a known predictor of adverse long-term metabolic outcomes in offspring. However, which particular aspects of obese pregnancy promote such outcomes is less clear. While maternal obesity increases both maternal and placental inflammation, it is still unknown whether this is a dominant mechanism in fetal metabolic programming. In this study, we utilized the Fat-1 transgenic mouse to test whether increasing the maternal n-3/n-6 tissue fatty acid ratio could reduce the consequences of maternal obesity-associated inflammation and thereby mitigate downstream developmental programming. Eight-week-old WT or hemizygous Fat-1 C57BL/6J female mice were placed on a high-fat diet (HFD) or control diet (CD) for 8 weeks prior to mating with WT chow-fed males. Only WT offspring from Fat-1 mothers were analyzed. WT-HFD mothers demonstrated increased markers of infiltrating adipose tissue macrophages (P<0.02), and a striking increase in 12 serum pro-inflammatory cytokines (P<0.05), while Fat1-HFD mothers remained similar to WT-CD mothers, despite equal weight gain. E18.5 Fetuses from WT-HFD mothers had larger placentas (P<0.02), as well as increased placenta and fetal liver TG deposition (P<0.01 and P<0.02, respectively) and increased placental LPL TG-hydrolase activity (P<0.02), which correlated with degree of maternal insulin resistance (r = 0.59, P<0.02). The placentas and fetal livers from Fat1-HFD mothers were protected from this excess placental growth and fetal-placental lipid deposition. Importantly, maternal protection from excess inflammation corresponded with improved metabolic outcomes in adult WT offspring. While the offspring from WT-HFD mothers weaned onto CD demonstrated increased weight gain (P<0.05), body and liver fat (P<0.05 and P<0.001, respectively), and whole body insulin resistance (P<0.05), these were prevented in WT offspring from Fat1-HFD mothers. Our results suggest that
Dietary Buglossoides Arvensis Oil Increases Circulating n-3 Polyunsaturated Fatty Acids in a Dose-Dependent Manner and Enhances Lipopolysaccharide-Stimulated Whole Blood Interleukin-10—A Randomized Placebo-Controlled Trial
Lefort, Natalie; LeBlanc, Rémi; Surette, Marc E.
Buglossoides arvensis (Ahiflower) oil is a dietary oil rich in stearidonic acid (20% SDA; 18:4 n-3). The present randomized, double blind, placebo-controlled clinical trial investigated the effects of three Ahiflower oil dosages on omega-3 polyunsaturated fatty acid (PUFA) content of plasma and mononuclear cells (MCs) and of the highest Ahiflower dosage on stimulated cytokine production in blood. Healthy subjects (n = 88) consumed 9.7 mL per day for 28 days of 100% high oleic sunflower oil (HOSO); 30% Ahiflower oil (Ahi) + 70% HOSO; 60% Ahi + 40% HOSO; and 100% Ahi. No clinically significant changes in blood and urine chemistries, blood lipid profiles, hepatic and renal function tests nor hematology were measured. Linear mixed models (repeated measures design) probed for differences in time, and time × treatment interactions. Amongst significant changes, plasma and MC eicosapentaenoic acid (EPA, 20:5 n-3) levels increased from baseline at day 28 in all Ahiflower groups (p < 0.05) and the increase was greater in all Ahiflower groups compared to the HOSO control (time × treatment interactions; p < 0.05). Similar results were obtained for α-linolenic acid (ALA, 18:3 n-3), eicosatetraenoic acid (ETA, 20:4 n-3), and docosapentaenoic acid (DPA, 22:5 n-3) content; but not docosahexaenoic acid (DHA, 22:6 n-3). Production of interleukin-10 (IL-10) was increased in the 100% Ahiflower oil group compared to 100% HOSO group (p < 0.05). IL-10 production was also increased in lipopolysaccharide (LPS)-stimulated M2-differentiated THP-1 macrophage-like cells in the presence of 20:4 n-3 or EPA (p < 0.05). Overall; this indicates that the consumption of Ahiflower oil is associated with an anti-inflammatory phenotype in healthy subjects. PMID:28287415
Omega-3/('-3) or n-3 fatty acids are a family of unsaturated fatty acids that have in common a final carbon-carbon double bond in the n-3 position. n-3 Fatty acids which are important in human nutrition are: a-linolenic acid (18:3, n-3; ALA), eicosapentaenoic acid (20:5, n-3; EPA), and docosahexaen...
Somerville, Chris; Broun, Pierre; van de Loo, Frank
This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fatty acids in transgenic plants. In addition, the use of genes encoding fatty acid hydroxylases or desaturases to alter the level of lipid fatty acid unsaturation in transgenic plants is described.
Lopez-Jimena, Benjamin; Lyons, Philip; Herath, Tharangani; Richards, Randolph H; Leaver, Michael; Bell, J Gordon; Adams, Alexandra; Thompson, Kim D
Salmon pancreas disease (SPD) is one of the most commercially significant viral diseases of farmed Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) in Europe. In this study, the potential for dietary mitigation of the disease using different polyunsaturated fatty acid (PUFA) profiles was assessed in rainbow trout. We experimentally infected fish with salmonid alphavirus subtype 1 (SAV-1), the causative agent of SPD. These fish were fed two diets with different n-3/n-6 PUFA ratio (high omega 3, 3.08, and high omega 6, 0.87). We assessed the influence of the diets on the fatty acid composition of the heart at 0 days post infection (d.p.i.) (after 4 weeks of feeding the experimental diets prior to SAV-1 infection), and sampled infected and control fish at 5, 15 and 30d.p.i. Viral E1 and E2 glycoprotein genes were quantified by two absolute real-time PCRs in all the organs sampled, and significantly lower levels of the virus were evident in the organs of fish fed with high omega 6. Characteristic pathological lesions were identified in infected fish as early as 5d.p.i., with no significant differences in the pathology lesion scores between the two dietary regimes. This study shows that decreasing the n-3/n-6 PUFA ratio in experimental diets of rainbow trout changes the fatty acid content of the fish, and is associated with reduced SAV-1 replication in rainbow trout.
Fearon, K C H; von Meyenfeldt, M F; Moses, A G W; van Geenen, R; Roy, A; Gouma, D J; Giacosa, A; Van Gossum, A; Bauer, J; Barber, M D; Aaronson, N K; Voss, A C; Tisdale, M J
Aim: N-3 fatty acids, especially eicosapentaenoic acid (EPA), may possess anticachectic properties. This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants (experimental: E) with an isocaloric isonitrogenous control supplement (C) for their effects on weight, lean body mass (LBM), dietary intake, and quality of life in cachectic patients with advanced pancreatic cancer. Methods: A total of 200 patients (95 E; 105 C) were randomised to consume two cans/day of the E or C supplement (480 ml, 620 kcal, 32 g protein ± 2.2 g EPA) for eight weeks in a multicentre, randomised, double blind trial. Results: At enrolment, patients’ mean rate of weight loss was 3.3 kg/month. Intake of the supplements (E or C) was below the recommended dose (2 cans/day) and averaged 1.4 cans/day. Over eight weeks, patients in both groups stopped losing weight (Δ weight E: −0.25 kg/month versus C: −0.37 kg/month; p = 0.74) and LBM (Δ LBM E: +0.27 kg/month versus C: +0.12 kg/month; p = 0.88) to an equal degree (change from baseline E and C, p<0.001). In view of evident non-compliance in both E and C groups, correlation analyses were undertaken to examine for potential dose-response relationships. E patients demonstrated significant correlations between their supplement intake and weight gain (r = 0.50, p<0.001) and increase in LBM (r = 0.33, p = 0.036). Such correlations were not statistically significant in C patients. The relationship of supplement intake with change in LBM was significantly different between E and C patients (p = 0.043). Increased plasma EPA levels in the E group were associated with weight and LBM gain (r = 0.50, p<0.001; r = 0.51, p = 0.001). Weight gain was associated with improved quality of life (p<0.01) only in the E group. Conclusion: Intention to treat group comparisons indicated that at the mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were
Patten, Glen S; Sanguansri, Luz; Augustin, Mary Ann; Abeywardena, Mahinda Y; Bird, Anthony R; Patch, Craig S; Belobrajdic, Damien P
Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) may be more bioavailable from krill oil compared to fish oil due to their phospholipid structure. We tested whether a microencapsulated krill and tuna oil blend (ME-TOKO) provided greater LC n-3 PUFA bioavailability, improved blood lipid profiles and increased intestinal contractility compared to microencapsulated tuna oil (ME-TO). Rats were divided into three groups to receive isocaloric diets containing ME-TO, ME-TOKO and microencapsulated olive oil (ME-OO) at 0.3 or 2 g/100 g for 4 weeks. Final body and organ weights, feed intake and waste output were similar. ME-TOKO rats had higher plasma total LC n-3 PUFA levels compared to ME-TO, but liver LC n-3 PUFA levels and plasma triglyceride and cholesterol levels were similar in non-fasted rats. Diets containing 2% ME-TO and ME-TOKO also showed similar increases in ileal contractility. In summary, ME-TO bioavailability of LC n-3 PUFA was similar to ME-TOKO.
Watson, Aaron M; Barrows, Frederic T; Place, Allen R
We examined growth performance and the lipid content in juvenile cobia, Rachycentron canadum, fed a taurine supplemented (1.5 %), plant protein based diet with two fish oil replacements. The first fish oil replacement was a thraustochytrid meal (TM + SOY) plus soybean oil (~9 % CL) and the second was a canola oil supplemented with the essential fatty acids (EFA) docosahexaenoic acid (DHA) and arachidonic acid (ARA) (~8 % CL). The diet using the thraustochytrid meal plus soybean oil performed equivalently to the fish oil diet; both resulting in significantly higher growth rates, lower feed conversion ratios, and higher survival than the supplemented canola oil diet, even though all three diets were similar in overall energy and met known protein and lipid requirements for cobia. The poor performance of the canola oil diet was attributed to insufficient addition of EFA in the supplemented canola oil source. Increasing levels of EFA in the supplemented canola oil above 0.5 g EFA kg(-1) would likely improve results with cobia. When fish fed either of the fish oil replacement diets were switched to the fish oil control diet, fatty acid profiles of the fillets were observed to transition toward that of the fish oil diet and could be predicted based on a standard dilution model. Based on these findings, a formulated diet for cobia can be produced without fish products providing 100 % survivorship, specific growth rates greater than 2.45 and feed conversion ratios less than 1.5, as long as taurine is added and EFA levels are above 0.5 g EFA kg(-1).
Elmaleh, David R.; Livni, Eli
In one aspect, a radioactively labeled analog of a fatty acid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fatty acid.
OBJECTIVE To examine evidence for the role of omega-3 fatty acids in cardiovascular disease. QUALITY OF EVIDENCE PubMed was searched for articles on the role of omega-3 fatty acids in cardiovascular disease. Level I and II evidence indicates that omega-3 fatty acids are beneficial in improving cardiovascular outcomes. MAIN MESSAGE Dietary intake of omega-3 fatty acids has declined by 80% during the last 100 years, while intake of omega-6 fatty acids has greatly increased. Omega-3 fatty acids are cardioprotective mainly due to beneficial effects on arrhythmias, atherosclerosis, inflammation, and thrombosis. There is also evidence that they improve endothelial function, lower blood pressure, and significantly lower triglycerides. CONCLUSION There is good evidence in the literature that increasing intake of omega-3 fatty acids improves cardiac outcomes. Physicians need to integrate dietary recommendations for consumption of omega-3 fatty acids into their usual cardiovascular care. PMID:16812965
Omega-6 fatty acids are types of fats. Some types are found in vegetable oils, including corn, evening primrose seed, safflower, and soybean oils. Other types of omega-6 fatty acids are found in black currant seed, borage seed, ...
Experimental studies have shown that omega-6 fatty acids enhance and omega - 3 fatty acids suppress oncogenesis. Correlational studies also indicate...that breast cancer incidence is positively linked to omega-6 consumption but is negatively related to intake of omega - 3 fatty acids, derived mainly from...arachidonic acid), and omega - 3 fatty acids (20:5n3, eicosapentaenoic acid; 22:6n-3, docosahexaenoic acid) were similar in cases and controls
Chicco, Adriana; Creus, Agustina; Illesca, Paola; Hein, Gustavo Juan; Rodriguez, Silvia; Fortino, Alejandra
The interaction between fetal programming and the post-natal environment suggests that the post-natal diet could amplify or attenuate programmed outcomes. We investigated whether dietary n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) at weaning resulted in an amelioration of dyslipidemia, adiposity and liver steatosis that was induced by a sucrose-rich diet (SRD; where the fat source is corn oil) from the onset of pregnancy up to adulthood. During pregnancy and lactation, dams were fed an SRD or the standard powdered rodent commercial diet (RD). At weaning and until 150 days of life, male offspring from SRD-dams were divided into two groups and fed an SRD or SRD-with-fish oil [where 6% of the corn oil was partially replaced by fish oil (FO) 5% and corn oil (CO) 1%], forming SRD-SRD or SRD-FO groups. Male offspring from RD-dams continued with RD up to the end of the experimental period, forming an RD-RD group. The presence of FO in the weaning diet showed the following: prevention of hypertriglyceridemia and liver steatosis, together with increased lipogenic enzyme activity caused by a maternal SRD; the complete normalization of CPT I activity and PPARα protein mass levels; a slight but not statistically significant accretion of visceral adiposity; and limited body fat content and reduced plasma free fatty acid levels. All of these results were observed even in the presence of a high-sucrose diet challenge after weaning. SRD-dams' breast milk showed a more saturated fatty acid composition. These results suggest the capacity of n-3 PUFAs to overcome some adverse outcomes induced by a maternal and post-weaning sucrose-rich diet.
Calder, P C; Yaqoob, P; Thies, F; Wallace, F A; Miles, E A
The immune system acts to protect the host against pathogenic invaders. However, components of the immune system can become dysregulated such that their activities are directed against host tissues, so causing damage. Lymphocytes are involved in both the beneficial and detrimental effects of the immune system. Both the level of fat and the types of fatty acid present in the diet can affect lymphocyte functions. The fatty acid composition of lymphocytes, and other immune cells, is altered according to the fatty acid composition of the diet and this alters the capacity of those cells to produce eicosanoids, such as prostaglandin E2, which are involved in immunoregulation. A high fat diet can impair lymphocyte function. Cell culture and animal feeding studies indicate that oleic, linoleic, conjugated linoleic, gamma-linolenic, dihomo-gamma-linolenic, arachidonic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acids can all influence lymphocyte proliferation, the production of cytokines by lymphocytes, and natural killer cell activity. High intakes of some of these fatty acids are necessary to induce these effects. Among these fatty acids the long chain n-3 fatty acids, especially eicosapentaenoic acid, appear to be the most potent when included in the human diet. Although not all studies agree, it appears that fish oil, which contains eicosapentaenoic acid, down regulates the T-helper 1-type response which is associated with chronic inflammatory disease. There is evidence for beneficial effects of fish oil in such diseases; this evidence is strongest for rheumatoid arthritis. Since n-3 fatty acids also antagonise the production of inflammatory eicosanoid mediators from arachidonic acid, there is potential for benefit in asthma and related diseases. Recent evidence indicates that fish oil may be of benefit in some asthmatics but not others.
Monk, Jennifer M; Liddle, Danyelle M; Cohen, Daniel J A; Tsang, Denis H; Hillyer, Lyn M; Abdelmagid, Salma A; Nakamura, Manabu T; Power, Krista A; Ma, David W L; Robinson, Lindsay E
Typically fatty acids (FA) exert differential immunomodulatory effects with n-3 [α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and n-6 [linoleic acid (LA) and arachidonic acid (AA)] exerting anti- and pro-inflammatory effects, respectively. This over-simplified interpretation is confounded by a failure to account for conversion of the parent FA (LA and ALA) to longer-chain bioactive products (AA and EPA/DHA, respectively), thereby precluding discernment of the immunomodulatory potential of specific FA. Therefore, we utilized the Δ6-desaturase model, wherein knockout mice (D6KO) lack the Fads2 gene encoding for the rate-limiting enzyme that initiates FA metabolism, thereby providing a model to determine specific FA immunomodulatory effects. Wild-type (WT) and D6KO mice were fed one of four isocaloric diets differing in FA source (9weeks): corn oil (LA-enriched), arachidonic acid single cell oil (AA-enriched), flaxseed oil (ALA-enriched) or menhaden fish oil (EPA/DHA-enriched). Splenic mononuclear cell cytokine production in response to lipopolysaccharide (LPS), T-cell receptor (TCR) and anti-CD40 stimulation was determined. Following LPS stimulation, AA was more bioactive compared to LA, by increasing inflammatory cytokine production of IL-6 (1.2-fold) and TNFα (1.3-fold). Further, LPS-stimulated IFNγ production in LA-fed D6KO mice was reduced 5-fold compared to LA-fed WT mice, indicating that conversion of LA to AA was necessary for cytokine production. Conversely, ALA exerted an independent immunomodulatory effect from EPA/DHA and all n-3 FA increased LPS-stimulated IL-10 production versus LA and AA. These data definitively identify specific immunomodulatory effects of individual FA and challenge the simplified view of the immunomodulatory effects of n-3 and n-6 FA.
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
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
The consumption of n-3 polyunsaturated fatty acids differentially modulates gene expression of peroxisome proliferator-activated receptor alpha and gamma and hypoxia-inducible factor 1 alpha in subcutaneous adipose tissue of obese adolescents.
Mejía-Barradas, César M; Del-Río-Navarro, Blanca E; Domínguez-López, Aarón; Campos-Rodríguez, Rafael; Martínez-Godínez, María de-Los-Á; Rojas-Hernández, Saúl; Lara-Padilla, Eleazar; Abarca-Rojano, Edgar; Miliar-García, Ángel
The aim of this study was to evaluate the effect of long-chain omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on metabolic state and gene expression in subcutaneous adipose tissues of obese adolescents. Obese adolescents (n = 26, 10 girls and 16 boys) aged 12.4 ± 2.1 years were assigned to a 12-week regimen of n-3 PUFA intake. Five times per day, subjects received a food supplement consisting of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (3 g per day, 944 mg EPA, and 2,088 mg DHA). Blood parameters were measured, and subcutaneous adipose tissue biopsies were analyzed to determine gene expression at baseline and after 12 weeks. Student's t test and the Wilcoxon signed-rank test were used to estimate differences in arithmetic means of pre- and post-dietary supplementation for various anthropometric, biochemical, clinical, and gene expression parameters. After 12 weeks, n-3 PUFA consumption was associated with decreased body mass index (29.7 ± 4.6 vs. 27.8 ± 4.4 kg/m(2); P < 0.001), waist circumference (93.2 ± 9.9 vs. 90.5 ± 10.0 cm; P < 0.003), hip circumference (102.9 ± 10.9 vs. 101.1 ± 10.9 cm; P < 0.014), and blood triglyceride levels (220.8 ± 27.4 vs. 99.7 ± 32.7 mg/dL; P < 0.001). Fatty acid supplementation/n3 PUFA supplementation was associated with a downregulated expression of the genes encoding PPARγ and PGC-1α (P < 0.001), and an upregulated expression of the genes encoding PPARα (P < 0.007) and SREBP1 (P < 0.021). The expressions of SOD2 (P < 0.04), CAT (P < 0.001), GPX3 (P < 0.032) and HIF-1α protein also decreased. Our study demonstrated that n-3 PUFA consumption and dietary restriction improved the anthropometric parameters and decreased the triglycerides levels of the adolescents, suggesting a reduction in hypoxia in subcutaneous adipose tissue.
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...
Fan, Chaonan; Sun, Wenfei; Fu, Huicong; Dong, Hua; Xia, Lulu; Lu, Yuanyuan; Deckelbaum, Richard J; Qi, Kemin
Objetivo: a pesar de que los ácidos grasos poliinsaturados n-3 (PUFAs por sus siglas en inglés) desempeñan un papel fundamental en el desarrollo y en las funciones cerebrales, aún no está bien definido el nivel óptimo de PUFAs n-3 ni la ratio óptima de PUFA n-6/n-3 en la dieta materna. En este estudio hemos investigado los efectos de las ratios nutricionales de PUFA n-6/n-3 durante la gestación sobre la neurogénesis y la apoptosis en el cerebro de crías de ratón. Métodos: se alimentó a hembras de ratón C57BL/6J con una de las tres dietas de estudio: ratio alta, media y baja de PUFA n-6/n-3 (15,7:1, 6,3:1, 1,6:1). También se añadió una dieta rica en aceite de pescado con una ratio n-6/n-3 de 1:5,7; como control se empleó una dieta deficitaria en PUFA n-3. Los regímenes alimenticios se iniciaron dos meses antes de la concepción de los ratones y continuó durante todo el embarazo. Se detectó la neurogénesis y apoptosis del área hipocampal CA3 en las crías. Resultados: en comparación con la dieta deficitaria en PUFA n-3, las dietas con PUFA que contienen n-3, particularmente aquellas con ratios PUFA n-6/n-3 de 6,3:1 y 1,6:1, aumentaron significativamente la fosforilación de histona H3 en la Ser10 (p-H3ser10) y las células calretinina positivas en el área hipocampal CA3 de las crías. Además, se detectó un aumento de la expresión de proteína Bcl2, una reducción de la expresión de proteína Bax, y una reducción de la actividad de caspasa 3, así como de las cifras de células apoptósicas TUNEL en las tres dietas, con ratios altas, medias y bajas de PUFA n-6/n-3. Sin embargo, no se observó diferencias en ninguno de estos parámetros entre el grupo de dieta rica en aceite de pescado y el grupo de dieta deficitaria en PUFA n-3. Conclusiones: estos datos sugieren que una ingesta más elevada de PUFA n-3 con una ratio más baja de PUFAs n-6/n-3 entre 6:1 y 1:1 aproximadamente, administrada a las madres durante la gestación, podría ser
Efficacy of n-3 polyunsaturated fatty acids and feasibility of optimizing preventive strategies in patients at high cardiovascular risk: rationale, design and baseline characteristics of the Rischio and Prevenzione study, a large randomised trial in general practice
Background The optimization of preventive strategies in patients at high risk of cardiovascular events and the evaluation of bottlenecks and limitations of transferring current guidelines to the real world of clinical practice are important limiting steps to cardiovascular prevention. Treatment with n-3 polyunsaturated fatty acids improves prognosis after myocardial infarction, but evidence of this benefit is lacking in patients at high cardiovascular risk, but without a history of myocardial infarction. Methods/design Patients were eligible if their general practitioner (GP) considered them at high cardiovascular risk because of a cardiovascular disease other than myocardial infarction, or multiple risk factors (at least four major risk factors in non-diabetic patients and one in diabetics). Patients were randomly allocated to treatment with n-3 polyunsaturated fatty acids (1 g daily) or placebo in a double-blind study and followed up for five years by their GPs to assess the efficacy of the treatment in preventing cardiovascular mortality (including sudden death) and hospitalization for cardiovascular reasons. The secondary, epidemiological, aim of the study is to assess whether it is feasible to adopt current guidelines in everyday clinical practice, with a view to optimizing all the available preventive strategies in people at high cardiovascular risk. A nation-wide network of 860 GPs admitted 12,513 patients to the study between February 2004 and March 2007. The mean age was 64 years and 62% were males. Diabetes mellitus plus one or more cardiovascular risk factors was the main inclusion criterion (47%). About 30% of patients were included because of a history of atherosclerotic cardiovascular disease, 21% for four or more risk factors, and less than 1% for other reasons. Discussion The Rischio and Prevenzione (R&P) project provides a feasible model to test the efficacy of n-3 polyunsaturated fatty acid therapy in patients at high cardiovascular risk with no
Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to new compounds, 7,10-dihydroxy-8(E)-octadecen...
Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compounds, 7,10-dihydroxy-8(E)-octad...
Effects of dietary n-3 highly unsaturated fatty acids on growth, nonspecific immunity, expression of some immune related genes and disease resistance of large yellow croaker (Larmichthys crocea) following natural infestation of parasites (Cryptocaryon irritans).
Zuo, Rantao; Ai, Qinghui; Mai, Kangsen; Xu, Wei; Wang, Jun; Xu, Houguo; Liufu, Zhiguo; Zhang, Yanjiao
The study was conducted to investigate the effects of dietary n-3 highly unsaturated fatty acid (n-3 HUFA) on growth, nonspecific immunity, expression of some immune related genes and disease resistance of juvenile large yellow croaker (Larmichthys crocea) following natural infestation of parasites (Cryptocaryon irritans). Six isoproteic and isolipidic diets were formulated with graded levels of n-3 HUFA ranging from 0.15% to 2.25% of the dry weight and the DHA/EPA was approximately fixed at 2.0. Each diet was randomly allocated to triplicate groups of fish in floating sea cages (1.0 × 1.0 × 1.5 m), and each cage was stocked with 60 fish (initial average weight 9.79 ± 0.6 g). Fish were fed twice daily (05:00 and 17:00) to apparent satiation for 58 days. Results showed that moderate n-3 HUFA level (0.98%) significantly enhanced growth compared with the control group (0.15% HUFA) (P < 0.05), while higher n-3 HUFA levels (1.37%, 1.79% and 2.25%) had detrimental effects on the growth though no significance was found (P > 0.05). Nitro blue tetrazolium (NBT) positive leucocytes percentage of head kidney and serum superoxide dismutase (SOD) activity increased with increasing n-3 HUFA from 0.15% to 0.60%, and decreased with further increase of n-3 HUFA from 0.60% to 2.25% (P < 0.05). Serum lysozyme activity increased significantly as n-3 HUFA increased from 0.15% to 1.37%, and then decreased with n-3 HUFA from 1.37% to 2.25% (P > 0.05). There were no significant differences in phagocytosis index (PI) of head kidney leucocytes among dietary treatments (P > 0.05). The hepatic mRNA expression of Toll-like receptor 22 (TLR22) and Myeloid differentiation factor 88 (MyD88) was significantly up-regulated in fish fed the diets with low or moderate levels, while in kidney this increment was only found at specific sampling time during the natural infestation of parasites. The 13 d cumulative mortality rate following natural infestation of parasites decreased
N-3 Polyunsaturated Fatty Acids Improve Liver Lipid Oxidation-Related Enzyme Levels and Increased the Peroxisome Proliferator-Activated Receptor α Expression Level in Mice Subjected to Hemorrhagic Shock/Resuscitation.
Zhang, Li; Tian, Feng; Gao, Xuejin; Wang, Xinying; Wu, Chao; Li, Ning; Li, Jieshou
Appropriate metabolic interventions after hemorrhagic shock/resuscitation injury have not yet been identified. We aimed to examine the effects of fish oil on lipid metabolic intervention after hemorrhagic shock/resuscitation. Firstly, 48 C57BL/6 mice were assigned to six groups (n = 8 per group). The sham group did not undergo surgery, while mice in the remaining groups were sacrificed 1-5 days after hemorrhagic shock/resuscitation. In the second part, mice were treated with saline or fish oil (n = 8 per group) five days after injury. We determined serum triglyceride levels and liver tissues were collected and prepared for qRT-PCR or Western blot analysis. We found that triglyceride levels were increased five days after hemorrhagic shock/resuscitation, but decreased after addition of fish oil. After injury, the protein and gene expression of carnitine palmitoyltransferase 1A, fatty acid transport protein 1, and peroxisome proliferator-activated receptor-α decreased significantly in liver tissue. In contrast, after treatment with fish oil, the expression levels of these targets increased compared with those in the saline group. The present results suggest n-3 polyunsaturated fatty acids could improve lipid oxidation-related enzymes in liver subjected to hemorrhagic shock/resuscitation. This function is possibly accomplished through activating the peroxisome proliferator-activated receptor-α pathway.
The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 PUFA is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and dependent on cholesterol status. To further elucidate the mechanism(...
Omega-3 fatty acids are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount of triglycerides (a fat-like ... people with very high triglycerides. Omega-3 fatty acids are in a class of medications called antilipemic ...
De Boer, Anna A; Monk, Jennifer M; Liddle, Danyelle M; Power, Krista A; Ma, David W L; Robinson, Lindsay E
Adipose tissue (AT) macrophages (ATM) play a key role in obesity-associated pathologies, and their phenotype can be influenced by the local tissue microenvironment. Interestingly, long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) and the LC n-3 PUFA-upregulated adipokine, adiponectin (Ad), may mitigate excessive ATM inflammatory M1-polarization responses. However, to what extent LC n-3 PUFA and Ad work in concert to affect macrophage phenotype has not been examined. Thus, we used an established ex vivo AT organ culture model using visceral AT from mice fed a control (CON; 10% w/w safflower oil) n-6 PUFA-rich diet or an isocaloric fish oil (FO; 3% w/w menhaden oil + 7% w/w safflower oil)-derived LC n-3 PUFA-rich diet to generate AT conditioned media (ACM). We then evaluated if CON or FO ACM affected macrophage polarization markers in a model designed to mimic acute [18 h ACM plus lipopolysaccharide (LPS) for the last 6 h] or chronic (macrophages treated with LPS-challenged CON or FO ACM for 24 h) inflammation ± Ad-neutralizing antibody and the LPS-neutralizing agent, polymyxin B. In the acute inflammation model, macrophages treated with FO ACM had decreased lipid uptake and mRNA expression of M1 markers (Nos2, Nfκb, Il6, Il18, Ccl2, and Ccl5) compared with CON ACM (p ≤ 0.05); however, these effects were largely attenuated when Ad was neutralized (p > 0.05). Furthermore, in the chronic inflammation model, macrophages treated with FO ACM had decreased mRNA expression of M1 markers (Nos2, Tnfα, Ccl2, and Il1β) and IL-6 and CCL2 secretion (p ≤ 0.05); however, some of these effects were lost when Ad was neutralized, and were further exacerbated when both Ad and LPS were neutralized. Taken together, this work shows that LC n-3 PUFA and Ad work in concert to suppress certain M1 macrophage responses. Thus, future strategies to modulate the ATM phenotype should consider the role of both LC n-3 PUFA and Ad in mitigating obese AT
Effect of maternal n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and/or lactation on adiposity in childhood: a systematic review and meta-analysis of randomized controlled trials.
Stratakis, N; Gielen, M; Chatzi, L; Zeegers, M P
It is hypothesized that prenatal and early postnatal exposure to n-3 long-chain polyunsaturated fatty acids (LCPUFAs) is negatively associated with adiposity later in life. We conducted a systematic review and meta-analysis to evaluate whether maternal n-3 LCPUFA supplementation in pregnancy and/or lactation exerts a beneficial effect on adiposity status in childhood. We searched six electronic databases till 20 May 2014 for randomized controlled trials (RCTs) of n-3 LCPUFA supplementation to pregnant and/or lactating women that reported data on body mass index (BMI), waist circumference, sum of skinfold thicknesses or body fat mass in children. Adiposity measures were grouped into three age categories: preschool children (<5 years), school-aged children (6-12 years), and adolescents (>13 years). Trial quality was assessed. We conducted fixed-effect and random-effects meta-analyses to combine study-specific estimates of differences between the supplemented and control groups. A total of 6 RCTs (9 publications) involving 2847 participants were included. Summary estimates showed no effect of maternal supplementation on BMI in preschool (standardized mean difference (SMD)=0.07, 95% confidence interval (CI)=-0.22, 0.36, P=0.65) and school-aged children (SMD=0.12, 95% CI=-0.06, 0.30, P=0.20). Because of sparse data, it was not possible to pool study results relating to other adiposity measures. There is currently no evidence to support that n-3 LCPUFA supplementation during pregnancy and/or lactation favourably affects child adiposity. Further high-quality trials are needed.
Reis, Caio Eduardo Gonçalves; Landim, Karla Câmara; Nunes, Aline Costa Santos; Dullius, Jane
Introducción: Diabetes mellitus tipo 2 aumenta el riesgo de hipertrigliceridemia y es un factor de riesgo independiente para las enfermedades cardiovasculares. La literatura actual revela efectos beneficiosos de n-3 ácidos grasos poliinsaturados (n-3 AGPI) en el tratamiento de la hipertrigliceridemia, sin embargo, la seguridad de este tratamento en los sujetos diabéticos tipo 2 es discutible. Esta revisión de la literatura discute la seguridad del n-3 PUFA la suplementación sobre el metabolismo de la glucosa en el tratamiento de la hipertrigliceridemia en pacientes con diabetes mellitus tipo 2. Métodos: Se ha realizado una revisión de la literatura en la base de datos MEDLINE y EMBASE del los ensayos clínicos publicados con fecha posterior al 1990 hasta Junio de 2014 sobre los efectos de la ingesta / suplementos del n-3 AGPI en el tratamiento de la hipertrigliceridemia en pacientes con diabetes mellitus tipo 2. Resultados y Discusión: Catorce estudios clínicos (n = 2105) se incluyeron en esta revisión. Del estudios informaron una reducción en los niveles de triglicéridos entre 12 a 34% en interior del grupo comparación y de 15 a 36% en entre grupos análisis. Cuatro estudios mostraron un aumento significativo en el LDL-c (6-18%) y otros cuatro en los niveles de HDL-c (4 - 15%). No se encontraron cambios significativos en el colesterol total, VLDL-c, la glucosa, HbA1c y el índice de sensibilidad a la insulina. Conclusión: El n-3 AGPI suplementación lleva una mejora en los niveles de triglicéridos y no arrojaron deterioro en el metabolismo de la glucosa en pacientes con hipertrigliceridemia con diabetes mellitus tipo 2 siendo una opción segura para el tratamiento de la población diabética.
Sinn, Natalie; Milte, Catherine M; Street, Steven J; Buckley, Jonathan D; Coates, Alison M; Petkov, John; Howe, Peter R C
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.
Shanklin, John; Cahoon, Edgar B.
The present invention relates to a method for producing mutants of a fatty acid desaturase having a substantially increased activity towards fatty acid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fatty acid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fatty acids, thereby selecting for recipient cells which have received and which express a mutant fatty acid desaturase with an elevated specificity for fatty acid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fatty acid products.
Fats and their various fatty acid components seem to be a perennial concern of nutritionists and persons concerned with healthful diets. Advice on the consumption of saturated, polyunsaturated, monounsaturated, and total fat bombards us from magazines and newspapers. One of the newer players in this field is the group of trans fatty acids found predominantly in partially hydrogenated fats such as margarines and cooking fats. The controversy concerning dietary trans fatty acids was recently addressed in an American Heart Association (AHA) science advisory (1) and in a position paper from the American Society of Clinical Nutrition/American Institute of Nutrition (ASCN/AIN) (2). Both reports emphasize that the best preventive strategy for reducing risk for cardiovascular disease and some types of cancer is a reduction in total and saturated fats in the diet, but a reduction in the intake of trans fatty acids was also recommended. Although the actual health effects of trans fatty acids remain uncertain, experimental evidence indicates that consumption of trans fatty acids adversely affects serum lipid levels. Since elevated levels of serum cholesterol and triacylglycerols are associated with increased risk of cardiovascular disease, it follows that intake of trans fatty acids should be minimized.
Vissapragada, Sarada; Ghosh, Anup; Ringer, Lymor; Salinas, Patricia; Brophy, Amanda; Peaceman, Daniel; Kallakury, Bhaskar; Banerjee, Partha P; Fricke, Stanley T; Helfrich, William; Lee, Yi Chien; Pestell, Richard; Scherer, Philipp; Tanowitz, Herbert B; Avantaggiati, Maria Laura; Hilakivi-Clarke, Leena; Lisanti, Michael P; Rodriguez, Olga C; Albanese, Chris
Diet and obesity, and their associated metabolic alterations, are some of the fastest-growing causes of disease and death in America. Findings from epidemiological studies correlating obesity, the sources of dietary fat and prostate cancer (PCa) are conflicting. We have previously shown that 15% of PB-ErbB-2 x pten(+/-) mice developed PCa and exhibited increased phosphorylated 4E-BP1, but not the key PI3-kinase intermediary phospho-protein, mTOR, when maintained on unrefined mouse chow. We report herein that 100% of animals fed refined, westernized AIN-93-based diets containing corn oil developed PCa by 12 months of age. Increases in visceral fat and mTO R activation in the tumors were also observed. Furthermore, nuclear cyclin E levels were significantly induced by the AIN-93-corn oil-based diets versus chow. Replacing 50% of the corn oil with menhaden oil, with 21% of its triglycerides being n-3 PUFA's, had no effect on tumorigenesis, fat deposition, cyclin E or mTOR. Phosphorylated BAD levels were similar in the tumors of mice in all three diets. Our data demonstrated that in the context of our preclinical model, components of crude chow, but not dietary n-3 PUFAs, protect against PCa progression. In addition, these data establish phosphorylated mTOR, nuclear cyclin E and visceral fat deposits as possible biomarkers of increased dietary risk for PCa.
Laird, Brian D; Goncharov, Alexey B; Egeland, Grace M; Chan, Hing Man
Elevated concentrations of mercury (Hg) are commonly found in the traditional foods, including fish and marine mammals, of Inuit living in Canada's Arctic. As a result, Inuit often have higher dietary Hg intake and elevated Hg blood concentrations. However, these same traditional foods are excellent sources of essential nutrients. The goals of this study were 1) to identify the traditional food sources of Hg exposure for Inuit, 2) to estimate the percentage of Inuit who meet specific nutrient Dietary Reference Intakes and/or exceed the Toxicological Reference Values (TRVs), and 3) to evaluate options that maximize nutrient intake while minimizing contaminant exposure. A participatory cross-sectional survey was designed in consultation with Inuit in 3 Canadian Arctic jurisdictions (Nunatsiavut, Nunavut, and the Inuvialuit Settlement Region). Estimated intakes for EPA (20:5n3) and DHA (22:6n3) met suggested dietary targets, and estimated selenium (Se) intake fell within the Acceptable Range of Oral Intake. Estimated intakes of Hg (rs = 0.41, P < 0.001), Se (rs = 0.44, P < 0.001), EPA (rs = 0.32, P < 0.001), and DHA (rs = 0.28, P < 0.001) were correlated with their respective blood concentrations. Mean estimated Hg intake (7.9 μg · kg(-1) · wk(-1)) exceeded the TRV of 5.0 μg · kg(-1) · wk(-1), with 35% of the population above this guideline. Because the estimated intakes of each of the nutrients were strongly correlated (Se: rs = 0.92, P < 0.001; EPA: rs = 0.82, P < 0.001; DHA: rs = 0.81, P < 0.001) with estimated Hg intake, efforts to decrease Hg exposure must emphasize the overall healthfulness of traditional foods and be designed to prevent concomitant harm to the nutrient intakes of Inuit.
Huang, Tao; Li, Kelei; Asimi, Sailimuhan; Chen, Qi; Li, Duo
目的：维生素B-12 和欧米伽3 多不饱和脂肪酸能够降低血液同型半胱氨酸浓 度。但是，这两种营养元素是否对同型半胱氨酸、铁蛋白、C 反应蛋白有协 同效应仍不清楚。方法：为进一步解决该问题，我们开展了一项随机对照实 验，38 位参与者随机分为三组，每天分别食用1000 μg 维生素B-12、2 g 鱼 油、1000 μg 维生素B-12+2 g 鱼油。八周以后，收集受试者血样，测定血浆磷 脂脂肪酸组成，生物标志物等。结果：四周或者八周干预以后，鱼油组和鱼 油+维生素B-12 组的血浆磷脂20:5n-3、22:6n-3 和总欧米伽3 脂肪酸显著升 高，然而，血浆甘油三酯、尿酸、C 反应蛋白以及铁蛋白显著降低。维生素 B-12 组、鱼油组、维生素B-12+鱼油组，血浆同型半胱氨酸分别降低22%、19% 和39%。结论：维生素B-12 和鱼油在调节同型半胱氨酸代谢过程中存在协同 效应。.
Young, Genevieve; Conquer, Julie
Epidemiological evidence suggests that dietary consumption of the long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), commonly found in fish or fish oil, may modify the risk for certain neuropsychiatric disorders. As evidence, decreased blood levels of omega-3 fatty acids have been associated with several neuropsychiatric conditions, including Attention Deficit (Hyperactivity) Disorder, Alzheimer's Disease, Schizophrenia and Depression. Supplementation studies, using individual or combination omega-3 fatty acids, suggest the possibility for decreased symptoms associated with some of these conditions. Thus far, however, the benefits of supplementation, in terms of decreasing disease risk and/or aiding in symptom management, are not clear and more research is needed. The reasons for blood fatty acid alterations in these disorders are not known, nor are the potential mechanisms by which omega-3 fatty acids may function in normal neuronal activity and neuropsychiatric disease prevention and/or treatment. It is clear, however, that DHA is the predominant n-3 fatty acid found in the brain and that EPA plays an important role as an anti-inflammatory precursor. Both DHA and EPA can be linked with many aspects of neural function, including neurotransmission, membrane fluidity, ion channel and enzyme regulation and gene expression. This review summarizes the knowledge in terms of dietary omega-3 fatty acid intake and metabolism, as well as evidence pointing to potential mechanisms of omega-3 fatty acids in normal brain functioning, development of neuropsychiatric disorders and efficacy of omega-3 fatty acid supplementation in terms of symptom management.
We previously reported that feeding mice high-fat (HF) diets enriched with eicosapentaenoic acid (EPA) decreased inflammation, adiposity and insulin resistance. In the current study, we used skeletal muscle from mice fed HF or HF-EPA for 11 weeks to further dissect mechanisms mediating EPA effects o...
Long-chain polyunsaturated fatty acids (LCPUFA, or LCP) include the essential fatty acids alpha-linolenic acid (ALA, 18:3 n-3) and linoleic acid (LA, 18:2 n-6) as well as a number of metabolites of both, including eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachid...
Broadhurst, C. Leigh; Schmidt, Walter F.; Kim, Moon S.; Nguyen, Julie K.; Qin, Jianwei; Chao, Kuanglin; Bauchan, Gary L.; Shelton, Daniel R.
The structural, cognitive and visual development of the human brain and retina strictly require long-chain polyunsaturated fatty acids (LC-PUFA). Excluding water, the mammalian brain is about 60% lipid. One of the great unanswered questions with respect to biological science in general is the absolute necessity of the LC-PUFA docosahexaenoic acid (DHA; 22:6n-3) in these fast signal processing tissues. A lipid of the same chain length with just one less diene group, docosapentaenoic acid (DPA; 22:5n-6) is fairly abundant in terrestrial food chains yet cannot substitute for DHA. Gradient Temperature Raman spectroscopy (GTRS) applies the temperature gradients utilized in differential scanning calorimetry to Raman spectroscopy, providing a straightforward technique to identify molecular rearrangements that occur near and at phase transitions. Herein we apply GTRS to DPA, and DHA from -100 to 20°C. 20 Mb three-dimensional data arrays with 1°C increments and first/second derivatives allows complete assignment of solid, liquid and transition state vibrational modes, including low intensity/frequency vibrations that cannot be readily analyzed with conventional Raman. DPA and DHA show significant spectral changes with premelting (-33 and -60°C, respectively) and melting (-27 and -44°C, respectively). The CH2-(HC=CH)-CH2 moieties are not identical in the second half of the DHA and DPA structures. The DHA molecule contains major CH2 twisting (1265 cm-1) with no noticeable CH2 bending, consistent with a flat helical structure with small pitch. Further modeling of neuronal membrane phospholipids must take into account this structure for DHA, which would be configured parallel to the hydrophilic head group line.
Essential fatty acids (EFA) are nutrients that form an amazingly large array of bioactive mediators that act on a large family of selective receptors. Nearly every cell and tissue in the human body expresses at least one of these receptors, allowing EFA-based signaling to influence nearly every aspect of human physiology. In this way, the health consequences of specific gene-environment interactions with these nutrients are more extensive than often recognized. The metabolic transformations have similar competitive dynamics for the n-3 and n-6 homologs when converting dietary EFA from the external environment of foods into the highly unsaturated fatty acid (HUFA) esters that accumulate in the internal environment of cells and tissues. In contrast, the formation and action of bioactive mediators during tissue responses to stimuli tend to selectively create more intense consequences for n-6 than n-3 homologs. Both n-3 and n-6 nutrients have beneficial actions, but many common health disorders are undesired consequences of excessive actions of tissue n-6 HUFA which are preventable. This review considers the possibility of preventing imbalances in dietary n-3 and n-6 nutrients with informed voluntary food choices. That action may prevent the unintended consequences that come from eating imbalanced diets which support excessive chronic actions of n-6 mediators that harm human health. The consequences from preventing n-3 and n-6 nutrient imbalances on a nationwide scale may be very large, and they need careful evaluation and implementation to avoid further harmful consequences for the national economy. PMID:23112921
Spector, Arthur A.; Kim, Hee-Yong
Dietary fat was recognized as a good source of energy and fat-soluble vitamins by the first part of the 20th century, but fatty acids were not considered to be essential nutrients because they could be synthesized from dietary carbohydrate. This well-established view was challenged in 1929 by George and Mildred Burr who reported that dietary fatty acid was required to prevent a deficiency disease that occurred in rats fed a fat-free diet. They concluded that fatty acids were essential nutrients and showed that linoleic acid prevented the disease and is an essential fatty acid. The Burrs surmised that other unsaturated fatty acids were essential and subsequently demonstrated that linolenic acid, the omega-3 fatty acid analog of linoleic acid, is also an essential fatty acid. The discovery of essential fatty acids was a paradigm-changing finding, and it is now considered to be one of the landmark discoveries in lipid research. PMID:25339684
Al-Arrayedu, F. H.; Al Maskati, H. A.; Abdullah, F. J.
This study was performed to determine the content of n3- polyunsaturated fatty acids in 10 fish species that are commonly consumed in Bahrain in addition to the main commercial shrimp species. White sardinella, which is a plankton feeder, had the highest content of n3- polyunsaturated fatty acids. It had the highest value of eicosapentaenoic acid (146.5 ± 20 mg 100 g-1) and linolenic acid (98.9±f 100 g-1) and the second highest value of docosahexaenoic acid at (133.7 ± 22 mg 100 g-1). Spanish mackerel which feeds mainly on sardinella was second with eicosapentaenoc acid at 55 ± 5.4 mg 100 g-1, docosahexaenoic acid at 161 ± 19.8 mg 100 g-1, linolenic acid at 16.4 mg 100 g-1 and docosapentaenoic acid at 25 ± 1.9 mg 100 g-1. Rabbitfish, the most popular edible fish in Bahrain which feeds mainly on benthic algae had the third highest content of n3- polyunsaturated fatty acids with eicosapentaenoic acid at 37.5 ± 3.9 mg 100 g-1, docosahexaenoic acid at 76 ± 6.7 mg 100 g-1, and docosapentaenoic acid at 85.8 ± 10 mg 100 g-1. The other fish and crustacean species studied were Arabian carpet shark, doublebar bream, grouper, gray grunt, golden travally, keeled mullet, spangled emperor and shrimp. The study explores the transfer of n3- polyunsaturated fatty acids through the food webs of the examined fish. It is apparent, generally, that plankton feeders displayed the highest content of n3- polyunsaturated fatty acids followed by seaweed and algae grazers, with benthic carnivores feeding on invertebrates displaying the poorest content. The values reported here, however, are much lower than those reported for fish available in American markets and in Mediterranean fish. Warm water temperature and high salinity which lead to lowering of the density of phytoplankton and phytoplankton content of n3- polyunsaturated fatty acids are suggested as the reason for the observed low values of n3- polyunsaturated fatty acids in Bahrain fish.
Omega-3 fatty acids are a form of polyunsaturated fat that the body derives from food. Omega-3s (and omega-6s) are known as essential fatty acids (EFAs) because they are important for good health. ...
Schuchardt, Jan Philipp; Hahn, Andreas
Supplements have reached a prominent role in improving the supply of long-chain omega-3 fatty acids, such as Eicosapentaenoic acid (EPA 20:5n-3) and Docosahexaenoic acid (DHA 22:6n-3). Similar to other nutrients, the availability of omega-3 fatty acids is highly variable and determined by numerous factors. However, the question of omega-3 fatty acids bioavailability has long been disregarded, which may have contributed to the neutral or negative results concerning their effects in several studies. This review provides an overview of the influence of chemical binding form (free fatty acids bound in ethylesters, triacylglycerides or phospholipids), matrix effects (capsule ingestion with concomitant intake of food, fat content in food) or galenic form (i.e. microencapsulation, emulsification) on the bioavailability of omega-3 fatty acids. There is a need to systematically investigate the bioavailability of omega-3 fatty acids formulations, which might be a key to designing more effective studies in the future.
The structural, cognitive and visual development of the human brain and retina strictly require long-chain polyunsaturated fatty acids (LC-PUFA). Excluding water, the mammalian brain is about 60% lipid. One of the great unanswered questions with respect to biological science in general is the absolu...
Njoroge, Sarah W; Laposata, Michael; Boyd, Kelli L; Seegmiller, Adam C
Cystic fibrosis patients and model systems exhibit consistent abnormalities in metabolism of polyunsaturated fatty acids that appear to play a role in disease pathophysiology. Recent in vitro studies have suggested that these changes are due to overexpression of fatty acid desaturases that can be reversed by supplementation with the long-chain polyunsaturated fatty acids docosahexaenoate and eicosapentaenoate. However, these findings have not been tested in vivo. The current study aimed to test these results in an in vivo model system, the CFTR(-/-) knockout mouse. When compared with wild-type mice, the knockout mice exhibited fatty acid abnormalities similar to those seen in cystic fibrosis patients and other model systems. The abnormalities were confined to lung, ileum and pancreas, tissues that are affected by the disease. Similar to in vitro models, these fatty acid changes correlated with increased expression of Δ5- and Δ6-desaturases and elongase 5. Dietary supplementation with high-dose free docosahexaenoate or a combination of lower-dose docosahexaenoate and eicosapentaenoate in triglyceride form corrected the fatty acid abnormalities and reduced expression of the desaturase and elongase genes in the ileum and liver of knockout mice. Only the high-dose docosahexaenoate reduced histologic evidence of disease, reducing mucus accumulation in ileal sections. These results provide in vivo support for the hypothesis that fatty acid abnormalities in cystic fibrosis result from abnormal expression and activity of metabolic enzymes in affected cell types. They further demonstrate that these changes can be reversed by dietary n-3 fatty acid supplementation, highlighting the potential therapeutic benefit for cystic fibrosis patients.
Pfleger, Brian F; Lennen, Rebecca M
Described are hosts for overproducing a fatty acid product such as a fatty acid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at 37.degree. C. Methods of producing a fatty acid product comprising culturing such hosts at 37.degree. C. are also described.
association betw een omega -3 fatty acids (n-3 PUFA ) and low er risk of breast cancer. Although experimental animal studies indicate that including n-3...1-0375 TITLE: Induction of a Pregnancy-Like Mammary Gland Differentiation by Docosapentaenoic Omega -3 Fatty Acid PRINCIPAL INVESTIGATOR...during pregnancy. Considerable evidences suggest strongly that the n-3 polyunsaturated fatty acid ( PUFA ) content of adipose breast tissue is
... of fatty acid oxidation disorders Treatment of fatty acid oxidation disorders E-mail to a friend Please ... page It's been added to your dashboard . Fatty acid oxidation disorders are rare health conditions that affect ...
Simopoulos, A P
Human beings evolved consuming a diet that contained about equal amounts of n-3 and n-6 essential fatty acids. Over the past 100-150 y there has been an enormous increase in the consumption of n-6 fatty acids due to the increased intake of vegetable oils from corn, sunflower seeds, safflower seeds, cottonseed, and soybeans. Today, in Western diets, the ratio of n-6 to n-3 fatty acids ranges from approximately 20-30:1 instead of the traditional range of 1-2:1. Studies indicate that a high intake of n-6 fatty acids shifts the physiologic state to one that is prothrombotic and proaggregatory, characterized by increases in blood viscosity, vasospasm, and vasoconstriction and decreases in bleeding time. n-3 Fatty acids, however, have antiinflammatory, antithrombotic, antiarrhythmic, hypolipidemic, and vasodilatory properties. These beneficial effects of n-3 fatty acids have been shown in the secondary prevention of coronary heart disease, hypertension, type 2 diabetes, and, in some patients with renal disease, rheumatoid arthritis, ulcerative colitis, Crohn disease, and chronic obstructive pulmonary disease. Most of the studies were carried out with fish oils [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. However, alpha-linolenic acid, found in green leafy vegetables, flaxseed, rapeseed, and walnuts, desaturates and elongates in the human body to EPA and DHA and by itself may have beneficial effects in health and in the control of chronic diseases.
Howie, A; Leaver, H A; Wilson, N H; Yap, P L; Aitken, I D
The effect of dietary fatty acids on uterine fatty acid composition was studied in rats fed control diet or semi-synthetic diet supplemented with 1.5 microliter/g/day evening primrose oil (EPO) or fish oil (FO). Diet-related changes in uterine lipid were detected within 21 days. Changes of 2- to 20-fold were detected in the uterine n-6 and n-3 essential fatty acids (EFA) and in certain saturated and monounsaturated fatty acids. The FO diet was associated with higher uterine C20 and C22 n-3, and the EPO diet, with higher uterine n-6 fatty acid. High uterine C18:2 n-6 was detected in neutral lipid (NL) of rats fed high concentrations of this fatty acid, but there was little evidence of selective incorporation or retention of C18:2 n-6 by uterine NL. The incorporation of EFA into uterine phospholipids (PL) was greater than NL EFA incorporation, and uterine PL n-3/n-6 ratios showed greater diet dependence. Tissue/diet fatty acid ratios in NL and PL also indicated preferential incorporation/synthesis of C16:1 n-9, and C16:0, and there was greater incorporation of C12:0 and C14:0 into uteri of rats fed EPO and FO. Replacement of 50-60% of arachidonate with n-3 EFA in uterine PL may inhibit n-6 EFA metabolism necessary for uterine function at parturition.
Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung
Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism. PMID:26742061
Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung
Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism.
Inflammation is overall a protective response, whose main goal is to liberate the human being of cellular lesions caused by micro-organisms, toxins, allergens, etc., as well as its consequences, and of death cells and necrotic tissues. Chronic inflammation, which is detrimental to tissues, is the basic pathogenic mechanism of hypersensitivity reactions against xenobiotics. Other frequent pathologies, for instance atherosclerosis, chronic hepatitis, inflammatory bowel disease (IBD), liver cirrhosis, lung fibrosis, psoriasis, and rheumatoid arthritis are also chronic inflammatory diseases. Chemical mediators of inflammation are derived from blood plasma or different cell-type activity. Biogenic amines, eicosanoids and cytokines are within the most important mediators of inflammatory processes. The different activities of eicosanoids derived from arachidonic acid (20:4 n-6) versus those derived from eicosapentaenoic acid (20:5 n-3) are one of the most important mechanisms to explain why n-3, or omega-3, polyunsaturated fatty acids (PUFA) exhibit anti-inflammatory properties in many inflammatory diseases. Dietary supplements ranging 1-8 g per day of n-3 PUFA have been reportedly beneficial in the treatment of IBD, eczema, psoriasis and rheumatoid arthritis. In addition, recent experimental studies in rats with experimental ulcerative colitis, induced by intrarectal injection of trinitrobenzene sulphonic acid, have documented that treatment with n-3 long-chain PUFA reduces mucosal damage as assessed by biochemical and histological markers of inflammation. Moreover, the defence antioxidant system in this model is enhanced in treated animals, provided that the n-3 PUFA supply is adequately preserved from oxidation.
Kang, Jing X; Gleason, Erin D
The mammalian brain and central nervous system are especially dependent on the omega-3 (n-3) fatty acid docosahexaenoic acid (DHA) for normative signaling and function, and research suggests that n-3 fatty acid deficiencies are one contributing factor in the increasing prevalence of depressive disorders. However, the reasons for which n-3 fatty acids and mood are connected remain unknown. Atrophy in the hippocampus is one of the most significant neuroanatomical findings in depressed patients, and current therapies for depression tend to increase hippocampal neurogenesis. We recently discovered that the fat-1 transgenic mouse, which has enriched levels of DHA in the brain because it can convert n-6 to n-3 fatty acids, exhibits increased hippocampal neurogenesis. This finding suggests a mechanism by which omega-3 could influence depression and mood; here we expand on the argument that n-3 fatty acids, and DHA in particular, may help prevent and treat depression by virtue of their effects on neurogenesis in the hippocampus. Because DHA can be obtained through the diet, increasing DHA intake in depressed patients or those at risk for depression may be one way of managing the disease and perhaps providing aid to those who have not been able to achieve remission via pharmacological means.
Leach, W. W.; Nooner, D. W.; Oro, J.
The formation of fatty acids by Fischer-Tropsch-type synthesis was investigated with ferric oxide, ammonium carbonate, potassium carbonate, powdered Pueblito de Allende carbonaceous chondrite, and filings from the Canyon Diablo meteorite used as catalysts. Products were separated and identified by gas chromatography and mass spectrometry. Iron oxide, Pueblito de Allende chondrite, and Canyon Diablo filings in an oxidized catalyst form yielded no fatty acids. Canyon Diablo filings heated overnight at 500 C while undergoing slow purging by deuterium produced fatty acids only when potassium carbonate was admixed; potassium carbonate alone also produced these compounds. The active catalytic combinations gave relatively high yields of aliphatic and aromatic hydrocarbons; substantial amounts of n-alkenes were almost invariably observed when fatty acids were produced; the latter were in the range C6 to C18, with maximum yield in C9 or 10.
Torres, Alexandre G; Ney, Jacqueline G; Meneses, Flávia; Trugo, Nádia M F
Maternal adipose tissue is a major contributor to breast milk long-chain fatty acids, probably through the pool of plasma NEFA. The fatty acid composition of the erythrocyte membrane (EM) is a biochemical index of the intake of fatty acids not synthesized endogenously and of PUFA and long-chain PUFA fatty acid status. The present study investigated the associations between breast milk fatty acid composition and the composition of plasma NEFA and of EM fatty acids with special reference to PUFA, long-chain PUFA and conjugated linoleic acid (CLA). The detailed fatty acid composition of mature breast milk was also reported. Thirty-three healthy, lactating Brazilian women donated milk samples; of these, twenty-four also donated blood samples in an observational cross-sectional study. Breast milk fatty acid composition presented several associations with NEFA and EM composition, which explained most (> or =50 %) of the variability of selected milk PUFA, long-chain PUFA and CLA. Milk CLA was associated with fatty acids that are markers of dairy fat intake in the diet, NEFA and EM. In general, breast milk n-3 fatty acids and CLA, but not n-6 fatty acids, were associated with EM composition, whereas both the n-6 and n-3 fatty acids and CLA in milk were associated with NEFA composition, possibly owing to its role as a direct source of fatty acids for breast milk. These findings emphasize the contribution of the NEFA pool derived from the adipose tissue to the long-chain fatty acid composition of breast milk.
Mossaheb, Nilufar; Schloegelhofer, Monika; Schaefer, Miriam R; Fusar-Poli, Paolo; Smesny, Stefan; McGorry, Pat; Berger, Gregor; Amminger, G Paul
The role of polyunsaturated fatty acids and their metabolites for the cause and treatment of psychotic disorders are widely discussed. The efficacy as an augmenting agent in chronic schizophrenia seems to be small or not present, however epidemiological data, as well as some recent controlled studies in emerging psychosis point towards possible preventive effects of long-chain polyunsaturated fatty acids in early and very early stages of psychotic disorders and some potential secondary or tertiary beneficial long-term effects in later, more chronic stages, in particular for metabolic or extra-pyramidal side effects. In this comprehensive review, we describe the physiology and metabolism of polyunsaturated fatty acids, phospholipases, epidemiological evidence and the effect of these fatty acids on the brain and neurodevelopment. Furthermore, we examine the available evidence in indicated prevention in emerging psychosis, monotherapy, add-on therapy and tolerability. The neuroprotective potential of n-3 LC-PUFAs for indicated prevention, i.e. delaying transition to psychosis in high-risk populations needs to be further explored.
Rode, A; Shephard, R J; Vloshinsky, P E; Kuksis, A
Cross-sectional data from 86 male and 59 female coastal Inuit of Igloolik (69 degrees 40'N, 81 degrees W) showed a steep age-related increase in the percentage of plasma n-3 fatty acids, with parallel trends in 20:5 and 22:6 but not 18:3 n-3 fatty acid concentrations. Omega-7 + 9 (p < .001) and omega-9 fatty acid concentrations (P < .001 in M, .008 in F) also decreased with age. A tundra-based Siberian indigenous population (30 male and 11 female nGanasan) had similar percentages of n-3 and n-6 fatty acids to the young Inuit, with little age-related change in either measure. Correlation matrices for the Inuit men showed quite strong negative associations of n-3 fatty acid percentages with total triglycerides (r = .34, p < .001) and phosphatidylcholine/free cholesterol ratio (r = -.36, p < .001). In the Inuit women, n-3 percentages were strongly related to phosphatidylcholine/free cholesterol ratio (r = -.60, p < .001), but not to triglyceride readings. The phosphatidylcholine/free cholesterol ratio was also correlated with n-6 percentages (r = -.55, p < .001). In the nGanasan men, triglyceride levels were correlated with n-6 (r = -.35, p < .050), but the size of the female sample was insufficient to establish useful correlations. The present data suggest that as the younger coastal Inuit are abandoning their traditional country foods, plasma levels of n-3 fall. Reasons why n-3 fatty acid levels are negatively related to the plasma phosphatidyl choline/free cholesterol ratio merit further investigation.
Shen, Pei-Li; Wang, Hai-Tao; Pan, Yan-Fei; Meng, Ying-Ying; Wu, Pei-Chun; Xue, Song
The fatty acid profiles of lipids from microalgae are unique. Polyunsaturated fatty acids are generally enriched in polar lipids, whereas saturated and monounsaturated fatty acids constitute the majority of fatty acids in triacylglycerols (TAG). Each species has characteristic fatty acids, and their content is positively or negatively correlated with TAGs. The marine oleaginous diatom Phaeodactylum tricornutum was used as the paradigm to determine the quantitative relationship between TAG and characteristic fatty acid content. Fatty acid profiles and TAG content of Phaeodactylum tricornutum were determined in a time course. C16:0/C16:1 and eicosapentaenoic acid (EPA, C20:5n3) were identified as characteristic fatty acids in TAGs and polar lipids, respectively. The percentage of those characteristic fatty acids in total fatty acids had a significant linear relationship with TAG content, and thus, the correlation coefficient presenting r2 were 0.96, 0.94, and 0.97, respectively. The fatty acid-based method for TAG quantification could also be applied to other microalgae such as Nannochloropsis oceanica in which the r2 of C16:0 and EPA were 0.94 and 0.97, respectively, and in Chlorella pyrenoidosa r2-values for C18:1 and C18:3 with TAG content were 0.91 and 0.99, repectively. This characteristic fatty acid-based method provided a distinct way to quantify TAGs in microalgae, by which TAGs could be measured precisely by immediate transesterification from wet biomass rather than using conventional methods. This procedure simplified the operation and required smaller samples than conventional methods. PMID:26941747
Lipid peroxidation of polyunsaturated fatty acids yields several electrophilic, reactive carbonyl metabolites. We hypothesized that an increased intake of omega-3 fatty acids (n-3) would lead to increased lipid peroxidation metabolites compared to a diet low in n-3. As part of a randomized crossov...
Lochmann, R T; Gatlin, D M
Feeding experiments and laboratory analyses were conducted to establish the essential fatty acid (EFA) requirement of red drum (Sciaenops ocellatus). Juvenile red drum were maintained in aquaria containing brackish water (5 ± 2‰ total dissolved solids) for two 6-week experiments. Semipurified diets contained a total of 70% lipid consisting of different combinations of tristearin [predominantly 18:0] and the following fatty acid ethyl esters: oleate, linoleate, linolenate, and a mixture of highly unsaturated fatty acids (HUFA) containing approximately 60% eicosapentaenoate plus docosahexaenoate. EFA-deficient diets (containing only tristearin or oleate) rapidly reduced fish growth and feed efficiency, and increased mortality. Fin erosion and a "shock syndrome" also occurred in association with EFA deficiency. Of the diets containing fatty acid ethyl esters, those with 0.5-1% (n-3) HUFA (0.3-0.6% eicosapentaenoate plus docosahexaenoate) promoted the best growth, survival, and feed efficiency; however, the control diet containing 7% menhaden fish oil provided the best performance. Excess (n-3) HUFA suppressed fish weight gain; suppression became evident at 1.5% (n-3) HUFA, and was pronounced at 2.5%. Fatty acid compositions of whole-body, muscle and liver tissues from red drum fed the various diets generally reflected dietary fatty acids, but modifications of these patterns also were evident. Levels of saturated fatty acids appeared to be regulated independent of diet. In fish fed EFA-deficient diets (containing only tristearin or oleate), monoenes increased and (n-3) HUFA were preferentially conserved in polar lipid fractions. Eicosatrienoic acid [20:3(n-9)] was not elevated in EFA-deficient red drum, apparently due to their limited ability to transform fatty acids. Red drum exhibited some limited ability to elongate and desaturate linoleic acid [18:2(n-6)] and linolenic acid [18:3(n-3)]; however, metabolism of 18:3(n-3) did not generally result in increased
Rodrigues, Hosana G; Takeo Sato, Fabio; Curi, Rui; Vinolo, Marco A R
Neutrophils are well-known to act in the destruction of invading microorganisms. They have also been implicated in the activation of other immune cells including B- and T-lymphocytes and in the resolution of inflammation and tissue regeneration. Neutrophils are produced in the bone marrow and released into the circulation from where they migrate to tissues to perform their effector functions. Neutrophils are in constant contact with fatty acids that can modulate their function, activation and fate (survival or cell death) through different mechanisms. In this review, the effects of fatty acids pertaining to five classes, namely, long-chain saturated fatty acids (LCSFAs), short-chain fatty acids (SCFAs), and omega-3 (n-3), omega-6 (n-6) and omega-9 (n-9) unsaturated fatty acids, on neutrophils and the relevance of these effects for disease development are discussed.
Gago, Gabriela; Diacovich, Lautaro; Arabolaza, Ana; Tsai, Shiou-Chuan; Gramajo, Hugo
All organisms that produce fatty acids do so via a repeated cycle of reactions. In mammals and other animals, these reactions are catalyzed by a type I fatty acid synthase (FAS), a large multifunctional protein to which the growing chain is covalently attached. In contrast, most bacteria (and plants) contain a type II system in which each reaction is catalyzed by a discrete protein. The pathway of fatty acid biosynthesis in Escherichia coli is well established and has provided a foundation for elucidating the type II FAS pathways in other bacteria (White et al., 2005). However, fatty acid biosynthesis is more diverse in the phylum Actinobacteria: Mycobacterium, possess both FAS systems while Streptomyces species have only the multi-enzyme FAS II system and Corynebacterium species exclusively FAS I. In this review we present an overview of the genome organization, biochemical properties and physiological relevance of the two FAS systems in the three genera of actinomycetes mentioned above. We also address in detail the biochemical and structural properties of the acyl-CoA carboxylases (ACCases) that catalyzes the first committed step of fatty acid synthesis in actinomycetes, and discuss the molecular bases of their substrate specificity and the structure-based identification of new ACCase inhibitors with anti-mycobacterial properties. PMID:21204864
Wadhwani, Nisha S; Narang, Ankita S; Mehendale, Savita S; Wagh, Girija N; Gupte, Sanjay A; Joshi, Sadhana R
The present prospective study examines proportions of maternal erythrocyte fatty acids across gestation and their association with cord erythrocyte fatty acids in normotensive control (NC) and preeclamptic pregnancies. We hypothesize that maternal fatty acid status in early pregnancy influences fetal fatty acid stores in preeclampsia. 137 NC women and 58 women with preeclampsia were included in this study. Maternal blood was collected at 3 time points during pregnancy (16-20th weeks, 26-30th weeks and at delivery). Cord blood was collected at delivery. Fatty acids were analyzed using gas chromatography. The proportions of maternal erythrocyte α-linolenic acid, docosahexaenoic acid, nervonic acid, and monounsaturated fatty acids (MUFA) (p < 0.05 for all) were lower while total n-6 fatty acids were higher (p < 0.05) at 16-20th weeks of gestation in preeclampsia as compared with NC. Cord 18:3n-3, 22:6n-3, 24:1n-9, MUFA, and total n-3 fatty acids (p < 0.05 for all) were also lower in preeclampsia as compared with NC. A positive association was observed between maternal erythrocyte 22:6n-3 and 24:1n-9 at 16-20th weeks with the same fatty acids in cord erythrocytes (p < 0.05 for both) in preeclampsia. Our study for the first time indicates alteration in maternal erythrocyte fatty acids at 16th weeks of gestation which is further reflected in cord erythrocytes at delivery in preeclampsia.
Ghasemi Fard, Samaneh; Linderborg, Kaisa M; Turchini, Giovanni M; Sinclair, Andrew J
Based on the results from a human study which showed significantly reduced incorporation of DPA compared with EPA into chylomicrons, this study was designed to test if dietary DPA was significantly less absorbed than EPA. Male Sprague Dawley rats were randomly assigned to three groups of six, and were fed a semi-synthetic high fat diet (23.5% fat) for 9 days. The test omega 3 fatty acids (EPA and DPA, 250mg/animal/day, free fatty acid form) or olive oil (250mg/animal/day) were added to the high fat diet on days 5, 6 and 7. Dietary EPA and DPA appeared in the faeces on days 6, 7 and 8, with the total amount of DPA excreted being 4.6-fold greater than that of EPA. The total amount of faecal fat did not differ significantly between the groups. At the conclusion of the study (day 9), it was found that liver DPA, EPA and total n-3 LC-PUFA levels were significantly increased by both DPA and EPA feeding compared with the olive oil fed control group. In the heart, DPA feeding increased the DPA content and both DPA and EPA feeding increased the total n-3 LC-PUFA levels. This study showed that DPA and EPA, both provided in free form, are metabolised differently, despite being chemically similar.
Jurczyszyn, Artur; Czepiel, Jacek; Gdula-Argasińska, Joanna; Czapkiewicz, Anna; Biesiada, Grażyna; Dróżdż, Mirosław; Perucki, William; Castillo, Jorge J
Mounting data show that fatty acids (FA) and fatty acid synthase (FAS) function could be potential targets for multiple myeloma (MM) therapy. Our study aimed at comparing the FA composition of erythrocyte membranes of MM patients and healthy controls. MM patients had higher saturated FA and n-6 polyunsaturated FA (PUFA) and lower monounsaturated, n-3 PUFA and trans-FA indices than controls. The n-3/n-6 PUFA ratio was lower in MM patients and there was distinct clustering of variants of individual FA in MM patients. The FA content of erythrocyte membrane could serve as a diagnostic and/or predictive biomarker in MM.
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 t...
Innis, S M; Novak, E M; Keller, B O
Considerable information has accumulated to show that DHA and EPA have unique roles that differ from other n-3 fatty acids and the n-6 fatty acids, with increasing understanding of the mechanisms through which these fatty acids reduce risk of disease. DHA and EPA regulate hepatic lipid and glucose metabolism, but are present in foods of animal origin, which are generally high in protein with variable triglycerides and low carbohydrate. Biological activity at intakes too low to provide significant amounts of energy is consistent with the definition of a vitamin for which needs are modified by life-stage, diet and genetic variables, and disease. Recent studies reveal that DHA may play a central role in co-coordinating complex networks that integrate hepatic glucose, fatty acid and amino acid metabolism for the purpose of efficient utilization of dietary protein, particularly during early development when the milk diet provides large amounts of energy from fat.
Özcan, Mustafa; Demirel, Gulcan; Yakan, Akın; Ekiz, Bülent; Tölü, Cemil; Savaş, Türker
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.
Patarra, R F; Leite, J; Pereira, R; Baptista, J; Neto, A I
The content of total lipids and the fatty acid (FA) profile were determined for eight macroalgae (Cystoseira abies-marina, Fucus spiralis, Chaetomorpha pachynema, Codium elisabethae, Porphyra sp., Osmundea pinnatifida, Pterocladiella capillacea and Sphaeroccoccus coronopifolius). Total lipids were extracted using a solvent mixture of methanol/chloroform (2/1, v/v) and further derivatised to FA methyl esters (FAME). The analyses of FAME samples were performed by gas chromatography coupled to a flame ionisation detector. The total lipid content ranged from 0.06 to 3.54 g (per 100 g). The most abundant saturated FA were palmitic (C16:0) and myristic (C14:0), while oleic (C18:1 n-9) was the dominant monounsaturated acid. All seaweeds contained linoleic FA (C18:2 n-6). The α-linolenic (C18:3 n-3) and eicosapentaenoic (20:5 n-3) acids were present only in Porphyra sp. (3.34% ± 0.13) and C. pachynema (0.47% ± 0.12), respectively. The n-6/n-3 and h/H ratios were low, suggesting a high nutritional value of the algae studied.
Dysregulation of adipokines is a hallmark of obesity. Polyunsaturated (n3) fatty acids in fish oil may exert anti-inflammatory effects on adipose tissue mitigating the dysregulation of adipokines thereby preventing obesity. This study investigated the effects of high-fat diets containing different...
OMEGA-3 FATTY ACIDS DURING PREGNANCY S HARE W ITH W OMEN OMEGA-3 FATTY ACIDS DURING PREGNANCY During pregnancy, your baby gets most ... eat and vitamins you take. Omega-3 fatty acids (omega-3s) are an important family of building ...
Lee, R M
A proper balance between the n-3 and n-6 series of essential fatty acids (EFAs) is essential for homeostasis and normal growth in humans. Dietary supplement with fish oil and related n-3 EFAs has been used to study their antihypertensive property in animals and humans with borderline and essential hypertension. In the animal models, chronic treatment of young animals generally only attenuated the development of hypertension. In animals with hypercholesterolemia, n-3 EFA supplement increased the incidence of atherosclerosis. In humans, chronic treatment with fish oil only produced a small reduction in blood pressure. The concerns are that the high dose of fish oil may interfere with the control of blood glucose in diabetic patients, and may cause prolonged bleeding in surgical patients. Studies on the animal models of hypertension showed that n-6 EFAs are more effective than n-3 EFAs in lowering and normalizing the blood pressure of these animals, probably through the production of tissue prostaglandins, which favour vasodilation. The antihypertensive effect of the n-6 EFAs in humans is not well known, because there are only a few studies, usually involving a very small number of patients. A possible side effects of n-6 EFAs for concern is that they might stimulate tumour development. A careful examination of these risk factors is needed before any recommendation can be made concerning the use of EFAs for the control of hypertension for humans.
Clarke, S D; Turini, M; Jump, D B; Abraham, S; Reedy, M
Polyunsaturated fatty acids (PUFA) of the (n-6) and (n-3) families inhibit the rate of gene transcription for a number of hepatic lipogenic and glycolytic genes, e.g., fatty acid synthase (FAS). In contrast, saturated and monounsaturated fatty acids have no inhibitory capability. The suppression of gene transcription resulting from the addition of PUFA to a high carbohydrate diet: occurs quickly (< 3 h) after its addition to a high glucose diet; can be recreated with hepatocytes cultured in a serum-free medium containing insulin and glucocorticoids; can be demonstrated in diabetic rats fed fructose; and is independent of glucagon. While the nature of the intracellular PUFA inhibitor is unclear, it appears that delta-6 desaturation is a required step in the process. Recently, the fatty acid activated nuclear factor, peroxisome-proliferator activated receptor (PPAR) was suggested to be the PUFA-response factor. However, the potent PPAR activators ETYA and Wy-14643 did not suppress hepatic expression of FAS, but did induce the PPAR-responsive gene, acyl-CoA oxidase (AOX). Similarly, treating rat hepatocytes with 20:4 (n-6) suppressed FAS expression but had no effect on AOX. Thus, it appears that the PUFA regulation of gene transcription involves a PUFA-response factor that is independent from PPAR.
Somerville, Chris; van de Loo, Frank
The present invention relates to the identification of nucleic acid sequences and constructs, and methods related thereto, and the use of these sequences and constructs to produce genetically modified plants for the purpose of altering the composition of plant oils, waxes and related compounds.
Mazalli, Mônica R; Bragagnolo, Neura
A comparative study between two methods (lipid extraction followed by saponification and methylation, and direct methylation) to determine the fatty acids in egg yolk was evaluated. Direct methylation of the samples resulted in lower fatty acid content and greater variation in the results than the lipid extraction followed by saponification and methylation. The low repeatability observed for the direct HCl methylation method was probably due to a less efficient extraction and conversion of the fatty acids into their methyl esters as compared to the same procedure starting with the lipid extract. As the lipid extraction followed by esterification method was shown to be more precise it was validated using powdered egg certified as reference material (RM 8415, NIST) and applied to samples of egg, egg enriched with polyunsaturated omega-3 fatty acids (n-3 PUFA), and commercial spray-dried whole egg powder.
Very-long-chain highly unsaturated C28 fatty acids (HUFAs), found in a number of dinoflagellates, are released as methyl esters from phospholipids obtained by fractionation of lipid extracts. By contrast, the highly unsaturated C18 fatty acid octadecapentaenoic acid (18:5n-3), co...
Little information is available on effect of cooking on beneficial fatty acids such as conjugated linoleic acid (CLA) and n-3 polyunsaturated fatty acids (PUFA). The objective of this study was to examine impact of cooking on the FA composition of ground lamb of two different muscles. Samples were p...
Raclot, T; Oudart, H
During lipolysis, adipose tissue triacylglycerols (TAG) undergo concurrent breakdown and synthesis because some of the newly hydrolysed and released non-esterified ('free') fatty acids (NEFA) can subsequently be taken up and re-esterified. The present study examines whether and how the release of individual fatty acids is affected by the re-uptake of some of the newly hydrolysed fatty acids in vitro during lipolysis. To alter fatty acid release and re-uptake, adipose tissue fragments and isolated adipocytes from rats were incubated under various conditions, i.e. several cell concentrations or adipose fragment quantities, with or without glucose. In the various conditions tested, the NEFA/glycerol molar ratio ranged from 1.5 to 2.9. Whatever the incubation conditions, including those resulting in very low, medium or high fatty acid re-uptake (as assessed by the NEFA/glycerol ratio), the percentage weight of fatty acids in NEFA was significantly different from that in TAG for 20-24 of the 35 fatty acids that were considered. Thus the greater the fatty acid re-uptake, the higher the proportion of polyunsaturated fatty acids and the lower the proportion of long-chain saturated and monounsaturated fatty acids in NEFA. Moreover, the relative mobilization (%NEFA/%TAG) of the least readily mobilized fatty acid (C(22:1,n-11)) was 6.2-fold lower than that of the most readily mobilized fatty acid (C(20:5,n-3)) under conditions of very low fatty acid re-uptake, and 14.8-fold lower under conditions of high fatty acid re-uptake, indicating a widening of the range of relative mobilizations. We conclude that the composition of the NEFA pool is affected by the rate of fatty acid re-uptake. This provides strong evidence for the selective re-uptake of adipose tissue fatty acids during lipolysis. PMID:10794723
Woodcock, Steven R; Bonacci, Gustavo; Gelhaus, Stacy L; Schopfer, Francisco J
Nitrated fatty acids are the product of nitrogen dioxide reaction with unsaturated fatty acids. The discovery of peroxynitrite and peroxidase-induced nitration of biomolecules led to the initial reports of endogenous nitrated fatty acids. These species increase during ischemia/reperfusion, but concentrations are often at or near the limits of detection. Here, we describe multiple methods for nitrated fatty acid synthesis and sample extraction from complex biological matrices and a rigorous method of qualitative and quantitative detection of nitrated fatty acids by liquid chromatography-mass spectrometry. In addition, optimized instrument conditions and caveats regarding data interpretation are discussed.
Woodcock, Steven R.; Bonacci, Gustavo; Gelhaus, Stacy L.; Schopfer, Francisco J.
Nitrated fatty acids are the product of nitrogen dioxide reaction with unsaturated fatty acids. The discovery of peroxynitrite and peroxidase-induced nitration of biomolecules led to the initial reports of endogenous nitrated fatty acids. These species increase during ischemia reperfusion, but concentrations are often at or near the limits of detection. Here, we describe multiple methods for nitrated fatty acid synthesis, sample extraction from complex biological matrices, and a rigorous method of qualitative and quantitative detection of nitrated fatty acids by LC-MS. In addition, optimized instrument conditions and caveats regarding data interpretation are discussed. PMID:23200809
Prepartum maternal diets supplemented with oilseeds alter the fatty acid profile in bovine neonatal plasma possibly through reduced placental expression of fatty acid transporter protein 4 and fatty acid translocase.
Salehi, Reza; Ambrose, Divakar J
In the present study, we determined the effects of maternal dietary fat and the type of fat on plasma fatty acids and the expression of placental fatty acid transporter genes. In Experiment 1, Holstein cows in the last 35 days of gestation received diets containing sunflower seed (n=8; high in linoleic acid (LA)), canola seed (n=7; high in oleic acid (OLA)) or no oilseed (n=7; control). Fatty acids were quantified in dam and neonate plasma at calving. In Experiment 2, placental cotyledons were collected (LA: n=4; OLA: n=4; control: n=5) to quantify gene expression. Maternal long-chain polyunsaturated fatty acids, neonatal total n-3 fatty acids and eicosapentaenoic acid (EPA) declined, whereas docosahexaenoic acid (DHA) and total fat tended to decline following fat supplementation prepartum. Feeding of LA versus OLA prepartum tended to increase peroxisome proliferator-activated receptor α (PPARA) expression, whereas peroxisome proliferator-activated receptor δ (PPARD) and peroxisome proliferator-activated receptor γ (PPARG) expression tended to be higher in OLA- than LA-fed cows. Expression of fatty acid transporter protein 4 (FATP4) and fatty acid translocase (FAT/CD36) expression was lower in placental tissue of cows fed fat compared with control cows. Reduced total n-3 fatty acids, EPA and DHA in neonates born of dams fed fat prepartum is likely due to changes in PPARs and reduced expression of placental FATP4 and FAT/CD36.
Srivastava, P.C.; Knapp, F.F. Jr.; Kabalka, G.W.
Radiolabeled long-chain fatty acids have diagnostic value as radiopharmaceutical tools in myocardial imaging. Some applications of these fatty acids are limited due to their natural metabolic degradation in vivo with subsequent washout of the radioactivity from the myocardium. The identification of structural features that will increase the myocardial residence time without decreasing the heart uptake of long-chain fatty acids is of interest. Fatty acids containing the tellurium heteroatom were the first modified fatty acids developed that show unique prolonged myocardial retention and low blood levels. Our detailed studies with radioiodinated vinyliodide substituted tellurium fatty acids demonstrate that heart uptake is a function of the tellurium position. New techniques of tellurium and organoborane chemistry have been developed for the synthesis of a variety of radioiodinated iodoalkenyl tellurium fatty acids. 9 refs., 3 figs., 2 tabs.
Vasconi, Mauro; Caprino, Fabio; Bellagamba, Federica; Busetto, Maria Letizia; Bernardi, Cristian; Puzzi, Cesare; Moretti, Vittorio Maria
In this study, the proximate and fatty acid compositions of the muscle tissue of 186 samples of fish belonging to fifteen species of freshwater fish harvested in subalpine lakes (bleak, shad, crucian carp, whitefish, common carp, pike, black bullhead, burbot, perch, Italian roach, roach, rudd, wels catfish, chub and tench) were investigated. Most of the fish demonstrated a lipid content in the fillet lower than 2.0 g 100 g(-1) wet weight (range 0.6-9.7). A strong relationship between feeding behavior and fatty acid composition of the muscle lipids was observed. Planktivorous fish showed the lowest amounts of n-3 fatty acids (p < 0.05), but the highest monounsaturated fatty acid (MUFA) contents, in particular 18:1n-9. Conversely, carnivorous fish showed the highest amounts of saturated fatty acids and n-3 fatty acids (p < 0.05), but the lowest MUFA contents. Omnivorous fish showed substantial proportions of n-3 fatty acids and the highest contents of n-6 fatty acids. Principal component analysis showed a distinct separation between fish species according to their feeding habits and demonstrated that the most contributing trophic markers were 18:1n-9, 18:3n-3, 22:6n-3 and 20:4n-6. The quantitative amounts n-3 polyunsaturated fatty acid in muscle tissues varied depending on the fish species, the lipid content and the feeding habits. Some species were very lean, and therefore would be poor choices for human consumption to meet dietary n-3 fatty acid requirements. Nevertheless, the more frequently consumed and appreciated fish, shad and whitefish, had EPA and DHA contents in the range 900-1,000 mg 100 g(-1) fresh fillet.
Igarashi, Miki; Gao, Fei; Kim, Hyung-Wook; Ma, Kaizong; Bell, Jane M.; Rapoport, Stanley I.
Few studies have examined effects of feeding animals a diet deficient in n-6 polyunsaturated fatty acids (PUFAs) but with an adequate amount of n-3 PUFAs. To do this, we fed post-weaning male rats a control n-6 and n-3 PUFA adequate diet and an n-6 deficient diet for 15 weeks, and measured stable lipid and fatty acid concentrations in different organs. The deficient diet contained nutritionally essential linoleic acid (LA,18:2n-6) as 2.3% of total fatty acids (10% of the recommended minimum LA requirement for rodents) but no arachidonic acid (AA, 20:4n-6), and an adequate amount (4.8% of total fatty acids) of α-linolenic acid (18:3n-3). The deficient compared with adequate diet did not significantly affect body weight, but decreased testis weight by 10%. AA concentration was decreased significantly in serum (−86%), brain (−27%), liver (−68%), heart (−39%), testis (−25%), and epididymal adipose tissue (−77%). Eicosapentaenoic (20:5n-3) and docosahexaenoic acid (22:6n-3) concentrations were increased in all but adipose tissue, and the total monounsaturated fatty acid concentration was increased in all organs. The concentration of 20:3n-9, a marker of LA deficiency, was increased by the deficient diet, and serum concentrations of triacylglycerol, total cholesterol and total phospholipid were reduced. In summary, 15 weeks of dietary n-6 PUFA deficiency with n-3 PUFA adequacy significantly reduced n-6 PUFA concentrations in different organs of male rats, while increasing n-3 PUFA and monounsaturated fatty acid concentrations. This rat model could be used to study metabolic, functional and behavioral effects of dietary n-6 PUFA deficiency. PMID:19073280
Carter, R N; Schmidt, J M
The cellular fatty acid composition of 14 strains of Caulobacter speices and types, two species of Prosthecomicrobium, and two species of Asticcacaulis was determined by gas-liquid chromatography. In most of these bacteria, the major fatty acids were octadecenoic acid (C18:1), hexadecenoic acid (C16:1) and hexadecanoic acid (C16:0). Some cyclopropane and branched chain fatty acids were detected in addition to the straight chained acids. Hydroxytetradecanoic acid was an important component of P.enhydrum but significant amounts of hydroxy acids were not detected in other prosthecate bacteria examined.
Uppala, Radha; Dudiak, Brianne; Beck, Megan E; Bharathi, Sivakama S; Zhang, Yuxun; Stolz, Donna B; Goetzman, Eric S
The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse the mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders.
Gibson, R A; Neumann, M A; Lien, E L; Boyd, K A; Tu, W C
The conversion of the plant-derived omega-3 (n-3) α-linolenic acid (ALA, 18:3n-3) to the long-chain eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) can be increased by ALA sufficient diets compared to ALA deficient diets. Diets containing ALA above an optimal level result in no further increase in DHA levels in animals and humans. The present study evaluates means of maximizing plasma DHA accumulation by systematically varying both linoleic acid (LA, 18:2n-6) and ALA dietary level. Weanling rats were fed one of 54 diets for three weeks. The diets varied in the percentage of energy (en%) of LA (0.07-17.1 en%) and ALA (0.02-12.1 en%) by manipulating both the fat content and the balance of vegetable oils. The peak of plasma phospholipid DHA (>8% total fatty acids) was attained as a result of feeding a narrow dietary range of 1-3 en% ALA and 1-2 en% LA but was suppressed to basal levels (∼2% total fatty acids) at dietary intakes of total polyunsaturated fatty acids (PUFA) above 3 en%. We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA is low (<3 en%).
Henry, Susan A.; Keith, Alec D.
Dietary saturated fatty acids containing 12- to 18-carbon atoms satisfy growth requirements of Neurospora crassa mutant cel (previously named ol; Perkins et al., reference 11); unsaturated fatty acids are synthesized by direct desaturation when an appropriate saturate is available. Odd-chain saturates, 15 carbons and 17 carbons long, satisfy the requirement, and elaidic acid (18:1 Δ9trans) results in slow growth. Oleic acid and other cis-unsaturated fatty acids do not satisfy growth requirements; however, oleic acid plus elaidic acid result in growth at a faster rate than elaidate alone. The use of a spin-label fatty acid reveals that hyphae produced by cel during a slow basal level of growth have lipids that reflect a relatively rigid state of viscosity compared to wild type. cel Supplemented with fatty acids and wild type supplemented in the same way have lipids of the same viscosities as reflected by electron spin resonance. PMID:4323964
Calder, Philip C
Inflammation underlies many common conditions and diseases. Fatty acids can influence inflammation through a variety of mechanisms, including acting via cell surface and intracellular receptors/sensors that control inflammatory cell signalling and gene expression patterns. Some effects of fatty acids on inflammatory cells appear to be mediated by, or at least are associated with, changes in fatty acid composition of cell membranes. Changes in these compositions can modify membrane fluidity, lipid raft formation, cell signalling leading to altered gene expression, and the pattern of lipid and peptide mediator production. Cells involved in the inflammatory response are typically rich in the n-6 fatty acid arachidonic acid, but the contents of arachidonic acid and of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be altered through oral administration of EPA and DHA. Eicosanoids produced from arachidonic acid have roles in inflammation. EPA also gives rise to eicosanoids and these may have differing properties from those of arachidonic acid-derived eicosanoids. EPA and DHA give rise to resolvins which are anti-inflammatory and inflammation resolving. Thus, fatty acid exposure and the fatty acid composition of human inflammatory cells influences their function. As a result of their anti-inflammatory actions marine n-3 fatty acids have therapeutic efficacy in rheumatoid arthritis, although benefits in other inflammatory diseases and conditions have not been unequivocally demonstrated. The anti-inflammatory effects of marine n-3 fatty acids may contribute to their protective actions towards atherosclerosis, plaque rupture and cardiovascular mortality. The therapeutic dose of n-3 fatty acids is not clear.
Zlatanos, Spiros; Laskaridis, Kostas; Feist, Christian; Sagredos, Angelos
Proximate composition, fatty acid analysis and protein digestibility-corrected amino acid score (PDCAAS) in three commercially important cephalopods of the Mediterranean sea (cuttlefish, octopus and squid) were determined. The results of the proximate analysis showed that these species had very high protein:fat ratios similar to lean beef. Docosahexaenoic, palmitic and eicosipentaenoic acid were the most abundant fatty acids among analyzed species. The amount of n-3 fatty acids was higher than that of saturated, monounsaturated and n-6 fatty acids. Despite the fact that cephalopods contain small amounts of fat they were found quite rich in n-3 fatty acids. Finally, PDCAAS indicated that these organisms had a very good protein quality.
Dewhurst, R J; Scollan, N D; Lee, M R F; Ougham, H J; Humphreys, M O
The declining consumption of ruminant products has been partly associated with their high proportion (but not necessarily content) of saturated fatty acids. Recent studies have focused on the less prominent fact that they are also important sources of beneficial fatty acids, including n-3 fatty acids and conjugated linoleic acids. alpha-Linolenic acid (18 : 3n-3) is of particular interest because it also contributes to improved flavour of beef and lamb. Many recent studies showed large effects of special concentrates on levels of fatty acids in milk and meat. However, the 'rumen protection' treatments, needed to ensure a worthwhile level of fatty acid in products, are expensive. Herbage lipids are the cheapest and safest source of these fatty acids and so breeding to increase delivery of fatty acids from plants into ruminant products is an important long-term strategy. Plant lipids usually contain high levels of polyunsaturated fatty acids, particularly 18 : 2n-6 and 18 : 3n-3 which are the precursors of beneficial fatty acids. Whilst some plants are particularly rich in individual fatty acids (e.g. 18 : 3n-3 in linseed), there are also useful levels in grass and clover (Trifolium Spp.). Levels of fatty acids in forages in relation to species and varieties are considered, as well as management and conservation methods. Relationships between levels of fatty acids and existing traits and genetic markers are identified. The effects of forage treatments on the fatty acid content of ruminant products are reviewed. The higher levels of polyunsaturated fatty acids in milk from cows fed clover silages show that the level of fatty acids in herbage is not the only factor affecting levels of fatty acids in ruminant products. Further effort is needed to characterise susceptibility of unsaturated fatty acids to oxidative loss during field wilting and biohydrogenation losses in the rumen, and the relative importance of plant and microbial processes in these losses. The pathways
Meneses, Flávia; Torres, Alexandre G; Trugo, Nádia M F
The aims of the present study were to evaluate essential fatty acids (EFA) and long-chain PUFA (LCPUFA) status in lactating adolescents and its association with breast milk composition. Healthy nursing adolescents from Rio de Janeiro, Brazil (n 30; 14-19 years; 30-120 d postpartum), exclusively or predominantly breast-feeding, participated in this study. Breast milk and blood samples were collected after overnight fasting. Fatty acid composition of breast milk, erythrocyte membrane (EM) and plasma NEFA were determined by GC. Indices of fatty acid status (mean melting point (MMP); EFA status index; DHA status indices, 22 : 5n-6:22 : 4n-6 and 22 : 6n-3:22 : 5n-6 ratios) were calculated from EM fatty acid composition. Dietary intake of n-3 fatty acids was low when compared with current recommendations for lactating women. MMP was associated with indices of DHA status, some individual fatty acids in EM and years post-menarche and weeks postpartum, suggesting the use of erythrocyte MMP as a possible comprehensive biochemical marker of LCPUFA status in this physiological condition. The DHA status of lactating adolescents and their milk DHA concentrations were similar to the values of Brazilian lactating adults, but lower compared with the values of lactating adults from other countries. Therefore, these lactating adolescents were apparently not disadvantaged, as compared with the Brazilian adults, when EM and breast milk fatty acid composition were considered. In general, PUFA in milk from adolescents presented few associations with their concentrations in plasma NEFA and with maternal status. However, milk DHA was associated with maternal LCPUFA and DHA states.
Laseter, J. L.; Lawler, G. C.; Walkinshaw, C. H.; Weete, J. D.
The total fatty constituents of slash pine (Pinus elliottii) tissue cultures, seeds, and seedlings were examined by GLC and MS. Qualitatively, the fatty acid composition of these tissues was found to be very similar to that reported for other pine species. The fatty acid contents of the tissue cultures resembled that of the seedling tissues. The branched-chain C(sub 17) acid reported for several other Pinus species was confirmed as the anteiso isomer.
The fatty acid profile of kenaf (Hibiscus cannabinus L.) seed oil has been the subject of several previous reports in the literature. These reports vary considerably regarding the presence and amounts of specific fatty acids, notably epoxyoleic acid but also cyclic (cyclopropene and cyclopropane) fa...
Studies in enterally-fed infants have shown a positive effect of n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementatin on neurodevelopment. The effect of n-3 LCPUFA in fish oil-based parenteral (PN) lipid emulsions on neuronal tissues of PN-fed preterm infants is unknown. The objective ...
Beare-Rogers, J L; Gray, L M; Hollywood, R
Fifty brands of margarine were analysed for cis-polyunsaturated acids by lipoxidase, for trans fatty acid by infared spectroscopy, and for fatty acid composition by gas-liquid chromatography. High concentrations of trans fatty acids tended to be associated with low concentrations of linoleic acid. Later analyses on eight of the brands, respresenting various proportions of linoleic to trans fatty acids, indicated that two of them contained still higher levels of trans fatty acids (greater than 60%) and negligible amounts of linoleic acid. It is proposed that margarine could be a vehicle for the distribution of some dietary linoleic acid and that the level of linoleic acid and the summation of the saturated plus trans fatty acids be known to ascertain nutritional characteristics.
Wood, J D; Enser, M; Fisher, A V; Nute, G R; Sheard, P R; Richardson, R I; Hughes, S I; Whittington, F M
This paper reviews the factors affecting the fatty acid composition of adipose tissue and muscle in pigs, sheep and cattle and shows that a major factor is the total amount of fat. The effects of fatty acid composition on meat quality are also reviewed. Pigs have high levels of polyunsaturated fatty acids (PUFA), including the long chain (C20-22) PUFA in adipose tissue and muscle. The full range of PUFA are also found in sheep adipose tissue and muscle whereas cattle 'conserve' long chain PUFA in muscle phospholipid. Linoleic acid (18:2n-6) is a major ingredient of feeds for all species. Its incorporation into adipose tissue and muscle in relation to the amount in the diet is greater than for other fatty acids. It is deposited in muscle phospholipid at a high level where it and its long chain products eg aracidonic acid (20:4n-6) compete well for insertion into phospholipid molecules. Its proportion in pig adipose tissue declines as fat deposition proceeds and is an index of fatness. The same inverse relationships are not seen in ruminant adipose tissue but in all species the proportion of 18:2n-6 declines in muscle as fat deposition increases. The main reason is that phospholipid, where 18:2n-6 is located, declines as a proportion of muscle lipid and the proportion of neutral lipid, with its higher content of saturated and monounsaturated fatty acids, increases. Oleic acid (18:1cis-9), formed from stearic acid (18:0) by the enzyme stearoyl Co-A desaturase, is a major component of neutral lipid and in ruminants the same enzyme forms conjugated linoleic acid (CLA), an important nutrient in human nutrition. Like 18:2n-6, α-linolenic acid (18:3n-3) is an essential fatty acid and is important to ruminants since it is the major fatty acid in grass. However it does not compete well for insertion into phospholipid compared with 18:2n-6 and its incorporation into adipose tissue and muscle is less efficient. Greater biohydrogenation of 18:3n-3 and a long rumen transit time
Tworek; Muti; Micheli; Krogh; Riboli; Berrino
PURPOSE: Menopausal status effects female anatomical functioning at a variety of system-wide and cellular levels, including cellular membrane composition. This study analyzed a nested case-control ORDET data set of 433 pre and post-menopausal breast cancer controls to examine the effects of menopausal status on the fatty acid composition of the red blood cell membrane.METHODS: ORDET is a prospective cohort study conducted in Italy to investigate the etiologic role of hormones and diet in breast cancer development. The fatty acid composition was measured and analyzed by gas chromotography, comparing retention time with standard measurement. Twenty-two individual fatty acids were measured, recorded, and categorized into four fatty acid groups: saturated, monounsaturated, polyunsaturated n-6 (PUFA n-6), and polyunsaturated (PUFA n-3) fatty acids.RESULTS: Post-menopausal women had consistently lower mean values for all four fatty acid categories and all individual fatty acids. Statistically significant mean differences, by menopausal status, were observed for three of the four fatty acid categories: saturated fatty acids (p = 0.006), PUFA n-6 acids (p = 0.001), and PUFA n-3 acids (p = 0.000). The biggest statistically significant differences in mean values among individual fatty acids for each category were observed for Palmitic acid (p = 0.009), Oleic acid (p = 0.040), Linoleic acid (p = 0.000), and Docosahexaenoic acid (p = 0.000). Individual fatty acids were also less highly correlated among post-menopausal women.CONCLUSIONS: There was an observed relationship between menopausal status and the fatty acid composition of the red blood cell membrane that warrants further study. This relationship may contribute to the physiological and psychological changes that occur during and after menopause, and may have far-reaching implications for women's health.
Bascuñán, Karla A.; Valenzuela, Rodrigo; Chamorro, Rodrigo; Valencia, Alejandra; Barrera, Cynthia; Puigrredon, Claudia; Sandoval, Jorge; Valenzuela, Alfonso
Chilean diets are characterized by a low supply of n-3 polyunsaturated fatty acids (n-3 PUFA), which are critical nutrients during pregnancy and lactation, because of their role in brain and visual development. DHA is the most relevant n-3 PUFA in this period. We evaluated the dietary n-3 PUFA intake and erythrocyte phospholipids n-3 PUFA in Chilean pregnant women. Eighty healthy pregnant women (20–36 years old) in the 3rd–6th month of pregnancy were included in the study. Dietary assessment was done applying a food frequency questionnaire, and data were analyzed through the Food Processor SQL® software. Fatty acids of erythrocyte phospholipids were assessed by gas-liquid chromatography. Diet composition was high in saturated fat, low in mono- and PUFA, high in n-6 PUFA (linoleic acid) and low in n-3 PUFA (alpha-linolenic acid and DHA), with imbalance in the n-6/n-3 PUFA ratio. Similar results were observed for fatty acids from erythrocyte phospholipids. The sample of Chilean pregnant women showed high consumption of saturated fat and low consumption of n-3 PUFA, which is reflected in the low DHA content of erythrocyte phospholipids. Imbalance between n-6/n-3 PUFA could negatively affect fetal development. New strategies are necessary to improve n-3 PUFA intake throughout pregnancy and breast feeding periods. Furthermore, it is necessary to develop dietary interventions to improve the quality of consumed foods with particular emphasis on n-3 PUFA. PMID:25386693
... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sucrose fatty acid esters. 172.859 Section 172.859... CONSUMPTION Multipurpose Additives § 172.859 Sucrose fatty acid esters. Sucrose fatty acid esters identified...) Sucrose fatty acid esters are the mono-, di-, and tri-esters of sucrose with fatty acids and are...
... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sucrose fatty acid esters. 172.859 Section 172.859... CONSUMPTION Multipurpose Additives § 172.859 Sucrose fatty acid esters. Sucrose fatty acid esters identified...) Sucrose fatty acid esters are the mono-, di-, and tri-esters of sucrose with fatty acids and are...
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sucrose fatty acid esters. 172.859 Section 172.859... CONSUMPTION Multipurpose Additives § 172.859 Sucrose fatty acid esters. Sucrose fatty acid esters identified...) Sucrose fatty acid esters are the mono-, di-, and tri-esters of sucrose with fatty acids and are...
... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fatty acids test system. 862.1290 Section 862.1290....1290 Fatty acids test system. (a) Identification. A fatty acids test system is a device intended to measure fatty acids in plasma and serum. Measurements of fatty acids are used in the diagnosis...
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fatty acids test system. 862.1290 Section 862.1290....1290 Fatty acids test system. (a) Identification. A fatty acids test system is a device intended to measure fatty acids in plasma and serum. Measurements of fatty acids are used in the diagnosis...
... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sucrose fatty acid esters. 172.859 Section 172.859... CONSUMPTION Multipurpose Additives § 172.859 Sucrose fatty acid esters. Sucrose fatty acid esters identified...) Sucrose fatty acid esters are the mono-, di-, and tri-esters of sucrose with fatty acids and are...
Choi, Anna L; Mogensen, Ulla B.; Bjerve, Kristian S.; Debes, Frodi; Weihe, Pal; Grandjean, Philippe; Budtz-Jørgensen, Esben
Background Methylmercury, a worldwide contaminant of fish and seafood, can cause adverse effects on the developing nervous system. However, long-chain n-3 polyunsaturated fatty acids in seafood provide beneficial effects on brain development. Negative confounding will likely result in underestimation of both mercury toxicity and nutrient benefits unless mutual adjustment is included in the analysis. Methods We examined these associations in 176 Faroese children, in whom prenatal methylmercury exposure was assessed from mercury concentrations in cord blood and maternal hair. The relative concentrations of fatty acids were determined in cord serum phospholipids. Neuropsychological performance in verbal, motor, attention, spatial, and memory functions was assessed at 7 years of age. Multiple regression and structural equation models (SEMs) were carried out to determine the confounder-adjusted associations with methylmercury exposure. Results A short delay recall (in percent change) in the California Verbal Learning Test (CVLT) was associated with a doubling of cord blood methylmercury (−18.9, 95% confidence interval [CI] = −36.3, −1.51). The association became stronger after the inclusion of fatty acid concentrations in the analysis (−22.0, 95% confidence interval [CI] = −39.4, −4.62). In structural equation models, poorer memory function (corresponding to a lower score in the learning trials and short delay recall in CVLT) was associated with a doubling of prenatal exposure to methylmercury after the inclusion of fatty acid concentrations in the analysis (−1.94, 95% CI = −3.39, −0.49). Conclusions Associations between prenatal exposure to methylmercury and neurobehavioral deficits in memory function at school age were strengthened after fatty acid adjustment, thus suggesting that n-3 fatty acids need to be included in analysis of similar studies to avoid underestimation of the associations with methylmercury exposure. PMID:24561639
TCDD appeared to interfere with fatty acid metabolism leading to an increase in unsaturation. Furthermore, Andersen et al. (2) proposed that such an...increase in cellular unsaturated fatty acids may lead-to excessive membrane fluidity (as indicated by induced changes in red blood cell fragility) and...TASK WORK UNITELEMENT NO. NO. NO. NO. 11. TITLE (include Security Claificati on) ~/~. Cellular Effects of Perfluorinated Fatty Ac ds 12. PERSONAL
Merdzhanova, Albena; Ivanov, Ivaylo; Dobreva, Diana A.; Makedonski, Lyubomir
This article presents information about omega-3 (h-3) and omega-6 (n-6) polyunsaturated fatty acid (PUFA) contents in a broad range of commercially important fish species available on Bulgarian fish markets. The aim is to raise consumers' awareness and encourage them to eat fish. Fish species from the Black Sea coast have relatively high proportion of n-3 PUFAs, of which more than 80% is by EPf (eicosapentaenoic acid, C 20:5 n-3) and DHA (docosahexaenoic acid, C 22:6 n-3). Extensive epidemiological studies show that fish consumption is inversely associated with the incidence of cardiovascular diseases (CVD), stroke and the functioning of the brain. About 0.5 g of omega-3 (EPA+DHA) a day or two savings of oily fish a week are required to reduce the risk of death from CVD. PUFAs needs should be satisfied not only with food additives but with fish lipids containing food.
Xue, Shan; He, Zhifei; Lu, Jingzhi; Tao, Xiaoqi; Zheng, Li; Xie, Yuejie; Xiao, Xia; Peng, Rong; Li, Hongjun
The changes in fatty acid composition of total intramuscular lipid and phospholipids were investigated in the longissimus dorsi, left-hind leg muscle, and abdominal muscle of male Ira rabbits. Changes were monitored at 35, 45, 60, 75, and 90 d. Analysis using gas chromatography identified 21 types of fatty acids. Results showed that the intramuscular lipid increased and the intramuscular phospholipids (total intramuscular lipid %) decreased in all muscles with increasing age (p<0.05). An abundant amount of unsaturated fatty acids, especially polyunsaturated fatty acids, was distributed in male Ira rabbits at different ages and muscles. Palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2), and arachidonic acid (C20:4) were the major fatty acids, which account to the dynamic changes of the n-6/n-3 value in Ira rabbit meat.
... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acids, tall-oil, reaction... Fatty acids, tall-oil, reaction products with modified fatty acids and polyalkanolamines (generic). (a... generically as fatty acids, tall-oil, reaction products with modified fatty acids and polyalkanolamines (PMN...
... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acids, tall-oil, reaction... Fatty acids, tall-oil, reaction products with modified fatty acids and polyalkanolamines (generic). (a... generically as fatty acids, tall-oil, reaction products with modified fatty acids and polyalkanolamines (PMN...
Uppala, Radha; McKinney, Richard W; Brant, Kelly A; Fabisiak, James P; Goetzman, Eric S
Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation-the pathway by which fatty acids are catabolized for energy-in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with l-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 h), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis.
In the search of value-added products from surplus soybean oil, we produced many new hydroxy fatty acids through microbial bioconversion. Hydroxy fatty acids are used in a wide range of industrial products, such as resins, waxes, nylons plastics, lubricants, cosmetics, and additives in coatings and...
Uppala, Radha; McKinney, Richard W.; Brant, Kelly A.; Fabisiak, James P.; Goetzman, Eric S.
Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation—the pathway by which fatty acids are catabolized for energy—in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with L-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 hr), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. PMID:26051273
Fatty acids are basic renewable chemical building blocks that can be used as intermediates for a multitude of products. Today the global value of fatty acids exceeds 18 billion dollars and is expected to increase to nearly 26 billion over the period from 2014-2019. From it auspicious beginnings, the...
Geerts, Roy; Kuijer, Patrick; van Ginkel, Cornelis G; Plugge, Caroline M
To get insight in the biodegradation and potential read-across of fatty acid amides, N-[3-(dimethylamino)propyl] cocoamide and N-(1-ethylpiperazine) tall oil amide were used as model compounds. Two bacteria, Pseudomonas aeruginosa PK1 and Pseudomonas putida PK2 were isolated with N-[3-(dimethylamino)propyl] cocoamide and its hydrolysis product N,N-dimethyl-1,3-propanediamine, respectively. In mixed culture, both strains accomplished complete mineralization of N-[3-(dimethylamino)propyl] cocoamide. Aeromonas hydrophila PK3 was enriched with N-(1-ethylpiperazine) tall oil amide and subsequently isolated using agar plates containing dodecanoate. N-(2-Aminoethyl)piperazine, the hydrolysis product of N-(1-ethylpiperazine) tall oil amide, was not degraded. The aerobic biodegradation pathway for primary and secondary fatty acid amides of P. aeruginosa and A. hydrophila involved initial hydrolysis of the amide bond producing ammonium, or amines, where the fatty acids formed were immediately metabolized. Complete mineralization of secondary fatty acid amides depended on the biodegradability of the released amine. Tertiary fatty acid amides were not transformed by P. aeruginosa or A. hydrophila. These strains were able to utilize all tested primary and secondary fatty acid amides independent of the amine structure and fatty acid. Read-across of previous reported ready biodegradability results of primary and secondary fatty acid amides is justified based on the broad substrate specificity and the initial hydrolytic attack of the two isolates PK1 and PK3.
Peng, Kun-Tao; Zheng, Cun-Ni; Xue, Jiao; Chen, Xiao-Yan; Yang, Wei-Dong; Liu, Jie-Sheng; Bai, Weibin; Li, Hong-Ye
Microalgae are important primary producers in the marine ecosystem and excellent sources of lipids and other bioactive compounds. The marine diatom Phaeodactylum tricornutum accumulates eicosapentaenoic acid (EPA, 20:5n-3) as its major component of fatty acids. To improve the EPA production, delta 5 desaturase, which plays a role in EPA biosynthetic pathway, was characterized in P. tricornutum. An annotated delta 5 desaturase PtD5b gene was cloned and overexpressed in P. tricornutum. The transgene was integrated into the genome demonstrated by Southern blot, and the overexpression of PtD5b was verified by qPCR and Western blot analysis. Fatty acid composition exhibited a significant increase in the unsaturated fatty acids. Monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) showed an increase of 75% and 64%, respectively. In particular, EPA showed an increase of 58% in engineered microalgae. Meanwhile, neutral lipid content showed an increase up to 65% in engineered microalgae. More importantly, engineered cells showed a similar growth rate with the wild type, thus keeping high biomass productivity. This work provides an effective way to improve the production of microalgal value-added bioproducts by metabolic engineering.
Davis, Brenda C; Kris-Etherton, Penny M
Although vegetarian diets are generally lower in total fat, saturated fat, and cholesterol than are nonvegetarian diets, they provide comparable levels of essential fatty acids. Vegetarian, especially vegan, diets are relatively low in alpha-linolenic acid (ALA) compared with linoleic acid (LA) and provide little, if any, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Clinical studies suggest that tissue levels of long-chain n-3 fatty acids are depressed in vegetarians, particularly in vegans. n-3 Fatty acids have numerous physiologic benefits, including potent cardioprotective effects. These effects have been demonstrated for ALA as well as EPA and DHA, although the response is generally less for ALA than for EPA and DHA. Conversion of ALA by the body to the more active longer-chain metabolites is inefficient: < 5-10% for EPA and 2-5% for DHA. Thus, total n-3 requirements may be higher for vegetarians than for nonvegetarians, as vegetarians must rely on conversion of ALA to EPA and DHA. Because of the beneficial effects of n-3 fatty acids, it is recommended that vegetarians make dietary changes to optimize n-3 fatty acid status.
Jeromson, Stewart; Gallagher, Iain J; Galloway, Stuart D R; Hamilton, D Lee
Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle.
Stillman, M A; Maibach, H I; Shalita, A R
Free fatty acids of human skin surface lipids have previously been implicated in the pathogenesis of acne vulgaris because of their apparent irritant and comedogenic properties. Prior studies on the relative irritancy of free fatty acids revealed the saturated C8 to C14 fatty acids and a C18 dienoic unsaturated fatty acid (linoleic) to be most irritating. Saturated free fatty acids from C3 to C18, and unsaturated C18 free fatty acids were applied daily under occlusive patch tests to human skin until detectable erythema appeared. The most irritating fatty acids were C8 through C12. Of the unsaturated fatty acids tested, only linoleic acid produced irritation.
Bühner, S; Nagel, E; Körber, J; Vogelsang, H; Linn, T; Pichlmayr, R
In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls the fatty acid distribution in the inflamed ileal mucosa was significantly characterised by (a) a decrease of 18:2 n6 and 18:3 n3 accompanied by a substantial increase of the highly polyunsaturated fatty acids 20:4 n6, 22:4 n6, and 22:6 n3 and (b) a higher unsaturation index of total fatty acids compared with controls. These changes were similar in the inflamed colon. Additionally, both the inflamed and the macroscopically normal colonic mucosa showed an increase of saturated (18:0) and a decrease of monounsaturated fatty acids (18:1 n9). Fatty acid profiles of ileum and colon showed side variations in controls, but not in the Crohn's disease group. These data suggest that in Crohn's disease changes in the distribution of polyunsaturated fatty acids seem to be the general feature of inflamed mucosa in small and large intestine. Results further suggest that colonic fatty acid metabolism in Crohn's disease is altered by degrees, showing changes in saturated and monounsaturated fatty acids as an additional, primary event. PMID:7959199
Freese, Riitta; Korkalo, Liisa; Vessby, Bengt; Tengblad, Siv; Vaara, Elina M; Hauta-alus, Helena; Selvester, Kerry; Mutanen, Marja
Many African diets are low in fat but are currently changing because of nutrition transition. We studied fat and fatty acid (FA) intake and the essential fatty acid (EFA) status of adolescent girls (aged 14-19 years, n 262) in Zambezia Province, central Mozambique. A cross-sectional study was carried out in a city as well as in the towns and rural villages of a coastal and an inland district. Dietary intake and FA sources were studied in a 24 h dietary recall. FA compositions of cholesteryl esters and phospholipids of non-fasting serum samples were analysed by GLC. Fat intake was low (13-18 % of energy) in all areas. Coconut and palm oil were the main sources of fat, and soyabean oil and maize were the main sources of PUFA. Compared to Food and Agriculture Organization/WHO 2010 recommendations, intake of linoleic acid (LA, 18 : 2n-6) was inadequate in the coastal district, and intakes of n-3 PUFA were inadequate in all areas. FA compositions of serum lipids differed between areas. The proportions of LA tended to be highest in the city and lowest in the rural areas. The phospholipid mead (20 : 3n-9):arachidonic acid (20 : 4n-6) ratio did not indicate EFA insufficiency. LA proportions in phospholipids were low, but those of long-chain n-6 and n-3 PUFA were high in comparison with Western adolescents. To conclude, fat sources, FA intake and EFA status differed between adolescent girls living in different types of communities. Fat intake was low, but EFA insufficiency was not indicated.