Ω3 Polyunsaturated Fatty Acids Research Articles

Contrasting effects of arachidonic acid and docosahexaenoic acid membrane incorporation into cardiomyocytes on free cholesterol turnover

The preservation of a constant pool of free cholesterol (FC) is critical to ensure several functions of cardiomyocytes. We investigated the impact of the membrane incorporation of arachidonic acid (C20:4 ω6, AA) or docosahexaenoic acid (C22:6 ω3, DHA) as ω6 or ω3 polyunsaturated fatty acids (PUFAs) on cholesterol homeostasis in primary cultures of neonatal rat cardiac myocytes. We measured significant alterations to the phospholipid FA profiles, which had markedly different ω6/ω3 ratios between the AA and DHA cells (13 vs. 1). The AA cells showed a 2.7-fold lower cholesterol biosynthesis than the DHA cells. Overall, the AA cells showed 2-fold lower FC masses and 2-fold higher cholesteryl ester masses than the DHA cells. The AA cells had a lower FC to phospholipid ratio and higher triglyceride levels than the DHA cells. Moreover, the AA cells showed a 40% decrease in ATP binding cassette transporter A1 (ABCA1)-mediated and a 19% decrease in ABCG1-mediated cholesterol efflux than the DHA cells. The differences in cholesterol efflux pathways induced by AA or DHA incorporation were not caused by variations in ABCs transporter expression and were reduced when ABC transporters were overexpressed by exposure to LXR/RXR agonists. These results show that AA incorporation into cardiomyocyte membranes decreased the FC turnover by markedly decreasing the endogenous cholesterol synthesis and by decreasing the ABCA1- and ABCG1-cholesterol efflux pathways, whereas DHA had the opposite effects. We propose that these observations may partially contribute to the beneficial effects on the heart of a diet containing a high ω3/ω6 PUFA ratio.

Inhibitory effect of a novel combination of Salvia hispanica (chia) seed and Punica granatum (pomegranate) fruit extracts on melanin production

In recent years, dietary fatty acids have been extensively evaluated for nutritional as well as cosmetic benefits. Among the dietary fats, the omega-3 (ω3) and omega-6 (ω6) forms of polyunsaturated fatty acids (PUFAs) have been found to exhibit many biological functions in the skin such as prevention of transepidermal water loss, maintenance of the stratum corneum epidermal barrier, and disruption of melanogenesis in epidermal melanocytes. In this study, we examined the effect of chia seed extract, high in ω3 (linolenic acid) and ω6 (linoleic acid) PUFAs, for its capacity to affect melanogenesis. Chia seed extract was shown to inhibit melanin biosynthesis in Melan-a cells; however, linoleic and α-linolenic acids alone did not effectively reduce melanin content. Further investigation demonstrated that chia seed extract in combination with pomegranate fruit extract had a synergistic effect on the inhibition of melanin biosynthesis with no corresponding effect on tyrosinase activity. Investigation of the possible mechanism of action revealed that chia seed extract downregulated expression of melanogenesis-related genes (Tyr, Tyrp1, and Mc1r), alone and in combination with pomegranate fruit extract, suggesting that the inhibition of melanin biosynthesis by a novel combination of chia seed and pomegranate fruit extracts is possibly due to the downregulation of gene expression of key melanogenic enzymes.

Complex processing of lipids from liver of the gonatid squid <i>Berryteuthis magister </i>

Berryteuthis magister is one of the most common commercial species in the North-West Pacific, but its liver never was utilized before, though it was a rich source of the lipids with simple ether links, 1- О -alkyl-glycerol ethers (АGE), and ω3 polyunsaturated fatty acids (ω3 PUFA). Technology for complex processing of lipids from its liver is developed and presented in details. These forms of lipids are distinguished by a wide range of biologic activity: AGE are effective immunomodulators which enhance hemopoiesis, relieve lesions and lower risk of secondary lesions under radio-therapy and can be used for treatment of some malignant tumors (glioma, prostate cancer, lung carcinoma, etc.); ω3 PUFA could be used for prophylactic of cardiovascular diseases, Alzheimer’s sclerosis, senile dementia, skin diseases (protein synthesis control) and other diseases. The presented technology provides extraction of three preparations with different chemical composition and pharmacological activity. Both saturated and unsaturated AGE could be extracted using the property of different solubility in organic solvents for different components of the mixture of hydrolyzed lipids. The main component of the saturated AGE fraction is chimyl alcohol (90.5 %), but the unsaturated fraction contains 54.7 % of monounsaturated AGE. The ω3 PUFA are concentrated to summary 46 % content of eicosapentaenoic acid and docosahexaenoic acid by the method of fatty acids crystallization with carbamide. Comparing with traditional raw materials for АGE and ω3 PUFA production, as shark liver, the liver of gonatid squid is more suitable because of its high and accessible resources, whereas sharks are presented in bycatch only so cannot be considered as a stable source.

Abstract P191: Erythrocyte Polyunsaturated Fatty Acid, Weight Gain, and Risk of Becoming Overweight in Middle-aged and Older Women

Background: Laboratory studies suggest that ω3 and ω6 polyunsaturated fatty acids (PUFA) may have divergent effects on the development of obesity. Epidemiologic studies comparing the associations for ω3 and ω6 PUFA are limited. Objective: We prospectively examined whether the baseline proportions of ω3 and ω6 PUFAs on erythrocyte membranes were associated with the risk of becoming overweight and changes in body weight in the Women’s Health Study (WHS). Methods: We identified WHS participants in a previous nested case-control study of hypertension who reported a body mass index (BMI) <25 kg/m 2 at baseline. Baseline fatty acid (FA) composition of erythrocyte membranes was measured as biomarkers of dietary FA intake using gas chromatography. Women who subsequently reported a BMI ≥25 kg/m 2 during follow-up were defined as becoming overweight. Body weight change was calculated as the difference in reported body weight from baseline to annual follow-up questionnaires. Results: Among 534 women with baseline BMI <25 kg/m 2 , 186 became overweight during an average of 10 years of follow-up. After initial adjustment for age, race, randomized treatment, the hazard ratios (HR) and 95% confidence interval (95% CI) for becoming overweight across increasing quartiles of erythrocyte PUFA were 1.00, 0.77 (0.49-1.21), 1.12 (0.75-1.67), and 1.19 (0.79-1.77) for cis ω6 PUFA (p, trend: 0.31), 1.00, 0.90 (0.61-1.31), 0.76 (0.51-1.13), 0.71 (0.45-1.10) for cis ω3 PUFA (p, trend: 0.09), and 1.00, 1.37 (0.84-2.22), 1.57 (1.01-2.43), and 1.58 (1.01-2.46) for ω6 to ω3 PUFA ratio (p, trend: 0.046). Additional adjustment for lifestyle and dietary factors did not substantially attenuate these associations, with HR (95% CI) of 1.00, 1.26 (0.76-2.08), 1.44 (0.91-2.28), and 1.56 (0.97-2.51) across increasing quartiles of ω6 to ω3 PUFA ratio (p, trend: 0.064). Analysis of longitudinal change in body weight showed similar associations. After multivariable adjustment, the mean±standard error of weight gain over an average of 10 years of follow-up across increasing quartiles of erythrocyte PUFA were 2.34±0.49, 1.92±0.53, 2.86±0.54, and 3.10±0.53 kg for cis ω6 PUFA (p, trend: 0.04), 2.97±0.52, 2.60±0.53, 2.74±0.53, 2.16±0.51 kg for cis ω3 PUFA (p, trend: 0.095), and 2.13±0.51, 2.65±0.54, 2.77±0.53, 2.98±0.52 kg for ω6 to ω3 PUFA ratio (p, trend: 0.05). trans PUFA 18:2 was not associated with the risk of becoming overweight or longitudinal weight gain. Analyses of joint categories of ω3 and ω6 PUFA did not show significant interaction . Conclusion: In this prospective study, we found suggestive evidence that the proportion of cis ω6 PUFA on erythrocyte membrane was positively associated, and cis ω3 PUFA inversely associated, with the risk of becoming overweight and weight gain in initially normal-weight women.

Cold-induced gene expression and ω3 fatty acid unsaturation is controlled by red light in Synechocystis

The expression of cold-induced genes, which are controlled by the cold sensor histidine kinase Hik33, and the formation of ω3 polyunsaturated fatty acids are controlled by light in the cyanobacterium Synechocystis sp. PCC 6803. Cold-induced Hik33-dependent gene expression is initiated by red light (∼700nm), but not by blue or green light. Red light also turns on the ω3 fatty acid desaturation. Different combinations of other wavelengths in red spectral region (635 and 726nm) had no effect on the red-light-activated cold-induced transcription or fatty acid desaturation. Therefore, the involvement of phytochrome-like photoreceptor(s), similar to phytochromes of higher plants, in this regulation was not confirmed. The absence of light-dependence of gene expression in the mutant cells deficient in Hik33 suggests the involvement of this histidine kinase in direct or mediated with red light regulation of cold responses in Synechocystis.

Composition, volatile profiles and functional properties of virgin olive oils produced by two-phase vs three-phase centrifugal decanters

The present study was designed to compare the impact of a two- vs a three-phase decanter on the quality parameters, sterols, fatty acids, terpenes, phenolic compounds and volatile compounds, as well as antiradical activity of the obtained oils. Moreover, serum lipid antioxidant capacity and anti-inflammatory potential in human mononuclear cells were tested as more biologically relevant assays than the chemical radical scavenging assays. Results show that the cold pressed olive oils obtained from both technologies were of the extra virgin quality. Peroxide values were significantly lower in two-phase decanter samples, while ω6 polyunsaturated fatty acids were higher in two- vs three-phase samples. The significantly higher phenolics content in oil produced by two- vs three-phase centrifuge was attributed to higher hydroxytyrosol, as well as to higher tyrosol, vanillin and homovanillic alcohol levels. Evaluation of the effect of centrifuge system on oils' functional properties showed a clear superiority of two-phase decanter samples as to health maintenance, as these exerted higher ferric reducing capacity, elongation of serum lipid lag time and decrease in cytokine response of stimulated human mononuclear cells, compared to those from three-phase decanter. The two-phase oil samples contained more volatile aroma compounds and more C5–C6 alcohols and aldehydes.

The PNPLA3 Ile148Met interacts with overweight and dietary intakes on fasting triglyceride levels

The Ile148Met (rs738409, G-allele) in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) associates with liver fat content and may lead to loss-of-function (hydrolysis) or gain-of-function (CoA-dependent lysophosphatidic acid acyltransferase) defects. PNPLA3 is up-regulated by dietary carbohydrates, and interactions between rs738409 and carbohydrates, and sugar and ω6:ω3-polyunsaturated fatty acid (PUFA) ratio on hepatic fat accumulation have been reported. We examined interaction between rs738409 and overweight, and between rs738409 and dietary intakes (carbohydrates, sucrose and ω6:ω3-PUFA ratio), on fasting triglyceride levels. From the Malmo Diet and Cancer Study-Cardiovascular Cohort, 4,827 individuals without diabetes aged 58 ± 6 years, 2,346 with BMI ≤ 25 kg/m2 and 2,478 with BMI > 25 kg/m2, were included in cross-sectional analyses. Dietary data were collected by a modified diet history method. Overweight modified the association between rs738409 and fasting triglyceride levels (P interaction = 0.003). G-allele associated with lower triglycerides only among overweight individuals (P = 0.01). Nominally, significant interaction on triglyceride levels was observed between rs738409 and sucrose among normal-weight individuals (P interaction = 0.03). G-allele associated with lower triglycerides among overweight individuals in the lowest tertiles of carbohydrate and ω6:ω3-PUFA ratio (P = 0.04 and P = 0.001) and with higher triglycerides among normal-weight individuals in the highest tertile of sucrose (P = 0.001). We conclude that overweight and dietary sucrose may modify the association between rs738409 and fasting triglyceride levels.Electronic supplementary materialThe online version of this article (doi:10.1007/s12263-014-0388-4) contains supplementary material, which is available to authorized users.

Modulation of T-type calcium channels by bioactive lipids

T-type calcium channels (T-channels/CaV3) have unique biophysical properties allowing a calcium influx at resting membrane potential of most cells. T-channels are ubiquitously expressed in many tissues and contribute to low-threshold spikes and burst firing in central neurons as well as to pacemaker activities in cardiac cells. They also emerged as potential targets to treat cancer and hypertension. Regulation of these channels appears complex, and several studies have indicated that CaV3.1, CaV3.2, and CaV3.3 currents are directly inhibited by multiple endogenous lipids independently of membrane receptors or intracellular pathways. These bioactive lipids include arachidonic acid and ω3 poly-unsaturated fatty acids; the endocannabinoid anandamide and other N-acylethanolamides; the lipoamino-acids and lipo-neurotransmitters; the P450 epoxygenase metabolite 5,6-epoxyeicosatrienoic acid; as well as similar molecules with 18-22 carbons in the alkyl chain. In this review, we summarize evidence for direct effects of these signaling molecules, the molecular mechanisms underlying the current inhibition, and the involved chemical features. The impact of this modulation in physiology and pathophysiology is discussed with a special emphasis on pain aspects and vasodilation. Overall, these data clearly indicate that T-current inhibition is an important mechanism by which bioactive lipids mediate their physiological functions.

Littoral invertebrates in waders’ nutrition at migratory stopover sites in the Azov and Black Sea region

Seasonal migration for birds – distant migrants are the most energy intensive. Fat reserves accumulated in the bird’s body before migration and during migratory stopovers determine success of the long-distance flight. Lipids play a vital role both as a source of energy and as structural components of cell membranes. For most migrants to the speed and quality processes fat accumulation affects the feed ration in the field of migration stops. Fodder saturation with essential polyunsaturated fatty acids (PUFAs) is of great importance. Being paramount for physiological processes, these acids cannot be synthesized in the bird’s body. The proposed article is dedicated to the study of waders’ trophic relationships with their prey items, and the use of PUFAs as biochemical markers. This approach is based on the specificity of the fatty acids contained in the lipids of invertebrate to be used as food bird species studied. Significant amount NPZHK waders obtained from forage that can be considered PUFAs as biochemical markers to determine the range and diversity of food producing birds PUFAs ways, and also to study the food chain in ecosystems. A fatty acid spectrum (FAS) of the lipids common for nine littoral invertebrate species (Gammarus aequicauda, Idotea balthica, Artemia salina, Nerеis sp., Nerеis zonata, Theodoxces astrachanicus, Hydrobia acuta, Chironomus salinarius, Chironomus plumosus), which constitute the main component of waders’ diet at the migratory stopover sites in the Azov and Black Sea region, has been studied. Found that the largest amount of total lipids contained in Nereis zonata (4,6 %) and Artemia salina (4,4 %), the lowest amount of total lipids was observed in Chironomus (1,5–1,8 %), which implies that polychaete worms and Artemia salina, as a source of fat, are the most productive for waders. Our research has found that mollusks, polychaete worms, and Artemia salina are the most effective waders’ fodder in the PUFAs content. Mollusks contain the largest amount of PUFAs, their spectrum is ω3 and ω6 PUFAs, especially arаchidonic acid C20:4. Polychate worms are also characterized by a high PUFAs level; they serve for birds as a source of linolenic and linoleic acid groups. Artemia salina contains a large amount of eicosapentaenoic С20:5ω3 and docosahexaenoic С22:6ω3 acids, which getting to an organism of birds, participating in the formation of cell membranes, act as thermal stabilizer lipid bilayers, enhance stamina during long-distance flight. A high abundance of Artemia salina in the feeding areas permit tundra waders to use them as a prey item, which can fulfill the bird’s body with a required amount of fatty acids in a short time. We have established an influence of some environmental factors, as water temperature and salinity, on the lipids FAS of littoral invertebrates. Spectrum analysis of polyene fatty acids in the lipids closely related species of invertebrates living in different salinity water showed that the content of PUFAs in the lipid depend on their food spectrum, and the environmental conditions. Therefore, anthropogenic pressure and changes of water hydrological regime may affect PUFAs content in the lipids of littoral invertebrates. In its turn, this factor may change alimentary behavior and migratory strategy of the birds, which use migratory stopover sites in the region in question. Shallow waters of the Azov-Black Sea region are characterized by different climatic characteristics and a large reserve of phytoplankton. This explains the mass character species studied of invertebrates to feeding areas and their use as basic prey items, many species of waders.

Interactions Between the Dietary Polyunsaturated Fatty Acid Ratio and Genetic Factors Determine Susceptibility to Pediatric Crohn's Disease

Increased dietary ratios of ω6/ω3 polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease (CD), but epidemiologic data are limited. We investigated whether variants of genes that control polyunsaturated fatty acid metabolism (CYP4F3, FADS1, and FADS2), along with the dietary ratio of ω6/ω3, confers susceptibility to CD. Based on data from 182 children newly diagnosed with CD and 250 controls, we found that children who consumed a higher dietary ratio of ω6/ω3 were susceptible for CD if they were also carriers of specific variants of CYP4F3 and FADS2 genes. Our findings implicate diet-gene interactions in the pathogenesis of CD.

Fatty Acid composition and levels of selected polyunsaturated Fatty acids in four commercial important freshwater fish species from lake victoria, Tanzania.

Fatty acids (FAs) particularly ω3 and ω6 polyunsaturated fatty acids (PUFAs) play important role in human health. This study aimed to investigate the composition and levels of selected ω3 PUFAs in four commercial fish species, Nile perch (Lates niloticus), Nile tilapia (Oreochromis niloticus), Tilapia zillii, and dagaa (Rastrineobola argentea) from Mwanza Gulf in Lake Victoria. The results indicated that 36 types of FAs with different saturation levels were detected. These FAs were dominated by docosahexaenoic (DHA), eicosapentaenoic (EPA), docosapentaenoic (DPA), and eicosatetraenoic acids. O. niloticus had the highest composition of FAs (34) compared to L. niloticus (27), T. zillii (26), and R. argentea (21). The levels of EPA differed significantly among the four commercial fish species (F = 6.19, P = 0.001). The highest EPA levels were found in R. argentea followed by L. niloticus and O. niloticus and the lowest in T. zillii. The DPA levels showed no significant difference among the four fish species studied (F = 0.652, P = 0.583). The study concluded that all four commercial species collected from Mwanza Gulf are good for human health, but R. argentea is the best for consumption because it contains higher levels of ω3 FAs, mainly EPA.

Omega-3 PUFA supplementation differentially affects behavior and cognition in the young and aged non-human primate Grey mouse lemur (Microcebus murinus)

Data are divergent about the ability of dietary ω3 fatty acids to prevent age-associated cognitive decline. Most of the clinical trials failed to demonstrate a protective effect of ω3 fatty acids against cognitive decline and methodological issues are still under debate. Conversely to human studies, experiments performed in adult rodents clearly indicate that long chain ω3 fatty acids play a beneficial role in behavioral and cognitive functions. Inconsistent observations between human and rodent studies highlight the importance of the use of non-human primate models. We recently started a series of experiments on Grey mouse lemurs, an emerging non-human primate model of aging in order to assess the impact of ω3 fatty acids dietary supplementation on several brain functions. These experiments started with the determination of the fatty acids composition of target organs (brain, adipose tissue, liver, plasma) of animals fed under control diet. We then explored the impact of ω3 polyunsaturated fatty acids (PUFA) supplementation on cognition and behavior in young and aged grey mouse lemurs. The aim of the present review is to compare the observations made in young and aged grey mouse lemurs and to explore the possibilities of new experiments in order to bridge the gap between rodents and Humans.

Brain Protection Therapy for Ischemic Brain Injury

Therapeutic strategies for protecting the brain against ischemic injury aim to salvage the ischemic penumbra or to expand the therapeutic time window, or both. We have investigated the protective effects of several agents using a rat model of transient focal cerebral ischemia. Our experimental studies have identified the following agents with attractive protective mechanisms against brain ischemia: the free-radical scavenger edaravone (MCI-186), the immunosuppressant tacrolimus (FK506), bone marrow stromal cells (BMSCs) /bone marrow mononuclear cells (BMMCs), the ω3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), and the hydroxymethyl glutaryl coenzyme A reductase inhibitor atorvastatin. The free-radical scavenger MCI-186 has a Bax/Bcl-2-dependent antiapoptotic mechanism in a rat model of transient focal cerebral ischemia. The therapeutic time window for FK506 in rat transient focal ischemia is from 60 to 120 minutes after ischemia induction, and mild hypothermia (35°C) expands the therapeutic time window up to 120 minutes after ischemia induction. Intravenous transplantation of BMSCs 120 minutes after ischemia induction, which is out of the therapeutic time window for FK506 alone, is neuroprotective when performed in conjunction with FK506 injection. Intra-arterial transplantation of BMMCs is more protective against transient focal cerebral ischemia than is intravenous transplantation of BMMCs. Repeated intravenous transplantation of BMMCs achieves further neuroprotection against ischemic brain injury. Pretreatment with ethyl-EPA inhibits endothelial Rho-kinase activation and reduces tissue oxidative stress following transient ischemia, resulting in strong neuroprotection. The long-term protective effects of atorvastatin against brain ischemia require continuous oral administration after ischemia/reperfusion. All of the agents used in our experimental studies are established therapies for ischemic stroke or other disorders. Further investigations are needed before such experimental brain protection strategies can be applied clinically.

Tracking Diet Preferences of Bats Using Stable Isotope and Fatty Acid Signatures of Faeces

Stable isotope and fatty acid signatures of biomaterials can provide important information about the dietary niche of animals. Stable isotope and fatty acid signatures differ between aquatic and terrestrial food webs, and therefore can be used to assess the aquatic and terrestrial contributions to the diets of species. We studied faecal samples of three co-occurring bat species with known differences in feeding preferences. The aim was to assess whether stable isotope and fatty acid signatures of faeces can be used to determine feeding preferences. We used bat faeces because they can be easily and non-invasively collected. We hypothesised that faeces stable isotope and fatty acid signatures will reveal the terrestrial, aquatic and mixed feeding niches of Myotis myotis, M. daubentonii, and M. mystacinus, respectively. As predicted, the faeces of M. myotis were characterized by higher δ 13C values and higher concentrations of linoleic acid and total ω6 polyunsaturated fatty acids (PUFAs), which are typically higher in terrestrial food webs. The faeces of M. daubentonii had higher δ 15Ν values and higher concentrations of docosahexaenoic acid and total ω3 PUFAs, characteristic features of aquatic systems. Myotis mystacinus faeces had intermediate δ 15Ν values and concentrations of both types of fatty acids. Our results show that analysing stable isotope and/or fatty acid signatures of faeces provides a promising, non-invasive tool to study the feeding ecology of bats and to assess aquatic-terrestrial interactions.

Unsaturated Fatty Acids Disrupt Smad Signaling in Gonadotrope Cells Leading to Inhibition of FSHβ Gene Expression

Reproductive function is highly dependent on nutritional input. We recently provided evidence that the unsaturated ω6 fatty acid (FA), linoleic acid (linoleic), interferes with transcription and secretion of the gonadotropin LH, highlighting the existence of a lipid sensing in pituitary gonadotropes. Here, we show, using a combination of in vivo and in vitro models, that linoleic differentially regulates Lhb and Fshb expression. Central exposure of rats to linoleic over 7 days was associated with increase of Lhb but not Fshb transcript levels. Consistently, exposure of rat pituitary cells or LβT2 cells to linoleic increased Lhb, whereas it dramatically decreased Fshb transcript levels without affecting its stability. This effect was also induced by ω9 and ω3-polyunsaturated FA but not by saturated palmitic acid. Analysis of the underlying mechanisms in LβT2 cells using small interfering RNA revealed that early growth response protein 1 mediates linoleic stimulation of Lhb expression. Furthermore, we demonstrated that linoleic counteracts activin and bone morphogenetic protein-2 stimulation of Fshb expression. Using Western blotting and Smad-responsive reporter gene assays, linoleic was shown to decrease basal Smad2/3 phosphorylation levels as well as activin- and bone morphogenetic protein-2-dependent activation of Smad, uncovering a new FA-sensitive signaling cascade. Finally, the protein phosphatase magnesium-dependent 1A was shown to mediate linoleic inhibition of basal Smad phosphorylation and Fshb expression, identifying protein phosphatase magnesium-dependent 1A as a new target of FA in gonadotropes. Altogether, this study provides a novel mechanism by which FAs target gene expression and underlines the relevant role of pituitary gonadotropes in mediating the effects of nutritional FA on reproductive function.

Stable Isotope and Signature Fatty Acid Analyses Suggest Reef Manta Rays Feed on Demersal Zooplankton

Assessing the trophic role and interaction of an animal is key to understanding its general ecology and dynamics. Conventional techniques used to elucidate diet, such as stomach content analysis, are not suitable for large threatened marine species. Non-lethal sampling combined with biochemical methods provides a practical alternative for investigating the feeding ecology of these species. Stable isotope and signature fatty acid analyses of muscle tissue were used for the first time to examine assimilated diet of the reef manta ray Manta alfredi, and were compared with different zooplankton functional groups (i.e. near-surface zooplankton collected during manta ray feeding events and non-feeding periods, epipelagic zooplankton, demersal zooplankton and several different zooplankton taxa). Stable isotope δ15N values confirmed that the reef manta ray is a secondary consumer. This species had relatively high levels of docosahexaenoic acid (DHA) indicating a flagellate-based food source in the diet, which likely reflects feeding on DHA-rich near-surface and epipelagic zooplankton. However, high levels of ω6 polyunsaturated fatty acids and slightly enriched δ13C values in reef manta ray tissue suggest that they do not feed solely on pelagic zooplankton, but rather obtain part of their diet from another origin. The closest match was with demersal zooplankton, suggesting it is an important component of the reef manta ray diet. The ability to feed on demersal zooplankton is likely linked to the horizontal and vertical movement patterns of this giant planktivore. These new insights into the habitat use and feeding ecology of the reef manta ray will assist in the effective evaluation of its conservation needs.

Tocopherols in Seafood and Aquaculture Products

Fish products contain various nutritionally beneficial components, namely, ω3-polyunsaturated fatty acids (ω3-PUFA), minerals, and vitamins. Particularly, tocopherols (α-, β-, γ-, and δ-tocopherol) can be provided by seafood and aquaculture products. Hence, this review shows the various aspects of tocopherols in seafood and aquaculture products. For tocopherol determination in these products, HPLC methods coupled with diode array detection in the UV area of the spectrum or fluorescence detection have been shown as sensitive and accurate. These newest methods have helped in understanding tocopherols fate upon ingestion by seafood organisms. Tocopherols pass through the intestinal mucosa mainly by the same passive diffusion mechanism as fats. After absorption, the transport mechanism is thought to consist of two loops. The first loop is dietary, including chylomicrons and fatty acids bound to carrier protein, transporting lipids mainly to the liver. The other is the transport from the liver to tissues and storage sites. Moreover, tocopherol levels in fish organisms correlate with diet levels, being adjusted in fish body depending on diet concentration. For farmed fish species, insufficient levels of tocopherols in the diet can lead to poor growth performance or to nutritional disease. The tocopherol quantity needed as a feed supplement depends on various factors, such as the vitamer mixture, the lipid level and source, the method of diet preparation, and the feed storage conditions. Other ingredients in diet may be of great importance, it has been proposed that α-tocopherol may behave as a prooxidant synergist at higher concentrations when prooxidants such as transition metals are present. However, the antioxidant action of tocopherols outweighs this prooxidant effect, provided that adequate conditions are used. In fact, muscle-based foods containing higher levels of tocopherol show, for instance, higher lipid stability. Besides, tocopherols are important not only from the nutritional point of view but also from the physiological one, since they are involved in many metabolic processes in the human organism. Moreover, synergistic interactions with selenium and ascorbic acid have been reported. It deserves attention that there is evidence tocopherols taken with food can prevent heart disease, while no such evidence was found for α-tocopherol as supplement. From this perspective, eating fish is advisable, since, for instance, a 100 g serving of salmon may provide nearly 14% of recommended dietary allowance.

ω3-PUFAs Exert Anti-Inflammatory Activity in Visceral Adipocytes from Colorectal Cancer Patients

ObjectiveThe aim of this study was to correlate specific fatty acid profiles of visceral white adipose tissue (WAT) with inflammatory signatures potentially associated with colorectal cancer (CRC).MethodsHuman adipocytes were isolated from biopsies of visceral WAT from 24 subjects subdivided in four groups: normal-weight (BMI 22.0-24.9 Kg/m2) and over-weight/obese (BMI 26.0-40.0 Kg/m2), affected or not by CRC. To define whether obesity and/or CRC affect the inflammatory status of WAT, the activation of the pro-inflammatory STAT3 and the anti-inflammatory PPARγ transcription factors as well as the expression of adiponectin were analyzed by immunoblotting in adipocytes isolated from each group of subjects. Furthermore, to evaluate whether differences in inflammatory WAT environment correlate with specific fatty acid profiles, gas-chromatographic analysis was carried out on WAT collected from all subject categories. Finally, the effect of the ω3 docosahexaenoic acid treatment on the balance between pro- and anti-inflammatory factors in adipocytes was also evaluated.ResultsWe provide the first evidence for the existence of a pro-inflammatory environment in WAT of CRC patients, as assessed by the up-regulation of STAT3, and the concomitant decrease of PPARγ and adiponectin with respect to healthy subjects. WAT inflammatory status was independent of obesity degree but correlated with a decreased ω3-/ω6-polyunsaturated fatty acid ratio. These observations suggested that qualitative changes, other than quantitative ones, in WAT fatty acid may influence tissue dysfunctions potentially linked to inflammatory conditions. This hypothesis was further supported by the finding that adipocyte treatment with docosahexaenoic acid restored the equilibrium between STAT3 and PPARγ.ConclusionOur results suggest that adipocyte dysfunctions occur in CRC patients creating a pro-inflammatory environment that might influence cancer development. Furthermore, the protective potential of docosahexaenoic acid in re-establishing the equilibrium between pro- and anti-inflammatory factors might represent a useful tool for preventive and therapeutic strategies.

Mitochondrial dysfunctions in Myalgic Encephalomyelitis / chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs) is classified by the World Health Organization as a disorder of the central nervous system. ME/cfs is an neuro-immune disorder accompanied by chronic low-grade inflammation, increased levels of oxidative and nitrosative stress (O&NS), O&NS-mediated damage to fatty acids, DNA and proteins, autoimmune reactions directed against neoantigens and brain disorders. Mitochondrial dysfunctions have been found in ME/cfs, e.g. lowered ATP production, impaired oxidative phosphorylation and mitochondrial damage. This paper reviews the pathways that may explain mitochondrial dysfunctions in ME/cfs. Increased levels of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-α, and elastase, and increased O&NS may inhibit mitochondrial respiration, decrease the activities of the electron transport chain and mitochondrial membrane potential, increase mitochondrial membrane permeability, interfere with ATP production and cause mitochondrial shutdown. The activated O&NS pathways may additionally lead to damage of mitochondrial DNA and membranes thus decreasing membrane fluidity. Lowered levels of antioxidants, zinc and coenzyme Q10, and ω3 polyunsaturated fatty acids in ME/cfs may further aggravate the activated immuno-inflammatory and O&NS pathways. Therefore, it may be concluded that immuno-inflammatory and O&NS pathways may play a role in the mitochondrial dysfunctions and consequently the bioenergetic abnormalities seen in patients with ME/cfs. Defects in ATP production and the electron transport complex, in turn, are associated with an elevated production of superoxide and hydrogen peroxide in mitochondria creating adaptive and synergistic damage. It is argued that mitochondrial dysfunctions, e.g. lowered ATP production, may play a role in the onset of ME/cfs symptoms, e.g. fatigue and post exertional malaise, and may explain in part the central metabolic abnormalities observed in ME/cfs, e.g. glucose hypometabolism and cerebral hypoperfusion.

Concurrent Physical Activity Modifies the Association between n3 Long-Chain Fatty Acids and Cardiometabolic Risk in Midlife Adults

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.