Polyunsaturated Fatty Acids In Fish Oil Research Articles

Cranberry juice decreases oxidative stress and improves glucose metabolism in patients with rheumatoid arthritis supplemented with fish oil

BackgroundBeneficial effects of fish oil n-3 polyunsaturated fatty acids (PUFAs) have been reported in rheumatoid arthritis (RA), however, high doses of n-3 fatty acids have been associated with increased total and LDL cholesterol and impaired glucose metabolism. Cranberry products have been reported to improve markers of oxidative stress, inflammation, and the metabolic profile in patients with type 2 diabetes mellitus and with metabolic syndrome. We hypothesized that including low-energy cranberry juice on a regimen of fish oil supplementation could improve oxidative stress and attenuate the undesirable effects of fish oil in lipid and glucose metabolism in patients with RA. MethodsA 90-days randomized controlled trial was conducted. Patients (n = 70) were assigned to one of three groups: control (C); fish oil (FO) received 3 g of fish oil PUFAs supplementation/day; and fish oil and cranberry (FOCR) received 3 g of fish oil PUFAs and 500 mL of cranberry juice/day. ResultsThere was no difference in parameters between FO and the C. FOCR group showed decreased glucose (p = 0.0225), lipid (p = 0.0079), protein (p = 0.0063) oxidation, and Oxidative Stress Index (p = 0.0375) values compared to FO. FOCR reduced glucose values (p = 0.0104), triacylglycerol (p = 0.0065), protein oxidation (p = 0.0042) and Oxidative Stress Index (OSI) (p = 0.0053) compared to the C. Compared to baseline, FO group decreased triacylglycerol (p = 0.0374) and increased glucose (p 0.0001), whereas FOCR group decreased triacylglycerol (p = 0.0398) values. Conclusion500 mL/day of reduced-calorie cranberry juice in patients with RA using fish oil supplementation decreased lipid, protein oxidation and OSI.

Dietary and nutritional value of fish and fish origin food products

Present review article explains the dietary and nutritional value of various fish derived natural food products. Dietary use of fish is a good source of important nutrients such as proteins, fats, vitamins and minerals.. Fish oil possesses polyunsaturated fatty acids (PUFAs) mainly omega-3 fatty acids, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and eicosanoids. Fish consumption is world's prime source of high-quality protein; and about 14–16 percent of the animal protein consumed worldwide. This article also emphasizes therapeutic uses of fish oil in healing of wounds, hyperpigmentation, dermatitis, and in cardiovascular risks. Fish oil usage is good for skin-related diseases and for photoageing, cancer, dermatitis, wound healing, and melanogenesis. Fish oil polyunsaturated fatty acids (PUFAs) are highly beneficial in cardiovascular problems and dermatitis. These also affect neurotransmitter signaling and second messengers and shows antidepressant activity. In the present review various local, national, and international processed fish derived food currently available in the market fish dishes have been mentioned.

Cosmetic and Therapeutic Applications of Fish Oil's Fatty Acids on the Skin.

Fish oil has been broadly reported as a potential supplement to ameliorate the severity of some skin disorders such as photoaging, skin cancer, allergy, dermatitis, cutaneous wounds, and melanogenesis. There has been increasing interest in the relationship of fish oil with skin protection and homeostasis, especially with respect to the omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). The other PUFAs, such as α-linolenic acid (ALA) and linoleic acid (LA), also show a beneficial effect on the skin. The major mechanisms of PUFAs for attenuating cutaneous inflammation are the competition with the inflammatory arachidonic acid and the inhibition of proinflammatory eicosanoid production. On the other hand, PUFAs in fish oil can be the regulators that affect the synthesis and activity of cytokines for promoting wound healing. A systemic review was conducted to demonstrate the association between fish oil supplementation and the benefits to the skin. The following describes the different cosmetic and therapeutic approaches using fatty acids derived from fish oil, especially ALA, LA, DHA, and EPA. This review summarizes the cutaneous application of fish oil and the related fatty acids in the cell-based, animal-based, and clinical models. The research data relating to fish oil treatment of skin disorders suggest a way forward for generating advances in cosmetic and dermatological uses.

Co-Enzyme Q10 and n-3 Polyunsaturated Fatty Acid Supplementation Reverse Intermittent Hypoxia-Induced Growth Restriction and Improved Antioxidant Profiles in Neonatal Rats.

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

Differential partitioning of rumen-protected n–3 and n–6 fatty acids into muscles with different metabolism

Bioavailability of polyunsaturated fatty acids (PUFA) in ruminants is enhanced by their protection from ruminal biohydrogenation. Both n–3 and n–6 PUFA fulfil important physiological functions. We investigated potentially different incorporation patterns of these functional PUFA into three beef muscles with different activity characteristics. We supplemented 33 Angus heifers with rumen-protected oils characterized either by mainly C18:2 n–6 (linoleic acid (LA) in sunflower oil) or by C20:5 (eicosapentaenoic acid (EPA)) and C22:6 (docosahexaenoic acid (DHA)), both prevalent n–3 PUFA in fish oil. Contents and proportions of n–3 and n–6 PUFA of total fatty acids were elevated in the muscles of the respective diet group but they were partitioned differently into the muscles. For EPA and DHA, but not for LA, the diet effect was more distinct in the extensor carpi radialis compared to longissimus thoracis and biceps femoris. Partitioning of PUFA in metabolism could be related to muscle function. This has to be confirmed in other muscles, adipose tissues and organs.

Role of GPR40 for Fish Oil PUFA-mediated BDNF Synthesis in the Monkey Hippocampus

Background: Polyunsaturated fatty acids (PUFA) are known to be crucial for learning and memory. However, the detailed mechanism of PUFA effects upon neuronal functions remains almost unknown except for the possible facilitation of membrane fluidity. G-protein coupled receptor 40 (GPR40) was found to induce Ca2+ mobilization in response to diverse PUFA. Thereafter, the authors found GPR40 expression in the newborn neurons of the monkey hippocampus after ischemia. This suggested implications of PUFA-mediated GPR40 signaling for adult neurogenesis underlying learning and memory. Objective: This study aims at evaluating whether PUFA-mediated GPR40 activation can affect synthesis of brain-derived neurotrophic factor (BDNF) with the aid of its proteolytic enzyme furin. Methods: Monkeys underwent 20 min transient whole brain ischemia by clamping both the innominate and left subclavian arteries. On days 7 and 15 after ischemia/reperfusion, when adult neurogenesis was shown to be maximal previously by the authors, the brain samples were resected. By the Western blotting analysis of mature-BDNF (m-BDNF), pro-BDNF and furin, syntheses of BDNF in response to two GPR40 agonists as well as selective GPR40 antagonist GW1100, were studied using normal and post-ischemic monkey dentate gyrus (DG) tissue extracts. Results: Both up-regulation of m-BDNF synthesis in response to two GPR40 agonists; fish oil PUFA and docosahexaenoic acid (DHA) and its down-regulation in response to GW1100, were observed. GPR40 antagonist inhibited m-BDNF synthesis, whereas two GPR40 agonists stimulated m-BDNF synthesis conceivably via furin activation. Cleavage of p-BDNF to m-BDNF by furin as well as syntheses of m-BDNF and furin in the DG tissues, occurred immediately after incubation with fish oil PUFA or DHA. Dynamic changes of GPR40, m-BDNF synthesis, and furin occurred simultaneously. Conclusions: These data, although correlative, suggested that m-BDNF may be synthesized by the cleavage of pre-stocked pro-BDNF and/or released from the cell store in response to PUFA. By activating GPR40 and furin, PUFA may be related to adult neurogenesis and the concomitant synaptic plasticity for learning and memory. To the best of our knowledge, this is the first report suggesting a role of GPR40 in PUFA-mediated m-BDNF synthesis.

Beneficial Effect of Fish Oil on Liver Steatosis: Involvement of Kupffer Cell polarization and Inflammasome Inactivation

Background Beneficial effect of marine derived fish oil on liver steatosis has been reported. Recently, a G protein-coupled receptor, FFA4 (aka GPR120) has been elucidated as an omega-3 fatty acid-sensing receptor. FFA4 expression in Kupffer cells and hepatocytes was reported. We investigated effect of polyunsaturated fatty acids on alcoholic fatty liver disease. As a mechanism study, we conducted experiments on inflammasome activation and Kupffer cell polarization. METHODS: Female C57/BL6 mouse were fed an ethanol or control-liquid diet with fish oil polyunsaturated fatty acids or saturated fatty acids for 2 weeks. Plasma transaminase, triglyceride levels, and liver histology were evaluated. Polarization of Kupffer cells and inflammasome activation were investigated by RT-PCR and Western analysis. RESULTS: First we confirmed FFA4 expression in Kupffer cells and hepatocytes. Liver steatosis induced by ethanol-liquid diet was deminished in mouse fed the ethanol plus fish oil diet but not corn oil diet. Fish oil supplementation also decreased plasma transaminase and triglyceride levels. Furthermore, ethanol drinking induced M1 polarization of Kupffer cells. However, fish oil administration polarized Kupffer cells into M2 phenotype. In addition mRNA expression of inflammasome components, such as NLRP3, ASC, and caspase-1 were decreased by fish oil supplementation, which led to reduced IL-1β production. SUMMARY: Supplementation of fish oil alleviated fat accumulation in a mouse model of alcoholic fatty liver disease. Fish oil inducing M2 polarization of Kupffer cells and inhibiting inflammasome activation were involved in anti-inflammatory and anti-steatosis effects of fish oil.

Comparison of Infrared Spectroscopy and Nuclear Magnetic Resonance Techniques in Tandem with Multivariable Selection for Rapid Determination of ω-3 Polyunsaturated Fatty Acids in Fish Oil

This study investigated the potential of using four spectroscopic techniques including visible–short-wave near infrared, long-wave near infrared (LNIR), mid-infrared, and nuclear magnetic resonance (NMR) spectroscopy in tandem with multivariable selection and calibration for rapid determination of three important ω-3 polyunsaturated fatty acids (PUFA), namely eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) in fish oil. Quantitative models were established between the spectral data and reference PUFA contents of samples based on partial least squares regression (PLSR) algorithm. Successive projections algorithm (SPA) and uninformative variable elimination (UVE) were used to select the most important variables for prediction. The average decrements of 23.20 % for root mean square error of cross-validation (RMSECV) and 64.90 % for the absolute value between root mean square error of calibration and RMSECV (AV_RMSE) in all 12 cases achieved after over 90 % variables were eliminated. UVE was also found to be helpful to improve the efficiency of SPA’s variable selection in 8/12 cases. The best predictions for EPA, DHA, and DPA were all achieved by NMR spectroscopy (determination coefficients of cross-validation (r CV 2 ) of 0.970, 0.982, and 0.983 and the RMSECV of 11.48, 4.73, and 0.77 mg/g for the EPA, DHA, and DPA predictions, respectively). LNIR spectra also did good predictions similar to NMR. The results demonstrated that the laborious and time-consuming gas chromatography method could be replaced by spectroscopic techniques in tandem with PLSR modeling and variable selection in order to provide a rapid and reliable inspection of PUFA in fish oil.

Connecting Model Membrane Experiments to In Vivo Studies: DHA Acyl Chains Incorporate into Raft-Like Membranes more than EPA in Model Membranes, In Vitro, and In Vivo

N-3 polyunsaturated fatty acids (PUFA) enriched in fish oil are increasingly recognized to have potential benefits for treatment of inflammatory and metabolic disorders; however, their mode of action remains unclear. One emerging hypothesis is n-3 PUFA acyl chains disrupt the molecular organization of lipid raft domains. In the present study, we first compared the effects of the two major n-3 PUFAs of fish oil, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, on molecular organization in model membranes.

Pericardial delivery of omega-3 fatty acid: a novel approach to reducing myocardial infarct sizes and arrhythmias

Basic and clinical evidence suggests that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) decrease fatal arrhythmias and infarct sizes. This study investigated if pericardial delivery of n-3 PUFAs would protect the myocardium from ischemic damages and arrhythmias. Acute myocardial infarctions were induced in 23 pigs with either 45 min balloon inflations or clamp occlusions of the left anterior descending coronary arteries and 180 min reperfusion. Docosahexaenoic acid (C22:6n-3, DHA, 45 mg), one of the main n-3 PUFAs in fish oil, was infused within the pericardial space only during the 40-min stabilizing phase, 45 min ischemia and initial 5 min reperfusion. Hemodynamics and cardiac functions were very similar between the DHA-treated and control groups. However, DHA therapy significantly reduced infarct sizes from 56.8 +/- 4.9% for controls (n = 12) to 28.8 +/- 7.9% (P < 0.01) for DHA-treated animals (n = 11). Compared with controls, DHA-treated animals significantly decreased heart rates and reduced ventricular arrhythmia scores during ischemia. Furthermore, three (25%) control animals experienced eight episodes of ventricular fibrillation (VF), and two died subsequent to unsuccessful defibrillation. In contrast, only 1 (9%) of 11 DHA-treated pigs elicited one episode of VF that was successfully converted via defibrillation to normal rhythm; thus, mortality was reduced from 17% in the controls to 0% in the DHA-treated animals. These data demonstrate that pericardial infusion of n-3 PUFA DHA can significantly reduce both malignant arrhythmias and infarct sizes in a porcine infarct model. Pericardial administration of n-3 PUFAs could represent a novel approach to treating or preventing myocardial infarctions.

Cardiovascular diseases and red meat

Cardiovascular diseases and red meat

Polyunsaturated Fatty Acids in Male and Female Reproduction1

In Westernized societies, average consumption of n-6 polyunsaturated fatty acids (PUFAs) far exceeds nutritional requirements. The ratio of n-6 to n-3 PUFAs is generally >10:1 whereas on a primitive human diet it was closer to 1:1. Diets fed to intensively farmed livestock have followed a similar trend. Both n-6 and n-3 PUFAs can influence reproductive processes through a variety of mechanisms. They provide the precursors for prostaglandin synthesis and can modulate the expression patterns of many key enzymes involved in both prostaglandin and steroid metabolism. They are essential components of all cell membranes. The proportions of different PUFAs in tissues of the reproductive tract reflect dietary consumption. PUFA supplements (particularly n-3 PUFAs in fish oil) are promoted for general health reasons. Fish oils may also benefit fertility in cattle and reduce the risk of preterm labor in women, but in both cases current evidence to support this is inconclusive. Gamma-linolenic acid containing oils can alter the types of prostaglandins produced by cells in vitro, but published data to support claims relating to effects on reproductive health are lacking. Spermatozoa require a high PUFA content to provide the plasma membrane with the fluidity essential at fertilization. However, this makes spermatozoa particularly vulnerable to attack by reactive oxygen species, and lifestyle factors promoting oxidative stress have clear associations with reduced fertility. Adequately powered trials that control for the ratios of different PUFAs consumed are required to determine the extent to which this aspect of our diets does influence our fertility.

Induction of Cd36 expression elicited by fish oil PUFA in spontaneously hypertensive rats

Cd36 is an integral membrane glycoprotein expressed on the surface of cells active in fatty acid metabolism (adipocytes, muscle cells, platelets, monocytes, heart and intestine cells). This protein plays diverse functions including uptake of long-chain fatty acids and oxidized low-density lipoproteins. A recent report demonstrates that Cd36 deficiency underlies insulin resistance, defective fatty acid metabolism and hypertriglyceridemia in spontaneously hypertensive rats (SHRs). Cd36 is a tightly regulated protein whose expression is modulated through peroxisome proliferator-activated receptor (PPAR) transcription factors, by conditions that alter lipid metabolism such as diabetes mellitus and high-fat feeding. The purpose of this study was to evaluate the effect of dietary fish oil, rich in n-3 polyunsaturated fatty acids (PUFAs), on metabolic parameters and on the expression levels of Cd36 in adipose tissue in the SHR. Spontaneously hypertensive rats showed lower Cd36 mRNA levels when compared to Kyoto-Wistar (KW) rats (control). After 6 weeks of fish oil (FO) administration, this group of SHRs (FO-SHR) presented increased levels of Cd36 mRNA, concomitantly with decreased insulin, free fatty acids (FFAs), triglycerides, cholesterol, LDL, HDL, total lipids and blood pressure, in comparison to control rats that received a corn–canola oil diet. The study confirmed the beneficial effects of fish oil administration on the metabolic syndrome, suggesting that the induction of Cd36 expression could be one of the molecular mechanisms elicited by fish oil PUFAs.

Inhibition by eicosapentaenoic acid of IL-1β-induced PGHS-2 expression in human microvascular endothelial cells: involvement of lipoxygenase-derived metabolites and p38 MAPK pathway

Prostaglandin H synthase 2 (PGHS-2), a highly inducible isoenzyme, is responsible for overproduction of the prostaglandins (PGs) in inflammatory sites. We established that among fish oil polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), but not docosahexaenoic acid (DHA), greatly decreased interleukin-1β (IL-1β)-induced PGHS-2 expression in human pulmonary microvascular endothelial cells (HPMECs). Lipoxygenase products 12 ( S)-hydroperoxyeicosapentaenoic acid (( S)-HpEPE), 15 ( S)-HpEPE and leukotriene (LT) D5 reproduced similar inhibitory effect, suggesting that they may be the intermediate metabolites responsible for PGHS-2 down-regulation by EPA. Accordingly, the EPA effect is prevented by nordihydroguaiaretic acid (NDGA) and by REV 5901, nonspecific and specific 5-lipoxygenase inhibitors, respectively. Besides, inhibition of cyclooxygenase activity by ibuprofen, indomethacin or aspirin was not able to prevent this effect. Moreover, cyclooxygenase metabolites of EPA (PGs D3, E3 and I3) markedly potentiate IL-1β-induced PGHS-2 expression, probably by increasing intracellular cAMP levels. Peroxisome proliferator-activated receptors (PPARs) are known to be activated by fatty acids (FAs) such as EPA. We found here that HPMECs express only weak amounts of PPARα and PPARγ whose activation by synthetic agonists, Wy-14,643 and ciglitazone, does not cause any inhibition of IL-1β-induced PGHS-2 expression. This finding ruled out the involvement of PPARs in the EPA inhibitory effect. In addition, we established that EPA, which failed to inhibit nuclear factor-κB (NF-κB) activation, suppressed p38 mitogen-activated protein kinase (MAPK) phosphorylation in stimulated HPMECs. Our data demonstrate that EPA, unlike DHA, down-regulates PGHS-2 expression in HPMECs probably through its 5-lipoxygenase-dependent metabolites and advocates a beneficial role for this FA in limiting inflammatory response.

Dietary modification of inflammation with lipids.

The n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in high proportions in oily fish and fish oils. The n-3 PUFA are structurally and functionally distinct from the n-6 PUFA. Typically, human inflammatory cells contain high proportions of the n-6 PUFA arachidonic acid and low proportions of n-3 PUFA. The significance of this difference is that arachidonic acid is the precursor of 2-series prostaglandins and 4-series leukotrienes, which are highly-active mediators of inflammation. Feeding fish oil results in partial replacement of arachidonic acid in inflammatory cell membranes by EPA. This change leads to decreased production of arachidonic acid-derived mediators. This response alone is a potentially beneficial anti-inflammatory effect of n-3 PUFA. However, n-3 PUFA have a number of other effects which might occur downstream of altered eicosanoid production or might be independent of this activity. For example, animal and human studies have shown that dietary fish oil results in suppressed production of pro-inflammatory cytokines and can decrease adhesion molecule expression. These effects occur at the level of altered gene expression. This action might come about through antagonism of the effects of arachidonic acid-derived mediators or through more direct actions on the intracellular signalling pathways which lead to activation of transcription factors such as nuclear factor kappa B (NFB). Recent studies have shown that n-3 PUFA can down regulate the activity of the nuclear transcription factor NFB. Fish oil feeding has been shown to ameliorate the symptoms in some animal models of chronic inflammatory disease and to protect against the effects of endotoxin and similar inflammatory challenges. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some patients with asthma, supporting the idea that the n-3 PUFA in fish oil are anti-inflammatory. There are indications that inclusion of n-3 PUFA in enteral and parenteral formulas might be beneficial to patients in intensive care or post-surgery.

Polyunsaturated fatty acids, inflammation, and immunity.

The fatty acid composition of inflammatory and immune cells is sensitive to change according to the fatty acid composition of the diet. In particular, the proportion of different types of polyunsaturated fatty acids (PUFA) in these cells is readily changed, and this provides a link between dietary PUFA intake, inflammation, and immunity. The n-6 PUFA arachidonic acid (AA) is the precursor of prostaglandins, leukotrienes, and related compounds, which have important roles in inflammation and in the regulation of immunity. Fish oil contains the n-3 PUFA eicosapentaenoic acid (EPA). Feeding fish oil results in partial replacement of AA in cell membranes by EPA. This leads to decreased production of AA-derived mediators. In addition, EPA is a substrate for cyclooxygenase and lipoxygenase and gives rise to mediators that often have different biological actions or potencies than those formed from AA. Animal studies have shown that dietary fish oil results in altered lymphocyte function and in suppressed production of proinflammatory cytokines by macrophages. Supplementation of the diet of healthy human volunteers with fish oil-derived n-3 PUFA results in decreased monocyte and neutrophil chemotaxis and decreased production of proinflammatory cytokines. Fish oil feeding has been shown to ameliorate the symptoms of some animal models of autoimmune disease. Clinical studies have reported that fish oil supplementation has beneficial effects in rheumatoid arthritis, inflammatory bowel disease, and among some asthmatics, supporting the idea that the n-3 PUFA in fish oil are anti-inflammatory and immunomodulatory.

Biohydrogenation and digestion of long chain fatty acids in steers fed on different sources of lipid

Rumen biohydrogenation of dietary polyunsaturated fatty acids (PUFA) is a significant limitation on any attempt to manipulate the PUFA content of ruminant products (meat or milk). This study examined rumen biohydrogenation of PUFA, the effects of PUFA on other aspects of rumen metabolism and fatty acid flow to and digestion in the small intestine of steers fed on different sources of lipid. Animals were fed ad libitum on grass silage and one of four concentrates (60:40 forage:concentrate on a dry matter basis) containing differing sources of lipid: megalac (rich in C16:0; M), linseed (rich in C18:3n-3; L), fish oil (rich in C20:5n-3 and C22:6n-3; FO) and a mixture of linseed/fish oil (LFO). Diets were formulated so that total dietary oil intake was approximately 60 g/kg of the DM intake, approximately half of which was from the experimental test oil. Rumen NH3-N (P = 0·09) and total VFA concentrations (P = 0·007) were higher on L, FO and LFO compared to M. Dry matter intakes did not differ across treatments and averaged 7·2 kg/day. Intake and flow of fatty acids to the duodenum was 323, 438, 344 and 381 (S.E.M. 9·1; P &lt; 0·001) and 432, 489, 412 and 465 (S.E.M. 18·5; P &lt; 0·1) g/day for M, L, FO and LFO, respectively. Biohydrogenation of C18:1n-9 was lower than all the other unsaturated fatty acids and it was lower of FO and LFO compared to M and L, on average 66·1 and 72·2 %, respectively. Biohydrogenation of C18:2n-6 averaged 89·8 % across treatments and was lower (P &lt; 0·05) on M compared to L and FO. Biohydrogenation of C18:3n-3 averaged 92·1 % across treatments and was lowest on M (88·8 %) and highest on L and LFO (94·3 %). Biohydrogenation of C20:5n-3 and C22:6n-3 averaged approximately 91 and 89 % across the treatments, respectively. Small intestinal digestibilities of all fatty acids were high. In conclusion, feeding different sources of lipid with different fatty acid composition had significant effects on rumen function. The PUFA in whole linseed were only partially protected from biohydrogenation by the seed coat and in contrast to previous reports the C20 PUFA in fish oil were biohydrogenated to a large extent.

Effect of tetracosahexaenoic acid on the content and release of histamine, and eicosanoid production in MC/9 mouse mast cell.

6,9,12,15,18,21-Tetracosahexaenoic acid (24:6n-3) was isolated from a brittle star, Ophiura sarsi Lütken, at >95% purity to evaluate its physiological functions. The effects of 24:6n-3 on the production of leukotriene (LT)-related compounds such as LTB4, LTC4 and 5-hydroxyeicosatetraenoic acid, and the accumulation and release of histamine in an MC/9 mouse mast cell line were studied. We found that 24:6n-3 could inhibit the antigen-stimulated production of LT-related compounds as well as other n-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3), which are major n-3 PUFA in fish oils; 24:6n-3 was also shown to reduce the histamine content in MC/9 cells at 25 microM (27% reduction from the control), and the effect was diminished with increase of the fatty acid concentration (up to 100 microM). These two n-3 PUFA, 20:5n-3 and 22:6n-3, also reduced the histamine content (16 and 20% reduction at 25 microM, respectively), whereas arachidonic acid (20:4n-6) increased it (18% increase at 25 microM). Spontaneous- and antigen-induced release of histamine was not influenced with these PUFA (at 25 microM). Ionophore-stimulated release of histamine was suppressed by the PUFA (13, 9, 15, and 11% reduction with 20:4n-6, 20:5n-3, 22:6n-3, and 24:6n-3, respectively). The patterns of the effects of 24:6n-3 on the synthesis of eicosanoids and histamine content were more similar to those of 22:6n-3 than 20:5n-3. From these results, 24:6n-3 can be expected to have anti-inflammatory activity and antiallergic activities similar to those of 22:6n-3.

Mitochondrion is the principal target for nutritional and pharmacological control of triglyceride metabolism

Fish oil polyunsaturated fatty acids and fibrate hypolipidemic drugs are potent hypotriglyceridemic agents that act by increasing fatty acid catabolism and decreasing triglyceride synthesis and secretion by the liver. A major unresolved issue is whether this hypotriglyceridemic effect can occur independent of induction of peroxisomal beta-oxidation, a predisposing factor for hepatocarcinogenesis. The present study was undertaken to determine which component of fish oil, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), is responsible for its triglyceride-lowering effect. We demonstrate that EPA and not DHA is the hypotriglyceridemic component of fish oil and that mitochondria and not peroxisomes are the principal target. Results obtained by fenofibrate feeding support the hypothesis that the mitochondrion is the primary site for the hypotriglyceridemic effect. In contrast to fibrates, EPA did not affect hepatic apolipoprotein C-III gene expression. Therefore, increased mitochondrial beta-oxidation with a concomitant decrease in triglyceride synthesis and secretion seems to be the primary mechanism underlying the hypotriglyceridemic effect of EPA and fibrates in rats, rabbits and possibly also in humans. In addition, these data show that lowering of plasma triglycerides can occur independently of any deleterious peroxisome proliferation.

Does vegetable oil attenuate the beneficial effects of fish oil in reducing risk factors for cardiovascular disease?

Contradictory reports on the protective effect of fish consumption on cardiovascular disease (CVD) risk could be due to variations in the intake of n-3 and n-6 polyunsaturated fatty acids (PUFAs). Metabolic competition between n-3 and n-6 PUFAs suggests that n-6 PUFAs in vegetable oils could attenuate the efficacy of n-3 PUFAs in fish oil to favorably alter endpoints relevant to CVD risk. We determined the effects of varying dietary amounts of fish oil on lipid and thrombotic endpoints relevant to risk factors for CVD and whether these effects were attenuated by vegetable oils. Two randomized, double-blind, placebo-controlled, parallel studies were conducted in human subjects fed varying amounts of n-3 and n-6 PUFAs; n-3 PUFA intake was varied by using fish or placebo oil capsules, and n-6 PUFA intake was modified by incorporating varying amounts of safflower oil into the diet. Endpoints included changes in membrane fatty acid composition, blood lipids, and thrombotic profile. The results indicated that absolute amounts of fish oil, and not the relative amounts of fish and vegetable oil (ratios of n-3 to n-6 PUFAs), determined the magnitude of the reduction of arachidonic acid and increase in eicosapentaenoic acid in phospholipids of plasma and platelets. The suppression of plasma triacylglycerols by fish oil was not affected by varying amounts of dietary n-6 PUFAs. Fibrinogen concentrations decreased with 15 g but not with 9 g fish oil/d fed at the same ratio of n-3 to n-6 PUFAs. The efficacy of fish oil in favorably modifying certain risk factors for CVD was not attenuated by vegetable oil.