Dietary n-3 (omega-3) polyunsaturated fatty acid effects on animal tumorigenesis.

Environmental variables influence the incidence and expression of disease. Dietary fat is one environmental variable that has been associated experimentally and epidemiologically with alterations in certain types of tumorigenesis. Recently, detailed biochemical analyses have shown that not all fatty acid families possess the same tumor-promoting potential. In general, diets containing high levels of the n-6 polyunsaturated fatty acids have routinely enhanced tumorigenesis in lipid sensitive carcinogen-induced and tumor transplant tumor models, whereas diets with equivalent levels of n-3 polyunsaturated fatty acids have diminished tumorigenesis. At present, there is no definitive biochemical mechanism that fully explains these observations, but several possibilities have been proposed. One of the most attractive of these hypotheses is that each polyunsaturated fatty acid family has an individual effect on eicosanoid metabolism which determines its tumor-promoting potential. Regardless of current uncertainties about mechanisms of action, however, results of numerous animal models affirm the importance of qualitative, as well as quantitative, dietary lipid differences on tumorigenesis. This knowledge strengthens the probability that further advances in our understanding of lipid-tumor interrelationships will have important preventive and therapeutic medical benefits.     

Identification of novel autoxidation products of the omega-3 fatty acid eicosapentaenoic acid in vitro and in vivo

Increased intake of fish oil rich in the omega-3 fatty acids eicosapentaenoic acid (EPA, C20:5 omega-3) and docosahexaenoic acid (DHA, C22:6 omega-3) reduces the incidence of human disorders such as atherosclerotic cardiovascular disease. However, mechanisms that contribute to the beneficial effects of fish oil consumption are poorly understood. Mounting evidence suggests that oxidation products of EPA and DHA may be responsible, at least in part, for these benefits. Previously, we have defined the free radical-induced oxidation of arachidonic acid in vitro and in vivo and have proposed a unified mechanism for its peroxidation. We hypothesize that the oxidation of EPA can be rationally defined but would be predicted to be significantly more complex than arachidonate because of the fact that EPA contains an addition carbon-carbon double bond. Herein, we present, for the first time, a unified mechanism for the peroxidation of EPA. Novel oxidation products were identified employing state-of-the-art mass spectrometric techniques including Ag(+) coordination ionspray and atmospheric pressure chemical ionization mass spectrometry. Predicted compounds detected both in vitro and in vivo included monocylic peroxides, serial cyclic peroxides, bicyclic endoperoxides, and dioxolane-endoperoxides. Systematic study of the peroxidation of EPA provides the basis to examine the role of specific oxidation products as mediators of the biological effects of fish oil.     

Substrate specificity, regioselectivity and cryptoregiochemistry of plant and animal omega-3 fatty acid desaturases

In order to define the substrate requirements, regiochemistry and cryptoregiochemistry of the omega-3 fatty acid desaturases involved in polyunsaturated fatty acid formation, the genes Fad3 and fat-1 from Brassica napus and the nematode Caenorhabditis elegans respectively were expressed in baker's yeast (Saccharomyces cerevisiae). Various fatty acids, including deuterium-labelled thia-fatty acids, were supplied to growing cultures of transformed yeast. The results from GC-MS analysis of the desaturated products indicate that both the plant and animal desaturases act on unsaturated substrates of 16-20 carbons with a preference for omega-6-unsaturated fatty acids. The regioselectivities of both enzymes were confirmed to be that of omega-3 desaturases. The primary deuterium kinetic isotope effects at C-15 and C-16 of a C(18) fatty acid analogue were measured via competitive incubation experiments. Whereas k(H)/k(D) at the omega-3 position was shown to be large, essentially no kinetic isotope effect at the omega-2 position was observed for the plant or the nematode enzymes. These results indicate that omega-3 desaturation is initiated by an energetically difficult C-H bond cleavage at the carbon closer to the carboxyl terminus. These results will be discussed in the context of a general model relating the structure and function of membrane-bound fatty acid desaturases featuring different regioselectivities.     

Effect of omega-3 fatty acids on the modification of erythrocyte membrane fatty acid content including oleic acid in peritoneal dialysis patients

Erythrocyte membrane fatty acids (FA), such as oleic acid, are related to acute coronary syndrome. There is no report about the effect of omega-3 FA on oleic acid in peritoneal dialysis (PD) patients. We hypothesized that omega-3 FA can modify erythrocyte membrane FA, including oleic acid, in PD patients. In a double-blind, randomized, placebo-controlled study, 18 patients who were treated with PD for at least 6 months were randomized to treatment for 12 weeks with omega-3 FA or placebo. Erythrocyte membrane FA content was measured by gas chromatography at baseline and after 12 weeks. The erythrocyte membrane content of eicosapentaenoic acid and docosahexaenoic acid was significantly increased and saturated FA and oleic acid were significantly decreased in the omega-3 FA supplementation group after 12 weeks compared to baseline. In conclusion, erythrocyte membrane FA content, including oleic acid, was significantly modified by omega-3 FA supplementation for 12 weeks in PD patients.     

Metabolism and functional effects of plant-derived omega-3 fatty acids in humans

Alpha-linolenic acid (ALA) is an essential fatty acid and the substrate for the synthesis of longer-chain, more unsaturated ω-3 fatty acids, eicosapentaenoic acid (EPA), docosapentaenoic acid and docosahexaenoic acid (DHA). EPA and DHA are associated with human health benefits. The primary source of EPA and DHA is seafood. There is a need for sustainable sources of biologically active ω-3 fatty acids. Certain plants contain high concentrations of ALA and stearidonic acid (SDA). Here we review the literature on the metabolism of ALA and SDA in humans, the impact of increased ALA and SDA consumption on concentrations of EPA and DHA in blood and cell lipid pools, and the extent to which ALA and SDA might have health benefits. Although it is generally considered that humans have limited capacity for conversion of ALA to EPA and DHA, sex differences in conversion to DHA have been identified. If conversion of ALA to EPA and DHA is limited, then ALA may have a smaller health benefit than EPA and DHA. SDA is more readily converted to EPA and appears to offer better potential for health improvement than ALA. However, conversion of both ALA and SDA to DHA is limited in most humans.     

Tolerability of omega-3 fatty acid supplements in perinatal women

BACKGROUND: Benefits of omega-3 fatty acids in perinatal women are well documented, although fish intake has declined among perinatal women. OBJECTIVE: To determine the tolerability of omega-3 fatty acid supplementation in perinatal women. DESIGN: Pregnant and postpartum women with major depressive disorder (MDD) entered an 8-week double-blind, placebo-controlled trial of omega-3 fatty acids. Four capsules provided 1.84 g/day of eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA), or matching placebo (corn oil with 1% fish oil to maintain blind). Tolerability was assessed by clinician interview biweekly. RESULTS: Fifty-nine women enrolled. Thirteen (22%) reported mainly transient side effects including dizziness, diarrhea, nausea, burping, heartburn/reflux, difficulty swallowing capsules, unpleasant breath/bad taste or feeling tired. The most common were unpleasant breath/bad taste and heartburn/reflux. Six reporting side effects received omega-3 fatty acids; seven received placebo. Neither pregnant nor postpartum women discontinued due to intolerability. CONCLUSIONS: Omega-3 fatty acid supplements were well tolerated by perinatal women.     

Effect of a conjugated linoleic acid and omega-3 fatty acid mixture on body composition and adiponectin

This study aimed to determine the effect of supplementation with conjugated linoleic acids (CLAs) plus n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) on body composition, adiposity, and hormone levels in young and older, lean and obese men. Young (31.4+/-3.9 years) lean (BMI, 23.6+/-1.5 kg/m2; n=13) and obese (BMI, 32.4+/-1.9 kg/m2; n=12) and older (56.5+/-4.6 years) lean (BMI, 23.6+/-1.5 kg/m2; n=20) and obese (BMI, 32.0+/-1.6 kg/m2; n=14) men participated in a double-blind placebo-controlled, randomized crossover study. Subjects received either 6 g/day control fat or 3 g/day CLA (50:50 cis-9, trans-11:trans-10, cis-12) and 3 g/day n-3 LC-PUFA for 12 weeks with a 12-week wash-out period between crossovers. Body composition was assessed by dual-energy X-ray absorptiometry. Fasting adiponectin, leptin, glucose, and insulin concentrations were measured and insulin resistance estimated by homeostasis model assessment for insulin resistance (HOMA-IR). In the younger obese subjects, CLA plus n-3 LC-PUFA supplementation compared with control fat did not result in increased abdominal fat and raised both fat-free mass (2.4%) and adiponectin levels (12%). CLA plus n-3 LC-PUFA showed no significant effects on HOMA-IR in any group but did increase fasting glucose in older obese subjects. In summary, supplementation with CLA plus n-3 LC-PUFA prevents increased abdominal fat mass and raises fat-free mass and adiponectin levels in younger obese individuals without deleteriously affecting insulin sensitivity, whereas these parameters in young and older lean and older obese individuals were unaffected, apart from increased fasting glucose in older obese men.     

Effects of diets enriched in omega-3 and omega-6 polyunsaturated fatty acids on offspring sex-ratio and maternal behavior in mice

There have been many trials describing the effects of polyunsaturated fatty acids (PUFA) on fecundity, neonatal development, and maternal behavior in humans, but few controlled studies in rodents. We examined the effects of a maternal diet high in omega 3 (N-3) or omega 6 (N-6) PUFA on NIH Swiss mice. Female mice were ad libitum fed one of three complete and balanced diets (N-3, enriched in menhaden oil; N-6, enriched in corn oil; C, control diet, Purina 5015) from age 4 wk until the end of the study. Mice were bred at approximately 19 wk and 27 wk of age, providing a total of 838 pups from 129 litters in two experiments. After weaning their pups from parity 1, behavior of dams was assessed on elevated-plus and open-field mazes. Although the fraction of male pups from the N-3 and C groups was not different from 0.5, dams on the N-6 diet birthed more daughters than sons (213 vs. 133; P < 0.001). Although maternal stress has been reported to favor birth of daughters, the behavior of N-6 dams was not different from controls. By contrast, the N-3 dams displayed greater anxiety, spending less time in the open arms and more time in the closed arms of the elevated maze and traveling less distance and exhibiting less exploratory behavior in the open field (P < 0.05). N-3 dams tended to produce smaller litters than C dams, and N-3-suckled pups gained less weight (P < 0.05). In conclusion, the N-3 diet had negative effects on murine fecundity and maternal behavior, whereas the N-6 diet favored birth of daughters.     

In vitro mimicry of essential fatty acid deficiency in human endothelial cells by TNFalpha impact of omega-3 versus omega-6 fatty acids

Severe endothelial abnormalities are a prominent feature in sepsis with cytokines such as tumor necrosis factor (TNF)alpha being implicated in the pathogenesis. As mimic to inflammation, human umbilical vascular endothelial cells (HUVEC) were incubated with TNFalpha for 22 h, in the absence or presence of the omega-6 fatty acid (FA), arachidonic acid (AA), or the alternative omega-3 FA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). TNFalpha caused marked alterations in the PUFA profile and long chain PUFA content of total phospholipids (PL) decreased. In contrast, there was a compensatory increase in mead acid [MA, 20:3(omega-9)], the hallmark acid of the essential fatty acid deficiency (EFAD) syndrome. Corresponding changes were noted in phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol, but not in the sphingomyelin fraction. Supplementation with AA, EPA, or DHA markedly increased the respective FA contents in the PL pools, suppressed the increase in MA, and resulted in a shift either toward further predominance of omega-6 or predominance of omega-3 FA. We conclude that short-term TNFalpha incubation of HUVEC causes an EFAD state hitherto only described for long-term malnutrition, and that endothelial cells are susceptible to differential influence by omega-3 versus omega-6 FA supplementation under these conditions.     

Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools

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

Cloning of higher plant omega-3 fatty acid desaturases.

Arabidopsis thaliana T-DNA transformants were screened for mutations affecting seed fatty acid composition. A mutant line was found with reduced levels of linolenic acid (18:3) due to a T-DNA insertion. Genomic DNA flanking the T-DNA insertion was used to obtain an Arabidopsis cDNA that encodes a polypeptide identified as a microsomal omega-3 fatty acid desaturase by its complementation of the mutation. Analysis of lipid content in transgenic tissues demonstrated that this enzyme is limiting for 18:3 production in Arabidopsis seeds and carrot hairy roots. This cDNA was used to isolate a related Arabidopsis cDNA, whose mRNA is accumulated to a much higher level in leaf tissue relative to root tissue. This related cDNA encodes a protein that is a homolog of the microsomal desaturase but has an N-terminal extension deduced to be a transit peptide, and its gene maps to a position consistent with that of the Arabidopsis fad D locus, which controls plastid omega-3 desaturation. These Arabidopsis cDNAs were used as hybridization probes to isolate cDNAs encoding homologous proteins from developing seeds of soybean and rapeseed. The high degree of sequence similarity between these sequences suggests that the omega-3 desaturases use a common enzyme mechanism.     

Effect of saturated, omega-3 and omega-6 polyunsaturated fatty acids on myocardial infarction

Dietary fatty acids have cholesterol lowering, antiatherogenic, and antiarrhythmic properties that decrease the risk of myocardial infarction (MI). This study was designed to study the effects of various oils rich in either polyunsaturated (omega-3 or omega-6) fatty acids (PUFA) or saturated fatty acids (SFA) on the severity of experimentally induced MI. Male albino Sprague-Dawley rats (100-150 g; n = 20) were fed diets enriched with fish oil (omega-3 PUFA), peanut oil (omega-6 PUFA), or coconut oil (SFA) for 60 days. Experimental MI was induced with isoproterenol. Mortality rates; serum enzymes aspartate amino transferase; alanine amino transferase; creatine phosphokinase (CPK); lipid profiles in serum, myocardium, and aorta; peroxide levels in heart and aorta; activities of catalase and superoxide dismutase; and levels of glutathione were measured. The results demonstrated that mortality rate, CPK levels, myocardial lipid peroxides, and glutathione levels were decreased in the omega-3 PUFA treated group. Maximum increase in parameters indicative of myocardial damage was seen in the coconut oil group. These findings suggest that dietary omega-3 PUFA offers maximum protection in experimentally induced MI in comparison to omega-6 PUFA and SFA enriched diets. SFA was found to have the least protective effect.     

Genetic adaptation of fatty-acid metabolism: a human-specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acids

Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LC-PUFAs) are essential for the development and function of the human brain. They can be obtained directly from food, e.g., fish, or synthesized from precursor molecules found in vegetable oils. To determine the importance of genetic variability to fatty-acid biosynthesis, we studied FADS1 and FADS2, which encode rate-limiting enzymes for fatty-acid conversion. We performed genome-wide genotyping (n = 5,652 individuals) and targeted resequencing (n = 960 individuals) of the FADS region in five European population cohorts. We also analyzed available genomic data from human populations, archaic hominins, and more distant primates. Our results show that present-day humans have two common FADS haplotypes-defined by 28 closely linked SNPs across 38.9 kb-that differ dramatically in their ability to generate LC-PUFAs. No independent effects on FADS activity were seen for rare SNPs detected by targeted resequencing. The more efficient, evolutionarily derived haplotype appeared after the lineage split leading to modern humans and Neanderthals and shows evidence of positive selection. This human-specific haplotype increases the efficiency of synthesizing essential long-chain fatty acids from precursors and thereby might have provided an advantage in environments with limited access to dietary LC-PUFAs. In the modern world, this haplotype has been associated with lifestyle-related diseases, such as coronary artery disease.     

Effects of omega-3 fatty acid on platelet serotonin responsivity in patients with schizophrenia

Studies suggest that the omega-3 fatty acid supplementation may be beneficial in reducing symptom severity in schizophrenia. The mechanism(s) underlying the clinical effect is not known. Serotonin (5-HT) has been implicated in the pathophysiology of schizophrenia and in the mechanism of some antipsychotic agents. 5-HT receptors are known to be modified by omega-3 fatty acids. We examined whether supplementation with the omega-3 fatty acid eicosapentaenoic acid (EPA)-modified 5-HT amplified ADP-induced platelet aggregation in patients with schizophrenia. Two grams of ethyl-EPA was administered daily for 6 months supplementally to ongoing antipsychotic treatment in 12 patients with chronic schizophrenia, using an open-label design. Red blood cell membrane fatty acids and platelet functions (platelet aggregation and dense granule secretion) were monitored at baseline, 1-, 3- and 6-months. The EPA levels were elevated more than five-fold in RBC membranes of all patients after 3 months supplementation, indicating a high degree of compliance. Consistent with previous reports, there was inhibition of ADP-induced platelet aggregation by EPA supplementation. Moreover, EPA markedly enhanced the 5-HT responsivity as measured by the magnitude of 5-HT amplification on ADP-induced platelet aggregation. Previously, we have demonstrated a significant inverse correlation between 5-HT responsivity and psychosis severity in unmedicated patients with schizophrenia. Taken together, the present data support the notion that EPA may be mediating its therapeutic effects in schizophrenia via modulation of the 5-HT2 receptor complex.     

A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans

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.     

Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose n3-HUFA in healthy volunteers

A subject's baseline FA composition may influence the ability of dietary highly unsaturated omega-3 FAs (n3-HUFA) to change circulating profiles of esterified FAs and their oxygenated metabolites. This study evaluates the influence of basal n3-HUFA and n3-oxylipin status on the magnitude of response to n3-HUFA consumption. Blood was collected from fasting subjects (n = 30) before and after treatment (4 weeks; 11 ± 2 mg/kg/day n3-HUFA ethyl esters). Esterified FAs were quantified in erythrocytes, platelets, and plasma by GC-MS. Esterified oxylipins were quantified in plasma by LC-MS/MS. Treatment with n3-HUFAs increased n3-HUFAs and decreased n6-HUFAs in all reservoirs and increased plasma n3-oxylipins without significantly changing n6-oxylipin concentrations. As subject basal n3-HUFAs increased, treatment-associated changes decreased, and this behavior was reflected in the percentage of 20:5n3 + 22:6n3 in red blood cell membrane FAs (i.e., the omega-3 index). To maintain an omega-3 index of 8% and thus reduce cardiovascular disease risk, our analyses suggest a maintenance dose of 7 mg/kg/day n3-HUFA ethyl esters for a 70-kg individual. These results suggest that the basal n3 index may have clinical utility to establish efficacious therapeutic experimental feeding regimens and to evaluate the USDA Dietary Guidelines recommendations for n3-HUFA consumption.     

The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases

Several sources of information suggest that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1-16.7/1. Western diets are deficient in omega-3 fatty acids, and have excessive amounts of omega-6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today's Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a lower omega-6/omega-3 ratio), exert suppressive effects. In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/omega-3 ratio in women with breast cancer was associated with decreased risk. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition. A lower ratio of omega-6/omega-3 fatty acids is more desirable in reducing the risk of many of the chronic diseases of high prevalence in Western societies, as well as in the developing countries.     

Effect of omega-3 fatty acids on haemostatic functions in urocortin-treated obese rats

Urocortin 1 (UCN1) decreases food intake. We investigated the effects of UCN1 and omega-3 fatty acids (FA) on metabolic and coagulation parameters in high fat diet (HFD)-fed rats. Fifty male Sprague Dawley rats were divided into five groups; control, HFD, HFD with omega-3 FA, HFD with UCN1, and HFD with UCN1 and omega-3 FA. Food intake, body weight (BW), body mass index (BMI), Lee index, glucose, insulin, HOMA-IR, triglycerides, cholesterol, low (LDL) and high (HDL) density lipoproteins, fibrinogen, plasminogen activator inhibitor 1 (PAI-1), fibrin degradation product (FDP), clotting time, bleeding time, prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet aggregation were measured. Food intake, BW, BMI, Lee index, glucose, insulin, HOMA-IR, triglycerides, cholesterol, LDL, fibrinogen, platelet aggregation, PAI-1, and FDP increased while bleeding and clotting times, PT, and aPTT decreased in HFD rats. UCN1 decreased food intake, BW, BMI, Lee index, bleeding and clotting times, PT, and aPTT and increased fibrinogen, PAI-1, FDP, and platelet aggregation in HFD rats. Omega-3 FA decreased food intake, BW, BMI, Lee index, platelet aggregation, glucose, insulin, HOMA-IR, triglycerides, and increased HDL and bleeding time in HFD rats. We concluded that UCN1 worsens the hypercoagulable state in HFD rats while omega-3 FA improve the insulin resistance and decrease the platelet aggregation in those rats.     

Omega-6 and omega-3 fatty acids metabolism pathways in the body of pigs fed diets with different sources of fatty acids

This study was carried out on 24 gilts (♀ Polish Large White × ♂ Danish Landrace) grown with body weight (BW) of 60 to 105 kg. The pigs were fed diets designed on the basis of a standard diet (appropriate for age and BW of pigs) where a part of the energy content was replaced by different fat supplements: linseed oil in Diet L, rapeseed oil in Diet R and fish oil in Diet F (6 gilts per dietary treatment). The fat supplements were sources of specific fatty acids (FA): in Diet L α-linolenic acid (C18:3 n?3, ALA); in Diet R linoleic acid (C18:2 n?6, LA) and in Diet F eicosapentaenoic acid (C20:5 n?3, EPA), docosapentaenoic acid (C22:5 n?3, DPA) and docosahexaenoic acid (C22:6 n?3, DHA). The protein, fat and total FA contents in the body did not differ among groups of pigs. The enhanced total intake of LA and ALA by pigs caused an increased deposition of these FA in the body (p < 0.01) and an increased potential body pool of these acids for further metabolism/conversions. The conversion efficiency of LA and ALA from the feed to the pig’s body differed among groups (p < 0.01) and ranged from 64.4% to 67.2% and from 69.4% to 81.7%, respectively. In Groups L and R, the level of de novo synthesis of long-chain polyunsaturated FA was higher than in Group F. From the results, it can be concluded that the efficiency of deposition is greater for omega-3 FA than for omega-6 FA and depends on their dietary amount. The level of LA and ALA intake influences not only their deposition in the body but also the end products of the omega-3 and omega-6 pathways.