Effects Of Dietary Fish Oil Research Articles

Dietary fish oil alleviates soleus atrophy during immobilization in association with Akt signaling to p70s6k and E3 ubiquitin ligases in rats

Reduced muscle activity leads to impaired insulin signaling, which leads to loss of contractile proteins and muscle mass via the Akt pathway. Dietary fish oil rich in long chain n-3 polyunsaturated fatty acids has been shown to prevent insulin signaling resistance in skeletal muscle. This study was conducted to elucidate the protective effect of dietary fish oil on disuse-induced perturbations in insulin signaling and soleus muscle atrophy. To accomplish this, rats were fed a corn-oil- (control) or fish-oil-based diet for 2 weeks, and then subjected to hindlimb immobilization while still receiving the same diets. After 10 days of immobilization, the soleus muscle mass and myosin heavy chain level had markedly decreased; however, these losses were significantly suppressed in rats fed dietary fish oil, compared with the control group. Dietary fish oil nearly completely attenuated the disturbances in activation of the Akt and p70 S6 kinase proteins, as well as the gene expression of muscle-specific E3 ubiquitin ligases (muscle atrophy F-box and muscle RING finger 1). However, insulin receptor substrate 1 associated with the p85 subunit of phosphoinositide 3-kinase was not altered during immobilization. Dietary fish oil also inhibited alterations in the gene expression of cyclooxygenase-2 and inducible nitric oxide synthase, with no additional observation of oxidative stress. Collectively, these findings indicate that dietary fish oil prior to and during immobilization may alleviate the immobilization-induced soleus muscle atrophy, at least in part, via the Akt pathway through E3 ubiquitin ligases and p70s6k.

Effects of Supplemental Fish Oil on Resting Metabolic Rate and Body Composition in Middle-Aged Adults

Several studies have shown that rodents accumulate less body fat when fed a diet rich in fish oil (FO) when compared to an iso-energetic diet rich in other types of fat. However, little is known about the effects of dietary FO on body composition and resting metabolic rate (RMR) in humans. PURPOSE: To determine the effects of supplemental FO on RMR and body composition in middle-aged adults. METHODS: A total of 24 middle-aged men and women (45+6y, mean+SD) participated in the study. All testing was performed first thing in the morning following an overnight fast. Baseline measurements of RMR were measured using indirect calorimetry using a facemask, and body composition was measured using air displacement plethysmography. Following baseline testing, subjects were randomly assigned in a double blind manner to one of two groups: 4g/d of Safflower Oil (SO); or 4g/d of FO supplying 1,600mg/d eicosapentaenoic acid (EPA) and 800mg/d docosahexaenoic acid (DHA). All tests were repeated following 6wk of treatment. Data were analyzed using a group X time repeated measures ANOVA. RESULTS: Compared to the SO group, there was a significant increase in lean mass following treatment with FO (FO= +0.48 + 0.5kg, SO= -0.05 + 0.6kg, p=0.03) and a significant reduction in fat mass (FO= -0.36 + 1.14kg, SO= +0.50 + 0.77kg, p=0.04) and body fat percentage (FO= -0.41 + 1.22% body fat, SO= +0.53 + 0.98% body fat, p=0.05). No significant differences were observed for body mass (FO= +0.11 + 0.83kg, SO= +0.46 + 0.75kg, p>0.05), RMR (FO= +17 + 260kcal, SO= -62 + 184kcal, p>0.05) or respiratory exchange ratio (FO= -0.02 + 0.09, SO= +0.02 + 0.05, p>0.05). CONCLUSION: 6wk of supplementation with FO in middle-aged adults significantly increased lean mass, and decreased fat mass and body fat percentage. However, there were no changes observed for RMR following FO supplementation. Supported by a Gettysburg College Research and Professional Development Grant and Genuine Health Corporation

N-3 PUFA-Enriched Diet Delays the Occurrence of Cancer Cachexia in Rat With Peritoneal Carcinosis

The aim of this study was to evaluate the effects of a fish oil (FO) diet (rich in long chain, n-3, polyunsaturated fatty acid) on cancer cachexia symptoms in rats. To this end, peritoneal carcinosis (PC) was generated by an intraperitoneal injection of cancer cells in BDIX rats fed FO or standard (Std) diets. Food intake and body weight were recorded throughout the study until sacrifice. PC rats were sacrificed when food intake was significantly and severely reduced. Fat and skeletal muscles masses were weighed and serum inflammatory cytokines concentration measured at sacrifice. Occurrence of anorexia in PC rats was delayed in the FO diet group (median time was multiplied by 2.5) in comparison with Std diet. At the time of sacrifice, PC rats displayed a lower body weight gain as well as lower muscle and fat masses than pair-fed rats, suggesting the presence of a hypermetabolism state. Serum TNF-α was significantly increased in PC rats compared with controls rats. There was no effect of FO diet on tissue mass (skeletal muscle and fat) or on TNF-alpha concentration. In conclusion, FO diet delays the appearance of anorexia induced by PC in rats.

Dietary fish oil decreases DNA adducts in the rat colon independent of estrogen status

Colon cancer is the third leading cause of cancer related death in men and women in the United States. Data from multiple studies show that dietary fish oil is associated with a decrease in colon cancer incidence. Estradiol (E2) has also been demonstrated to be protective against colon tumor formation and we have shown that E2 induces colonocyte apoptosis in conjunction with reducing formation of premalignant lesions. To date, however, possible relationships between estrogen status and the benefits of fish oil have not been thoroughly examined. We hypothesized that E2 could enhance the effects of dietary fish oil by additively decreasing DNA damage and increasing apoptosis. Dietary fish oil significantly decreased immunohistochemical staining intensity of O6‐methyldeoxyguanosine DNA adducts independent of the presence of E2 at 9h and 12h post treatment with carcinogen. E2 resulted in a significant increase in apoptosis independent of diet group at 12h post carcinogen, most notably in the luminal third of the crypts. Fish oil was not associated with an increase in apoptosis. These data are important because they demonstrate that fish oil is protective against DNA damage in the colon regardless of E2 status. In addition, our data demonstrate that induction of apoptosis in colonocytes at the point of DNA damage may serve as a primary mechanism for how E2 suppresses colon tumor formation.Grant Funding Source: American Institute for Cancer Research

Porcine peroxisome proliferator-activated receptor δ mediates the lipolytic effects of dietary fish oil to reduce body fat deposition1

Peroxisome proliferator-activated receptor delta promotes fatty acid catabolism and energy expenditure in skeletal muscle and adipose tissues. A ligand for PPARdelta is required to activate PPARdelta function. Polyunsaturated fatty acids are potential ligands for PPARdelta activation. The current experiment was designed to determine the potential for PUFA, particularly from dietary fish oil, to activate porcine PPARdelta in vivo. Transgenic mice were generated to overexpress porcine PPARdelta in the adipose tissue. Mice were fed a high-saturated fat (13% beef tallow), or high-unsaturated fat (13% fish oil) diet, or a diet containing 4 mg/kg of a PPARdelta ligand (L165041) for 4 mo. Compared with beef tallow feeding, fish oil feeding reduced fat mass and decreased (P < 0.05) plasma triacylglycerol and FFA concentrations in the transgenic mice. Adipose tissue expression of genes involved in adipogenesis (i.e., lipoprotein lipase and adipocyte fatty acid-binding protein) was decreased in transgenic mice fed fish oil or the PPARdelta ligand. In the same mice, expression of the lipolytic gene, hormone-sensitive lipase was increased (P < 0.05). Fish oil feeding also stimulated expression of genes participating in fatty acid oxidation in the liver of transgenic mice compared with wild-type mice. Overall, these results indicate that PUFA may serve as natural and effective regulators of lipid catabolism in vivo and many of these effects may be generated from activation of PPARdelta.

Fish oil regulates cell proliferation, protect DNA damages and decrease HER-2/neu and c-Myc protein expression in rat mammary carcinogenesis

The aim of this study is to assess the effect of dietary fish oil (MaxEPA) on DNA-strand breaks, cell proliferation and anti-apoptotic protein expressions in rat mammary carcinogenesis. Eighty-one female Sprague-Dawley rats were divided into two parts, one for DNA-strand breaks study and the other for immunohistochemical study. Female Sprague-Dawley rats were treated with 7,12-dimethylbenz(alpha)anthracene (DMBA) (0.5 mg/0.2 ml corn oil/100 g body weight) by a tail vein injection. Rats were fed either fish oil or corn oil (0.5 ml/day/rat) by oral gavage. Fish oil-treated group showed significant protection against generation of single-strand breaks (SSBs) (56.1%, P < 0.05) but increased effect (72.3%, P < 0.05) was found in the corn oil-treated group when compared to DMBA control group. Furthermore, fish oil-treated group exhibited substantial decrease in Ki-67 (P < 0.05), HER-2/neu (P < 0.05) and c-Myc (P < 0.05) immunolabelling indices when compared to carcinogen counterpart. However, corn oil treatment resulted in significant increase in the above parameters. The above data support the role of n-3 PUFA as a preventive agent for DNA damages and a potential to inhibit mammary carcinogenesis.

Effects of dietary n-3 fatty acids on characteristics and lipid composition of ovine sperm

The fatty acid composition of sperm affects the fertilization rate. The objective was to investigate the effects of dietary fish oil (as a source of n-3 fatty acids) on semen quality and sperm fatty acid composition in sheep. Eight Zandi fat-tailed rams were randomly allocated into two groups and fed either a control diet or a diet supplemented with fish oil. Both diets were isocaloric and isonitrogenous and were fed for 13 weeks, starting in the middle of the breeding season. Semen samples were collected weekly and their characteristics evaluated by standard methods, whereas samples collected at the start and end of the study were assessed (gas chromatography) for sperm lipid composition. Mean (±s.e.m.) sperm concentrations (4.3 × 109 ± 1.3 × 108v. 3.9 × 109 ± 1.3 × 108 sperm/ml and percentages of motile (77.25 ± 3.34 v. 60.8 ± 3.34) and progressively motile sperm (74.13 ± 1.69 v. 62.69 ± 1.69) were significantly higher in the fish oil group than control. Dietary fish oil increased the proportion of docosahexaenoic acid (DHA, C22:6 n-3) in sperm fatty acid composition. We concluded that feeding fish oil as a source of n-3 fatty acids attenuated seasonal declines in semen quality in rams, perhaps through increased DHA in sperm.

Increased leptin storage with altered leptin secretion from adipocytes of rats with sucrose-induced dyslipidemia and insulin resistance: effect of dietary fish oil

This study examined the effect of long-term feeding a high-sucrose diet (SRD) on the modulation of rat adipocyte's leptin secretion and storage. For this purpose, we analyzed ( a) basal and insulin-stimulated leptin release and the role of isoproterenol and palmitate on insulin-stimulated leptin secretion, ( b) the correlation between leptin and glycerol released, ( c) the relationship between leptin contents and adiposity, and ( d) the effect of fish oil (FO) administration on the above parameters. Wistar rats were fed an SRD for 6 months. Whereas half the animals continued with SRD up to month 8, the other half was fed an SRD in which FO partially replaced corn oil from months 6 to 8. Total leptin release was reduced both basally and under insulin stimulation in SRD-fed rats. However, the ratio of leptin released after hormone stimulation to basal leptin levels was similar in the 3 dietary groups. Isoproterenol inhibited insulin-stimulated leptin release in the 3 groups, but the percentage was lower in the SRD. Palmitic acid mimicked the effect of isoproterenol. Leptin release from adipocyte of SRD-fed rats negatively correlated with glycerol release. Leptin store increased in fat pads of SRD and positively correlated with adiposity. Fish oil reduced leptin content and fat pad hypertrophy, and normalized basal lipolysis, leptinemia, and glucose homeostasis. This suggests that enhanced lipolysis and altered insulin sensitivity could play a role in the decrease of leptin released in SRD-fed rats. This is consistent with the reversion of all the alterations after FO administration.

Studies on the protective effect of dietary fish oil on uranyl-nitrate-induced nephrotoxicity and oxidative damage in rat kidney

Human and animal exposure demonstrates that uranium is nephrotoxic. However, attempts to reduce it were not found suitable for clinical use. Dietary fish oil (FO) enriched in ω-3 fatty acids reduces the severity of cardiovascular and renal diseases. Present study investigates the protective effect of FO on uranyl nitrate (UN)-induced renal damage. Rats prefed with experimental diets for 15 days, given single nephrotoxic dose of UN (0.5 mg/kg body weight) intraperitoneally. After 5 d of UN treatment, serum/urine parameters, enzymes of carbohydrate metabolism, brush border membrane (BBM), oxidative stress and phosphate transport were analyzed in rat kidney. UN nephrotoxicity was characterized by increased serum creatinine and blood urea nitrogen. UN increased the activity of lactate dehydrogenase and NADP-malic enzyme whereas decreased malate, isocitrate and glucose-6-phophate dehydrogenases; glucose-6-phophatase, fructose-1, 6-bisphosphatase and BBM enzyme activities. UN caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation, activities of superoxide dismutase, glutathione peroxidase and decreased catalase activity. Feeding FO alone increased activities of enzymes of glucose metabolism, BBM, oxidative stress and Pi transport. UN-elicited alterations were prevented by FO feeding. However, corn oil had no such effects and was not similarly effective. In conclusion, FO appears to protect against UN-induced nephrotoxicity by improving energy metabolism and antioxidant defense mechanism.

Defective Phagocytosis of Apoptotic Cells by Macrophages in Atherosclerotic Lesions of ob/ob Mice and Reversal by a Fish Oil Diet

The complications of atherosclerosis are a major cause of death and disability in type 2 diabetes. Defective clearance of apoptotic cells by macrophages (efferocytosis) is thought to lead to increased necrotic core formation and inflammation in atherosclerotic lesions. To determine whether there is defective efferocytosis in a mouse model of obesity and atherosclerosis. We quantified efferocytosis in peritoneal macrophages and in atherosclerotic lesions of obese ob/ob or ob/ob;Ldlr(-/-) mice and littermate controls. Peritoneal macrophages from ob/ob and ob/ob;Ldlr(-/-) mice showed impaired efferocytosis, reflecting defective phosphatidylinositol 3-kinase activation during uptake of apoptotic cells. Membrane lipid composition of ob/ob and ob/ob;Ldlr(-/-) macrophages showed an increased content of saturated fatty acids (FAs) and decreased omega-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) compared to controls. A similar defect in efferocytosis was induced by treating control macrophages with saturated free FA/BSA complexes, whereas the defect in ob/ob macrophages was reversed by treatment with eicosapentaenoic acid/BSA or by feeding ob/ob mice a fish oil diet rich in omega-3 FAs. There was also defective macrophage efferocytosis in atherosclerotic lesions of ob/ob;Ldlr(-/-) mice and this was reversed by a fish oil-rich diet. The findings suggest that in obesity and type 2 diabetes elevated levels of saturated FAs and/or decreased levels of omega-3 FAs contribute to decreased macrophage efferocytosis. Beneficial effects of fish oil diets in atherosclerotic cardiovascular disease may involve improvements in macrophage function related to reversal of defective efferocytosis and could be particularly important in type 2 diabetes and obesity.

Effects of dietary vegetable oil supplementation on fillet quality traits, chemical and fatty acid composition of African catfish (&amp;lt;i&amp;gt;Clarias gariepinus&amp;lt;/i&amp;gt;)

Abstract. The effects of dietary fish oil (FO), soybean oil (SO) and linseed oil (LO) (12 % crude fat content each) in African catfish (Clarias gariepinus) diets were tested on the fillet flesh quality, chemical and fatty acid (FA) composition, after 3 and 6 weeks of feeding. The bodyweight gain of fish and the fillet dry matter, crude protein and crude fat content was not different among the divergent treatments. High (&gt;20 %) total n3 FA supplementation significantly increased the moisture loss of fillet (FO, LO). Applying the simple FA dilution model (JOBLING 2004a, 2004b), the incorporation dynamics of the most largely dosed FAs were accurately predictable after 3 weeks (R² between observed and estimated data for total n3 FAs: FO 0.95, LO 0.73 and for α-linolenic acid, LO 0.97). In the fillet FA composition the metabolism of n3 acids was more pronounced. The large provision of α-linolenic acid (LO) had a pronounced effect on the longchain, polyunsaturated n3 FA proportions (eicosapentaenoic and docosapentaenoic acids), while no effect was experienced on docosahexaenoic acid. This study suggests that daily bodyweight gain is not, while fillet flesh quality and FA composition is slightly compromised when fish oil is substituted for vegetable oils.

Effects of dietary fish oil on thyroid hormone signaling in the liver

n−3 polyunsaturated fatty acids (PUFAs) present in fish oil (FO) potently decrease serum lipids, which is also an effect of thyroid hormones. Both PUFAs and thyroid hormones affect hepatic lipid metabolism, and here we hypothesized that a long-term diet rich in n−3 PUFAs would enhance thyroid hormone action in the liver. Female rats received isocaloric and normolipid diets containing either soybean oil (SO) or FO during lactation. Male offspring received the same diet as their dams since weaning until sacrifice when they were 11 weeks old. FO group, as compared to SO group, exhibited lower body weight since 5 weeks of age until sacrifice, with no alterations in food ingestion, lower retroperitoneal white fat mass and elevated inguinal fat mass relative to body weight, with unchanged water and lipid but reduced protein percentage in their carcasses. FO diet resulted in lower serum triglycerides and cholesterol. Serum total triiodothyronine, total thyroxine and thyrotropin were similar between groups. However, liver thyroid hormone receptor (TR) β1 protein expression was higher in the FO group and correlated negatively with serum lipids. Liver 5′-deiodinase activity, which converts thyroxine into triiodothyronine, was similar between groups. However, the activity of hepatic mitochondrial glycerophosphate dehydrogenase, the enzyme involved in thermogenesis and a well-characterized target stimulated by T3 via TRβ1, was higher in the FO group, suggesting enhancement of thyroid hormone action. These findings suggest that the increase in thyroid hormone signaling pathways in the liver may be one of the mechanisms by which n−3 PUFAs exert part of their effects on lipid metabolism.

Enrichment with long chain omega-3 fatty acids and sensory evaluation of chicken meat

N-3 fatty acids are essential for normal growth and development, and may play an important role in prevention of coronary artery disease, hypertension, diabetes, arthritis, other inflammatory and autoimmune disorders and cancer in humans (Simopoulos, 1999). Fatty acid profiles of broiler meat may be modified by adding fish oils to the diet (Lopez-Ferrer et al., 2001). When meat is enriched with PUFA, particularly n-3 long-chain fatty acids (C≥20), all sources of added vegetable oils seem to be less effective than marine oils (Bou. R et al., 2004). The purpose of this experiment was to study the effect of dietary fish oil on fatty acid composition of thigh and breast meat in broiler chickens.

Effects of dietary supplemental fish oil during the peripartum period on blood metabolites and hepatic fatty acid compositions and total triacylglycerol concentrations of multiparous Holstein cows

The objectives were to evaluate the effects of dietary fish oil on plasma metabolite, hepatic fatty acid composition, and total triacylglycerol concentrations. Multiparous Holstein cows (n=42) were completely randomized to 1 of 3 treatments at 3wk prepartum. Treatments were no supplemental lipid or supplemental lipid from either Energy Booster (Milk Specialties Co., Dundee, IL) or fish oil. Treatment diets were fed from −21d relative to expected date of parturition until 10d postpartum. Treatments were fed as a bolus before the a.m. feeding. The dose of lipid fed during the prepartum period was 250g, whereas approximately 0.92% of the previous day's dry matter intake was supplemented postpartum. Blood was collected 3 times weekly for determination of plasma metabolites. Liver biopsies were performed at 21 and 10d before expected date of parturition and 1 and 14d after parturition to determine fatty acid compositions and total triacylglycerol concentrations. Dry matter intake, milk yield, and loss of body weight or body condition score were not affected by supplementing the diet with lipid or by the source of lipid. Supplemental lipid tended to increase plasma glucose and decrease nonesterified fatty acids during the postpartum period. Furthermore, plasma β-hydroxybutyrate was reduced during the postpartum period in the lipid-supplemented treatments. However, source of supplemental lipid had no influence on any blood metabolite. Supplemental fish oil altered the fatty acid composition of liver phospholipids and triacylglycerols, decreasing total saturated fatty acids and increasing total n-3 and long-chain polyunsaturated fatty acids (>20 carbon fatty acids). Despite the altered fatty acid composition, hepatic total triacylglycerol concentrations were unaffected by supplemental fish oil. Furthermore, the improved metabolic profile following lipid supplementation did not decrease hepatic total triacylglycerol concentrations.

Effects of dietary fish oil and trans fat on rat aorta histopathology and cardiovascular risk markers

Fish oil and shortening have been suggested to have opposite effects on cardiovascular disease (CVD). This study investigated the effect of shortening and fish oil on CVD risk factors and aorta histopathology, and the association between risk factors and aorta histopathology. Male Wister rats (n=30) were fed an AIN-93G diet containing 20% fat in the form of fish oil, shortening, or soybean oil for 4 weeks. Total cholesterol (TC), triacylglyceride (TG), and C-reactive protein levels were significantly (P<0.001) lower in the fish oil than in soybean oil and shortening groups. HDL-cholesterol concentrations were significantly different (P<0.001) between groups. In addition, LDL-cholesterol levels were significantly (P<0.001) lower in the fish oil and shortening groups than in the soybean oil group. Insulin and glucose concentrations did not differ among groups. Effect of dietary fat on tissue fatty acid composition significantly differed in abdominal fat and brain compared with RBC, heart, kidney and liver. The aortic wall was significantly (P=0.02) thinner in the fish oil group than in the soybean oil and shortening groups. The aortic wall thickness was positively correlated with TG and TC, but negatively with EPA + DHA levels of all tissues. These results suggested that fish oil had protective effects on aorta histopathology by hypolipidemic action in this rat model.

Hepatic gene expression profiles in juvenile rainbow trout (Oncorhynchus mykiss) fed fishmeal or fish oil-free diets

Reducing the reliance on fishery by-products as amino acid and fatty acid sources in feeds for farmed fish is a major objective today. We evaluated the effect of dietary fish oil or dietary fishmeal replacement by vegetable oils and plant proteins respectively through analysis of hepatic transcriptomes in rainbow trout (Oncorhynchus mykiss). Fish were fed right from first feeding with diets based on plant by-products before being killed. We analysed the hepatic gene profile using trout cDNA microarrays (9K). Our data showed that seventy-one and seventy-five genes were affected after fish oil and fishmeal replacement respectively. The major part of modified gene expression coding for proteins of the metabolic pathways was as follows: (i) a lower level of expression for genes of energy metabolism found in fish after fishmeal and fish oil replacement; (ii) a lower level of gene expression for fatty acid metabolism (biosynthesis) in fish fed with vegetable oils; (iii) a differential expression of actors of detoxification metabolism in trout fed with vegetable oils; (iv) a lower level of expression of genes involved in protein metabolism in fish fed with plant proteins. Overall, our data suggest that dietary fish oil replacement is linked to a decreased capacity of fatty acid biosynthesis (fatty acid synthase) and variation of detoxification metabolism (cytochrome P450s) whereas dietary fishmeal replacement may depress protein metabolism in the liver as reflected by glutamine synthetase.

Dietary (n-3) Long-Chain Polyunsaturated Fatty Acids Inhibit Ischemia and Reperfusion Arrhythmias and Infarction in Rat Heart Not Enhanced by Ischemic Preconditioning

Ischemic preconditioning (IPC) and (n-3) PUFA are both cardioprotective. This study compared effects of dietary fish oil, IPC, and their interactions on heart function and injury during myocardial ischemia and reperfusion. Male Wistar rats were fed diets containing 10% wt:wt fat comprising either 7% high-docosahexaenoic acid (DHA) [22:6(n-3)] tuna fish oil + 3% olive oil [(n-3) PUFA]; 5% sunflower seed oil + 5% olive oil [(n-6) PUFA]; or 7% beef tallow + 3% olive oil [saturated fat (SF)] for 6 wk. In control experiments, isolated perfused hearts were subjected to 30-min regional ischemia and reperfused for 120 min. The IPC hearts were subjected to 3 cycles of 5-min global ischemia before the ischemia and reperfusion. Control (n-3) PUFA hearts had significantly lower heart rate, coronary flow, end diastolic pressure, maximum relaxation rate, and ischemic and reperfusion arrhythmias. In reperfusion, they had greater developed pressure and maximum relaxation rate and smaller infarct (10.9 ± 0.6% ischemic zone, n = 6) than (n-6) PUFA (47.4 ± 0.3%, n = 6) or SF (50.3 ± 0.3%, n = 6). Compared with control, IPC significantly improved heart function and reduced infarct in (n-6) PUFA (11.8 ± 0.4%, n = 6) and SF hearts (13.1 ± 0.1%, n = 6). Heart function and infarct [(n-3) PUFA 9.6 ± 0.1%, n = 6] did not differ among dietary IPC groups. Arrhythmias, significantly reduced by IPC in (n-6) PUFA and SF hearts, were significantly lower in (n-3) PUFA IPC hearts. Dietary fish oil induces a form of preconditioning, nutritional preconditioning, limiting ischemic cardiac injury, and myocardial infarction and endows cardioprotection as powerful as IPC, which provides no additional protection in (n-3) PUFA hearts.

Anticoagulant Effect of Dietary Fish Oil in Hyperlipidemia

In hyperlipidemia, dietary fish oil containing n-3 polyunsaturated fatty acids (PUFA) provokes plasma triacylglycerol lowering and hypocoagulant activity. Using APOE2 knock-in mice, the relation of these fish-oil effects with altered gene expression was investigated. Male APOE2 knock-in mice, fed regular low-fat diet, had elevated plasma levels of triacylglycerol and coagulation factors. Plasma lipids and (anti)coagulant factors reduced on feeding the mice with fish oil (n-3 PUFA) or, to a lesser degree, with sunflower seed oil (n-6 PUFA). The fish-oil diet provoked a 40% reduction in thrombin generation. Microarray (Affymetrix) and single-gene expression analysis of mouse livers showed that fish oil induced: (1) upregulation of genes contributing to lipid degradation and oxidation; (2) downregulation of genes of gamma-glutamyl carboxylase and of transcription factors implicated in lipid synthesis; (3) unchanged expression of coagulation factor genes. After fish-oil diet, vitamin K-dependent coagulation factors accumulated in periportal areas of the liver; prothrombin was partly retained in uncarboxylated form. Only part of the changes in gene expression were different from the effects of sunflower seed oil diet. The hypocoagulant effect of n-3 PUFA is not caused by reduced hepatic synthesis of coagulation factors, but rather results from retention of uncarboxylated coagulation factors. In contrast, the lipid-lowering effect of n-3 PUFA links to altered expression of genes that regulate transcription and fatty acid metabolism.

Dietary fish oil decreases secretion of T helper (Th) 1-type cytokines by a direct effect on murine splenic T cells but enhances secretion of a Th2-type cytokine by an effect on accessory cells

Dietary fish oil is considered to have anti-inflammatory effects based primarily on its effects on T-cell proliferation and IL-2 secretion. Its effects on the secretion of T helper (Th) 1-type cytokines vary and few studies have examined its effects on the secretion of Th2-type cytokines. In the present study, we examined the effects of dietary fish oil on the secretion of Th1 and Th2-type cytokines by splenocytes and the mechanism by which dietary fish oil affects Th2-type cytokine secretion. Mice were fed diets supplemented with 18 % fish oil (w/w) +2 % maize oil or 20 % maize oil for 6 weeks. Spleen cells, isolated splenic T cells and accessory cells (splenocytes depleted of T cells) were stimulated with anti-CD3/anti-CD28. The secretion of interferon (IFN)-gamma, TNF-alpha, IL-4 and IL-10 was measured by ELISA. Dietary fish oil decreased the secretion of IFN-gamma and TNF-alpha by total splenocytes and isolated T cells. In contrast, dietary fish oil increased the secretion of IL-4 by total splenocytes but had no effect on IL-4 secretion by isolated T cells. When isolated T cells were cultured with CD11b+ cells (mainly macrophages), cells from mice fed the fish oil diet secreted more IL-4 than cells from mice fed the maize oil diet. These results demonstrate that dietary fish oil directs cytokine secretion by splenocytes towards a Th2 phenotype and that the effects of dietary fish oil on the secretion of a Th2-type cytokine are mediated by its effect on CD11b+ accessory cells.

Dietary fish oil associated with increased apoptosis and modulated expression of Bax and Bcl-2 during 7,12-dimethylbenz( α)anthracene-induced mammary carcinogenesis in rats

The present study investigated the chemopreventive effect of dietary fish oil (Maxepa), rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on induction of apoptosis in mammary carcinogenesis model. Mammary carcinogenesis was initiated by a single, tail vein injection of 7,12-dimethylbenz( α)anthracene (DMBA) (0.5 mg/0.2 ml corn oil/100 g body weight) at 7 weeks of animal age. Ninety female Sprague–Dawley rats were divided into two parts: part one was used for histology and immunohistochemical study and part two for morphological analysis. Each part consists of three experimental groups having 15 animals, i.e., Group A (DMBA control), Group B (DMBA+fish oil) and Group C (DMBA+corn oil). Rats were fed either fish oil or corn oil (0.5 ml/day/rat) by oral gavage, 2 weeks prior to DMBA injection. Treatment was continued 25 weeks, studying histopathology, expression of Bax and Bcl-2 proteins by immunohistochemistry and apoptosis by TUNEL assay and morphological study at 36 weeks. Results showed that the fish oil-treated group exhibited a substantial increase in Bax ( p<0.05) immunolabelling and a reduction of Bcl-2 immunopositivity ( p<0.05), and increased TUNEL-positive apoptotic cells ( p<0.05); however, corn oil treatment did not show these beneficial effects toward mammary preneoplasia. We conclude that fish oil has the potential to play a significant role in limiting mammary tumourigenesis in vivo.