Beneficial Effects Of Fish Oil Research Articles

Integrated microbiome, metabolome and transcriptome profiling reveals the beneficial effects of fish oil and Bacillus subtilis jzxj-7 on mouse gut ecosystem.

The effects of fish oil (FO) and Bacillus subtilis jzxj-7 (JZXJ-7) on the colonic physiology, bacteria, metabolites, and gene expressions were studied in C57BL/6J mice. Co-administration of FO and JZXJ-7 was more beneficial than individual supplementation, as evidenced by improved growth performance, enhanced colon crypt depth and goblet cell numbers. FO + JZXJ-7 inhibited colonic fibrosis by downregulating fibrosis marker protein expression and upregulating occludin, claudin-2 and claudin-4 gene expressions. FO + JZXJ-7 ameliorated oxidative stress and inflammation by increasing catalase, superoxide dismutase, total anti-oxidation capacity, and reducing colon tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 levels. Mechanistically, FO + JZXJ-7 modulated the colon micro-ecological environment by enriching Roseburia, Lachnospiraceae NK4B4, Faecalibaculum and Lactococcus and its derived short-chain fatty acids, and activating Ppara and Car1 mediated peroxisome proliferators-activated receptor (PPAR) and phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling. Overall, FO + JZXJ-7 may serve as a promising nutraceutical to improve health by boosting the growth of colonic beneficial bacteria, altering metabolic phenotype, and regulating gene expression.

Investigation of the potential beneficial effects of fish oil against methotrexate-induced brain injury

Investigation of the potential beneficial effects of fish oil against methotrexate-induced brain injury

MyD88 determines the protective effects of fish oil and perilla oil against metabolic disorders and inflammation in adipose tissue from mice fed a high-fat diet

BackgroundThe beneficial effects of ω−3 polyunsaturated fatty acids (PUFA) vary between different sources. However, there is a paucity of comparative studies regarding the effects and mechanisms of marine and plant ω−3 PUFA on obesity.ObjectiveThe aim of this study was to evaluate the effects of fish oil (FO) and perilla oil (PO) on glucolipid metabolism, inflammation, and adipokine in mice fed a high-fat (HF) diet in association with the contribution of toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) pathway.MethodsC57BL/6J mice and MyD88−/− mice were randomly divided into 4 groups: normal chow diet, HF diet, HF diet accompanied by daily gavage with either FO or PO. After 4 weeks, blood biochemistries, adipocyte histology, mRNA, and protein expression of MyD88-dependent and -independent pathways of TLR4 signaling in epididymal adipose tissue were measured.ResultsIn C57BL/6J mice, there were no statistical differences between FO and PO in decreasing body weight, glucose, insulin, triglyceride, total cholesterol, interleukin-6, and increasing adipocyte counts. FO and PO decreased mRNA and protein expression of TLR4, MyD88, tumor necrosis factor receptor-associated factor 6, inhibitor of nuclear factor kappa B kinase beta and nuclear factor-kappa B p65. In MyD88−/− mice, the beneficial effects of FO and PO on HF diet-induced metabolism abnormalities and inflammation were abolished. FO and PO had no impacts on mRNA and protein expression of receptor-interacting protein-1, interferon regulate factor 3, and nuclear factor-kappa B p65.ConclusionFO and PO exhibit similar protective effects on metabolic disorders and inflammation through inhibiting TLR4 signaling in a manner dependent on MyD88. These findings highlight plant ω−3 PUFA as an attractive alternative source of marine ω−3 PUFA and reveal a mechanistic insight for preventive benefits of ω−3 PUFA in obesity and related metabolic diseases.

Beneficial effects of fish oil and cranberry juice on disease activity and inflammatory biomarkers in people with rheumatoid arthritis

ObjectivesWe sought to determine whether cranberry juice consumption would ameliorate laboratory and clinical measurements of disease activity in people with rheumatoid arthritis receiving fish oil supplementation. MethodsA prospective study was performed with 62 people with rheumatoid arthritis. We analyzed C-reactive protein modification of the Disease Activity Score-28 (DAS28-CRP) and inflammatory markers. The first group was assigned to eat their typical diet, a second group was asked to consume 3 g of fish oil ω-3 fatty acids daily, and a third group received both 3 g of fish oil n-3 fatty acids and 500 mL of reduced-calorie cranberry juice daily. ResultsCompared with baseline values, the group receiving both fish oil and cranberry juice showed reductions in erythrocyte sedimentation rate (P = 0.033), C-reactive protein (P = 0.002), DAS28-CRP (P = 0.001), adiponectin (P = 0.021), and interleukin-6 levels (P = 0.045), whereas the fish oil group showed decreased DAS28-CRP (P = 0.0261) and adiponectin (P = 0.0239). Differences across treatments showed that the group receiving both fish oil and cranberry experienced reductions (P < 0.05) in erythrocyte sedimentation rate and C-reactive protein compared to the control group and the group treated with fish oil alone, and a reduction in DAS28-CRP was verified when the fish oil and cranberry group was compared to the control group. ConclusionsThe ingestion of cranberry juice adds beneficial effects to fish oil supplementation, decreasing disease activity and inflammatory biomarkers in people with rheumatoid arthritis.

1H NMR Quantification of DHA and EPA in Fish Oil

Fish oil is a popular nutritional product consumed in China. The beneficial effects of fish oil have been attributed to docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Hence, it is crucial to develop a rapid and precise method to determine the contents of EPA and DHA in fish oil. In this study, a rapid and accurate proton nuclear magnetic resonance method for the quantification of DHA and EPA was developed. Dimethyl terephthalate was selected as an internal standard, and the signals at 2.391 ppm for DHA and at 1.697 ppm for EPA were chosen for the quantification. Validation of the method was performed in terms of specificity, precision, and stability. The results indicated that the method was precise and in line with the China Food and Drug Administration guidance. The method has been successfully applied to characterize fish oil capsules obtained from four pharmaceutical companies. This study indicated that the rapid 1H NMR method is suitable for the quality control of fish oil.

Dietary fish and ω-3 polyunsaturated fatty acids are associated with leukocyte ABCA1 DNA methylation levels.

A diet rich in fish and ω-3 polyunsaturated fatty acids (PUFAs) has been thought to reduce the risk for cardiovascular disease (CVD). The beneficial effects of fish oil and ω-3 PUFA on CVD can be mediated by epigenetic status of the genes associated with lipid metabolism and inflammation. The aim of this study was to investigate whether dietary fish and fatty acid (FA) intakes are associated with leukocyte ATP-binding cassette transporter A1 (ABCA1) DNA methylation levels in a Japanese population. This cross-sectional study included 298 adults (137 men and 161 women) without clinical history of CVD or cancer. The pyrosequencing method was used to measure leukocyte ABCA1 DNA methylation levels. Dietary fish and FA intakes were assessed based on the validated food frequency questionnaire. Mean ABCA1 DNA methylation levels were significantly lower in the highest fish intake groups (≥5-6/wk) compared with the lowest intake group (≤1-2/wk; P = 0.004). In multivariable linear regression analyses, higher dietary intake of ω-3 PUFAs and ω-3 highly unsaturated fatty acids was significantly associated with decreased levels of ABCA1 DNA methylation (P = 0.001 and 0.005); whereas no significant associations were seen between intake of dietary saturated fatty acid, monounsaturated fatty acid, and ω-6 PUFAs and ABCA1 DNA methylation. Higher dietary fish and ω-3 PUFA intake were associated with lower ABCA1 DNA levels in a Japanese population. The present results may bring potential insights on biological mechanisms underlying the protective effects of dietary fish and ω-3 PUFA intakes on CVD.

Beneficial effects of fish oil enriched in omega-3 fatty acids on the development and maintenance of neuropathic pain.

The aim of this work was to assess the preventive effect of an eicosapentaenoic acid/docosahexaenoic acid-concentrate fish oil on neuropathic pain development and regenerative features of sciatic nerve in rats. In the present study, rats with chronic constriction injury (CCI) of the sciatic nerve and sham-operated ones received fish oil enriched in omega-3 fatty acids (0.36 or 0.72g/kg per day, oral) or saline solution for 21days, with thermal hyperalgesia and mechanical allodynia being assessed before and 3, 7, 14 and 21days after injury. Fish oil enriched in omega-3 fatty acids (0.72g/kg) reversed thermal hyperalgesia and significantly reduced mechanical allodynia. In addition, ω-3 treatment (0.72g/kg) promoted the recovery of the Sciatic Functional Index as well as restored axonal density and morphology, without the formation of neuroma in the injured sciatic nerves after 21days. We conclude that the fish oil enriched in omega-3 fatty acids administration relieves thermal hyperalgesia and mechanical allodynia effectively and also enhances the recovery process in rats with CCI of the sciatic nerve. These findings might contribute to new therapeutic approaches including omega-3 fatty acids in neuropathic pain treatment.

Effect of using various amounts of patin (Pangasianodon hypophthalmus) fish oil on physical and chemical properties of moisturizing hand cream

Hand cream is used for rehydrating and improving skin properties. The skin is the first point of contact with the environment. Thus having healthy skin with proper barrier properties is quite important. The beneficial effects of fish oil on skin make it a favorable ingredient to be used in hand care products. In the present study, the efficacy and stability of various hand cream formulations using 0, 1.0, 2.5 and 5.0% of fish oil were investigated and compared. The appearance, odor, texture, and pH of formulations containing 1 and 2.5% of fish oil remained stable in very good qualities during the storage, whereas the related values to the appearance and texture of formulation containing 5.0% of fish oil at the end of 6 months of storage at 45°C were significantly (p<0.05) lower than other formulations and previous evaluations of this formulation. Weight loss was not observed in all formulations under study.

Благоприятное воздействие рыбьего жира на течение идиопатической гиперкальциурии у детей

Благоприятное воздействие рыбьего жира на течение идиопатической гиперкальциурии у детей

The effects of intermittent dietary supplementation with fish oil on high fat diet‐induced enhanced sensitivity to the behavioral effects of dopaminergic drugs

Eating a high fat diet can lead to obesity, type 2 diabetes, and dopamine system dysfunction. For example, rats eating high fat laboratory chow are more sensitive than rats eating standard chow to the behavioral effects of the dopamine receptor D2/D3 receptor agonist quinpirole. Specifically, quinpirole induces yawning in rats, and quinpirole‐induced yawning is enhanced in rats eating high fat chow as compared to rats eating standard chow. Daily dietary supplementation with 20% (w/w) fish oil prevents this high fat diet‐induced effect; however, for beneficial effects of fish oil in humans, doctors recommend that patients take fish oil only 2–3 times a week. To test the hypothesis that intermittent (e.g., 2/7 days per week) dietary supplementation with fish oil prevents high fat diet‐induced effects (e.g., weight gain and enhanced sensitivity to the behavioral effects of dopaminergic drugs) rats eating standard chow (17% kcal from fat), high fat chow (60% kcal from fat), and rats eating standard or high fat chow with 20% (w/w) intermittent (e.g., 2/7 days per week) dietary fish oil supplementation were tested once weekly with quinpirole (0.0032–0.32 mg/kg, i.p.) using a cumulative dosing procedure. Consistent with previous reports, eating high fat chow enhanced sensitivity of rats to the behavioral effects of quinpirole. That is, the quinpirole‐induced yawning dose‐response curve was shifted significantly to the left for rats eating high fat chow as compared to rats eating standard chow. Intermittent access to fish oil prevented this effect, since quinpirole‐induced yawning was not different among rats eating standard chow and rats eating high fat chow supplemented with fish oil. Future experiments will examine other dopaminergic drugs (e.g., cocaine) and will focus on understanding the mechanism by which fish oil produces these beneficial effects, by examining the specific omega‐3 polyunsaturated fatty acids found in fish oil.Support or Funding InformationA portion of this project was supported by R25 GM069621.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fish Oil-Containing Lipid Emulsions in Adult Parenteral Nutrition: A Review of the Evidence.

There is evidence from laboratory and animal studies that fish oil-containing intravenous lipid emulsions (FOC-IVLEs) have a beneficial effect on inflammation and the immune response, suggesting a possible clinical benefit. Clinical studies of FOC-IVLEs have reported mixed results. The aim of this review is to present findings from recent randomized controlled clinical trials and other quality clinical studies investigating the effects of administering intravenous fish oil alone or as part of a multilipid emulsion and to examine the quality of these studies in an objective, evidence-based manner. Studies comparing FOC-IVLEs with other IVLEs in adults were included. Thirty-four clinical studies were evaluated: 19 investigated levels of inflammatory and immune markers as an endpoint; 13 investigated rates of infection or sepsis; 3 investigated clinical outcomes in septic patients; and 29 investigated general clinical outcomes. There was conflicting evidence for a beneficial effect of fish oil on levels of inflammatory and immune markers and some evidence that fish oil decreased the rate of postoperative atrial fibrillation. Studies generally reported few statistical differences in clinical outcomes and rates of infection and sepsis with FOC-IVLEs as compared with other IVLEs. The quality of reporting was generally poor, and the presented evidence for comparisons between FOC-IVLEs and other IVLEs was inconclusive or weak. There is very little high-quality evidence that FOC-IVLEs have a more beneficial effect than other IVLEs on clinical outcomes in adult patients.

The Beneficial Effects of Fish Oil Following Cisplatin-Induced Oxidative and Histological Damage in Liver of Rats.

This study investigated the protective effect of fish oil (FO) on cisplatin (CP) toxicity in the rat liver. Twenty-eight rats were divided equally into four groups, with the first being a control group. The second group (CP group) was given 7 mg/kg of CP and the third group (FO group) was given 1 FO softgel/rat/day for 14 days. The rats in the fourth group (CP + FO group) were treated with both CP and FO at the above doses. CP treatment caused significant oxidative damage via an increase in thiobarbituric acid reactive substances (TBARS) and reduced antioxidant defenses through a decrease in the activities of catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione peroxidase (GPx) in rat liver tissue. Also, CP caused histopathological abnormalities, including necrosis, in the liver tissue. However, concurrent FO treatment prevented the negative oxidative and histopathological effects of CP. In conclusion, CP treatment can cause hepatotoxicity in rats, but dietary supplementation with FO can attenuate the oxidative and histological changes caused by CP. Thus, FO may be useful in preventing CP-induced hepatotoxicity in cancer patients.

The protective effect of fish oil against cisplatin induced eye damage in rats

Ocular toxicity induced by anticancer chemotherapy is not uncommon, but underestimated and under-reported. Visual changes have been attributed to a number of chemotherapeutic agents in humans. Cisplatin (CP), a heavy metal compound, is used in the treatment of many types of tumours. CP is known to produce nonspecific blurred vision, papilledema, and optic neuritis for high doses as well as cumulative dose regimens. The aim of this study was to investigate the possible beneficial effects of fish oil (FO) on eye tissue oxidative status and histological alterations against CP-induced in the rats. The animals were randomly divided into the following four groups: the control, CP, FO, and CP + FO groups. CP was intraperitoneally administered at the dose of 7 mg/kg and FO was orally given at 1 softgel per day for 14 days. The eye injury was assessed by biochemical and histological examinations. The levels of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were evaluated in the eye tissue. TBARS levels were significantly higher, the activities of the antioxidant enzyme and GSH levels were significantly lower in the CP group than in the control group. The histopathological evaluation also confirmed the foregoing findings. On the other hand, treatment of FO ameliorated the biochemical and histological alterations caused by CP. The results showed that treatment with FO may protect against the negative ocular effects of CP.

Postischemic fish oil treatment confers task-dependent memory recovery

A series of our previous studies demonstrated that fish oil (FO), equivalent to 300mg/kg docosahexahenoic acid (DHA), facilitates memory recovery after transient, global cerebral ischemia (TGCI) in the aversive radial maze (AvRM). The present study sought to address two main issues: (i) whether the memory-protective effect of FO that has been observed in the AvRM can be replicated in the passive avoidance test (PAT) and object location test (OLT) and (ii) whether FO at doses that are lower than those used previously can also prevent TGCI-induced memory loss. In Experiment 1, naive rats were trained in the PAT, subjected to TGCI (4-vessel occlusion model), and tested for retrograde memory performance 8 and 15days after ischemia. Fish oil (300mg/kg/day DHA) was given orally for 8days. The first dose was delivered 4h postischemia. In Experiment 2, the rats were subjected to TGCI, treated with the same FO regimen, and then trained and tested in the OLT. In Experiment 3, the rats were trained in the AvRM, subjected to TGCI, administered FO (100, 200, and 300mg/kg DHA), and tested for memory performance up to 3weeks after TGCI. At the end of the behavioral tests, the brains were examined for neurodegeneration and neuroblast proliferation. All of the behavioral tests (PAT, OLT, and AvRM) were sensitive to ischemia, but only the AvRM was able to detect the memory-protective effect of FO. Ischemia-induced neurodegeneration and neuroblast proliferation were unaffected by FO treatment. These results suggest that (i) the beneficial effect of FO on memory recovery after TGCI is task-dependent, (ii) doses of FO<300mg/kg DHA can protect memory function in the radial maze, and (iii) cognitive recovery occurs in the absence of neuronal rescue and/or hippocampal neurogenesis.

A fish oil diet induces mitochondrial uncoupling and mitochondrial unfolded protein response in epididymal white adipose tissue of mice

White adipose tissue (WAT) mitochondrial dysfunction is linked to the pathogenesis of obesity driven insulin resistance. Dietary conditions that alter fat mass are known to affect white adipocyte mitochondrial function, however, the impact of high calorie diets on white adipocyte mitochondria is not fully understood. The aim of this study is to assess the effect of a diet rich in saturated or polyunsaturated fat on mitochondrial unfolded protein response (UPRmt), a retrograde signaling response that maintains mitochondrial homeostasis, in epididymal WAT (eWAT). Mice were fed a low fat diet (LFD), saturated fat diet (SFD) or fish oil (unsaturated fat diet, UFD) and assessed changes in eWAT mitochondria. Compared to mice fed a LFD, SFD-fed mice have reduced mitochondrial biogenesis markers, mitochondrial fatty acid oxidation enzymes and TCA cycle enzymes, suggesting an impaired mitochondrial function that could contribute to increased fat mass. In contrast, isocaloric UFD-fed mice have increased expression of mitochondrial uncoupling protein 1 (UCP1) and peroxisomal fatty acid oxidation enzymes suggesting that elevated mitochondrial uncoupling and peroxisomal fatty acid oxidation could contribute to the reduction in fat mass. Interestingly, expression of UPRmt-associated proteins caseinolytic peptidase (ClpP) and heat shock protein 60 (Hsp60) are induced by UFD, whereas SFD reduced the expression of ClpP. Based on our data, we propose that induction of UPRmt helps to preserve a functional mitochondria and efficient utilization of fat by UFD whereas a dampened UPRmt response might impair mitochondrial function and promote fat accumulation by SFD. Thus, our findings suggest a potential role of UPRmt in mediating the beneficial effects of fish oil.

Oleic acid, hydroxytyrosol and n-3 fatty acids collectively modulate colitis through reduction of oxidative stress and IL-8 synthesis; in vitro and in vivo studies

Our recent study has demonstrated that medium chain triglycerides (MCT) and monounsaturated fatty acids potentiate the beneficial effects of fish oil on risk factors of cardiovascular disease. In the present study, we have investigated the influence of MCT or olive oil on the protective and mucosal healing ability of fish oil in ulcerative colitis using cell simulation and animal models. Caco-2 cells grown in medium chain fatty acids enriched medium has exaggerated t-butyl hydroperoxide induced cell damage, GSH depletion, and IL-1β induced IL-8 synthesis, compared to the cells grown in oleic acid & hydroxytyrosol (OT) enriched medium. Further, combined treatment of cells with eicosapentaenoic acid, docosahexaenoic acid, and OT has remarkably attenuated the cell damage, and IL-8 synthesis, compared to individual treatments. To evaluate the effect of these lipid formulations in vivo, adult Wistar rats were fed diet enriched with high amount of medium chain triglycerides (MCT), virgin olive oil, or their combination with fish oil. Colitis was induced in rats using dextran sulfate sodium (DSS) for 7days followed by 10-days of recovery period. Rats of MCT group exhibit severe disease activity, higher levels of inflammatory cytokines in the colon compared to the olive oil group. Furthermore, there was persistent body weight loss, loose stools, higher levels of inflammatory cytokines in the rats of MCT group, even after DSS was withdrawn from drinking water. Conversely, fish oil has remarkably attenuated the DSS induced alterations in both MCT and olive oil diet groups with significantly greater effect in the olive oil group. Thus, MCT increase the susceptibility to colitis through oxidative damage and IL-8 synthesis in intestinal epithelial cells. The beneficial effects of virgin olive oil could be partially attributed to hydroxytyrosol. Combined treatment of hydroxytyrosol, oleic acid and n-3 fatty acids exhibit huge therapeutic benefits in colitis.

Abstract 37: Effect of Fish Oil on Coagulation and Fibrinolysis: A Double-blind Randomized Trial in Obese Adolescents

Background: A hypercoagulable state is reported in obese children and adolescents. Fish oil may reduce the propensity for thrombosis by favorably impacting coagulation and fibrinolysis. We hypothesized that pharmacologic fish oil supplementation would reduce the concentration of coagulation factors such as total-fibrinogen (T-Fib) and gamma prime fibrinogen (γ’-Fib) and fibrinolysis factors such as plasminogen activator inhibitor-1 (PAI-1) in obese dyslipidemic adolescents. Methods: Participants (n=42, age 14±2 years) with hypertriglyceridemia and low-density lipoprotein (LDL) cholesterol &lt;160 mg/dL were enrolled in a randomized, doubleblind, crossover trial comparing 4 g of fish oil daily with placebo. Treatment interval was 8 weeks with a 4-week washout. Glucose, insulin, high-sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), T-Fib, γ’-Fib and PAI-1 were measured pre- and post-intervention or placebo. Results: PAI-1 significantly decreased (p = 0.03) with a trend towards a decrease in T-Fib in the fish oil group. Fish oil treatment group also showed significant decrease in γ’-Fib, but not in the placebo group; mean change (95% CI): -0.11 (-0.16, -0.06) vs -0.03 (-0.08, 0.02). The difference in the mean change in γ’-Fib concentration from baseline or washout measures between fish oil treatment and placebo was significant; reg coeff (SE):0.08 (0.03); p=0.02. The change in γ’-Fib was related to the change in log transformed PAI-1 (reg coeff (SE): -0.09 (.041); p=0.03). Further, log-transformed CRP and IL-6 (reg coeff (SE): 0.064 (.030), p=0.04) and 0.10 (.04); p=0.03 respectively) showed significant correlations with baseline or washout baseline γ’ fibrinogen, but there were no such relationships for mean changes. Conclusions: Fish oil-induced synchronized reduction of γ’-Fib, T-Fib and PAI-1 suggests attenuation of the obesity-related alterations in coagulation and fibrinolysis in adolescents. Intriguingly, these changes are independent of changes in other inflammatory factors. The reduction in elevated concentration of γ’-Fib is remarkable as it forms clots that are more fibrinolysis resistant. Further evaluation is warranted on the specific beneficial effect of fish oil on the obesity-related hypercoagulant-/hypofibrinolytic-state and the potential for thrombosis later in life.

Medium-chain triglycerides and monounsaturated fatty acids potentiate the beneficial effects of fish oil on selected cardiovascular risk factors in rats

Fish oil (FO) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is known to reduce the risk of cardiovascular diseases (CVDs). Little information is known regarding the influence of lipid composition in the background diet on the modulatory effect of FO supplementation on CVDs. The present study was designed to investigate the influence of various background dietary lipids and FO on selected cardiovascular risk factors in rats. Adult Wistar rats were fed semisynthetic diet with FO at 1.0% or 2.0% along with other lipids, namely, medium-chain triacylglycerols (MCTs), monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs) and n-3 PUFAs, for 5 weeks. Some of the potent CVD risk factors were estimated in the rats. FO at 1.0% and 2.0% has significantly reduced serum lipid peroxides, total cholesterol, triglycerides (TAGs), tumor necrosis factor-α, interleukin-6 and C-reactive protein; liver and adipose TAG and cholesterol levels in MCT, MUFA and n-6 PUFA diet groups. Notably, these alterations were comparatively higher in 1.0% FO-substituted MCT and MUFA diet groups. Interestingly, feeding of FO along with n-3 PUFAs did not show additive effect in attenuation of these factors. Serum liver EPA and DHA levels were remarkably elevated in rats fed FO-enriched MCT or MUFA diets. Our results suggest that MCTs or MUFAs in the background diet might promote the beneficial effects of FO on CVDs.

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.

PPARα-independent actions of omega-3 PUFAs contribute to their beneficial effects on adiposity and glucose homeostasis.

Excess dietary lipid generally leads to fat deposition and impaired glucose homeostasis, but consumption of fish oil (FO) alleviates many of these detrimental effects. The beneficial effects of FO are thought to be mediated largely via activation of the nuclear receptor peroxisomal-proliferator-activated receptor α (PPARα) by omega-3 polyunsaturated fatty acids and the resulting upregulation of lipid catabolism. However, pharmacological and genetic PPARα manipulations have yielded variable results. We have compared the metabolic effects of FO supplementation and the synthetic PPARα agonist Wy-14,643 (WY) in mice fed a lard-based high-fat diet. In contrast to FO, WY treatment resulted in little protection against diet-induced obesity and glucose intolerance, despite upregulating many lipid metabolic pathways. These differences were likely due to differential effects on hepatic lipid synthesis, with FO decreasing and WY amplifying hepatic lipid accumulation. Our results highlight that the beneficial metabolic effects of FO are likely mediated through multiple independent pathways.