Antiobesity Effect of Eicosapentaenoic Acid in High-Fat/High-Sucrose Diet–Induced Obesity

Abstract

OBJECTIVEGiven the pleiotropic effect of eicosapentaenoic acid (EPA), it is interesting to know whether EPA is capable of improving obesity. Here we examined the anti-obesity effect of EPA in mice with two distinct models of obesity.RESEARCH DESIGN AND METHODSMale C57BL/6J mice were fed a high-fat/high-sucrose diet (25.0% [w/w] fat, 32.5% [w/w] sucrose) (HF/HS group) or a high-fat diet (38.1% [w/w] fat, 8.5% [w/w] sucrose) (HF group) for 4–20 weeks. A total of 5% EPA was administered by partially substituting EPA for fat in the HF/HS + EPA and HF + EPA groups.RESULTSBoth the HF/HS and HF groups similarly developed obesity. EPA treatment strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in HF/HS-fed mice (HF/HS + EPA group), where hepatic triglyceride content and lipogenic enzymes are increased. There is no appreciable effect of EPA on body weight in HF-fed mice (HF + EPA group) without enhanced expression of hepatic lipogenic enzymes. Moreover, EPA is capable of reducing hepatic triglyceride secretion and changing VLDL fatty acid composition in the HF/HS group. By indirect calorimetry analysis, we also found that EPA is capable of increasing energy consumption in the HF/HS + EPA group.CONCLUSIONSThis study is the first demonstration that the anti-obesity effect of EPA in HF/HS-induced obesity is associated with the suppression of hepatic lipogenesis and steatosis. Because the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data suggest that EPA is suited for treatment of the metabolic syndrome.

In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease

“…The particular HFD we selected has been well established to induce hepatic steatosis in a number of mouse strains (61,62). As expected, at the end of the 8-wk feeding period, the HFD mice showed significant increases in body weight (ca.…”

“…document significant glucose intolerance and metabolic changes in similar diet-dependent mouse models at this time point (61,62). As an additional control, because of differences in copper in normal diet and HFD, parallel experiments were performed in L-Luc mice fed low-fat diets (LFDs) with equivalent copper levels to the HFD.…”

Relationship between Coronary Artery Disease and Non-HDL-C, and Effect of Highly Purified EPA on the Risk of Coronary Artery Disease in Hypercholesterolemic Patients Treated with Statins: Sub-Analysis of the Japan EPA Lipid Intervention Study (JELIS)

“…It is possible that EPA suppressed liver lipogenesis associated with metabolic syndrome. Recently, Sato et al reported that in mice given a high-fat/high-sucrose diet, EPA suppressed sterol regulatory element binding protein-1, fatty acid synthase, and SCD-1 in the liver 31) , indicating that EPA was appropriate for the treatment of metabolic syndrome as it suppressed hepatic lipogenesis and steatosis. Further clinical trials are needed to investigate the relationship between EPA treatment and the development of metabolic syndrome.…”

“…In addition, the results may reflect the anti-arteriosclerosis effects of EPA, such as anti-platelet aggregation 32,33) , plaque stabilization 34,35) , anti-inflammation 31,[36][37][38][39] nitric oxide production 40,41) , small-dense LDL 38) and remnant-like particle cholesterol 42,43) -lowering effects.…”

Omega-3 Fatty Acid Improve Non Alcoholic Fatty Liver Induced by High Fat Diet in Rats.

“…The standard normal chow diet (ATMID Company, Egypt) consists of soybean, Corn, soybean oil, calcium carbonate, dicalcium phosphate, sodium chloride, lecithin, methionine, and vitamin/mineral mixture. The high fat diet consists of 25% fat "beef tallow" + 10% sucrose + 20% corn starch + 45% normal chow with 30% sucrose in drinking water according to [10] with modification.…”