Background: Overnutrition of saturated fats and fructose is one of the major factors for the development of nonalcoholic fatty liver disease. Because omega-3 polyunsaturated fatty acids (n-3fa) have established lipid lowering properties, we tested the hypothesis that n-3fa prevents high-fat and fructose-induced fatty liver disease in mice. Methods: Male C57BL/6J mice were randomly assigned to one of the following diet groups for 14 weeks: normal diet (ND), high-fat lard-based diet (HFD), HFD with fructose (HFD + Fru), high-fat fish-oil diet (FOD), or FOD + Fru. Results: Despite for the development of obesity and insulin resistance, FOD had 65.3% lower (P < 0.001) hepatic triglyceride levels than HFD + Fru, which was blunted to a 38.5% difference (P = 0.173) in FOD + Fru. The lower hepatic triglyceride levels were associated with a lower expression of lipogenic genes LXRa and FASN, as well as the expression of genes associated with fatty acid uptake and triglyceride synthesis, CD36 and SCD1, respectively. Conversely, the blunted hypotriglyceride effect of FOD + Fru was associated with a higher expression of CD36 and SCD1. Conclusions: During overnutrition, a diet rich in n-3fa may prevent the severity of hepatic steatosis; however, when juxtaposed with a diet high in fructose, the deleterious effects of overnutrition blunted the hypolipidemic effects of n-3fa. ( J CLIN EXP HEPATOL 2016;6:265-274)

No abstract

Non-alcoholic fatty liver disease (NAFLD) is seen in 30-50% of type 2 diabetics and 80-90% of obese individuals. NAFLD is the result of hepatic insulin resistance causing an imbalance between lipogenesis and lipolysis. NAFLD is commonly treated by caloric restriction; however, the influence of continued high-fructose intake on NAFLD during weight loss remains unclear. The purpose of this study was to determine the lipogenic effects of high-fructose consumption on NAFLD during weight loss in obese mice. Male C57BL/6 mice were fed either a low-fat (LFD; 10% kcal fat) or high-fat (60% kcal fat) with 20% fructose solution (HFD+HF) for 8-weeks. Following 8-weeks, HFD+HF were randomly assigned to either LFD or LFD+HF to induce weight loss for 6-weeks. After 6-weeks, plasma was assayed for total cholesterol, triglyceride, glucose and HOMA-IR. Total lipid, triglyceride and cholesterol levels were quantified in hepatic tissues. An ANOVA was used to identify significant (P<0.05) differences between groups. HFD+HF caused obesity, insulin resistance and hyperlipidemia, as well as NAFLD (Table 1). Following weight loss, the LFD+HF HOMA-IR was similar to LFD mice; however, plasma triglyceride levels remained elevated. Although hepatic mass and percent total lipid were reduced following weight loss, hepatic triglyceride levels in the mice switched to LFD and LFD+HF were 2.2-and 3.0-fold greater, respectively than that found in the LFD control mice. These data suggest that during weight loss high fructose consumption did not impair insulin resistance. Although no difference was observed between either weight loss group for hepatic lipid metabolism and plasma cholesterol; however, hypertriglyceridemia was observed with high-fructose consumption.

High-fat high-fructose foods have been attributed to the development of hypertriglyceridemia and hepatic lipotoxicity. Hypertriglyceridemia represents an important marker for cardiovascular disease (CVD) risk and may play critical roles in the development of insulin resistance. Furthermore, cardiovascular dysfunction has been associated with increased hepatic lipid deposition. The hypotriglyceridemic effect of omega-3 fatty acids (n-3fa), found in Menhaden oil, may prevent high-fat high-fructose induced fatty liver disease. The purpose of this study was to determine if a high-fat Menhaden oil diet provides a therapeutic strategy for reducing CVD risk by altering hepatic lipid deposition. For 14-weeks, 8-week old male C57BL/6J mice were randomly assigned to: low-fat diet (LFD; 10% kcal fat), high-fat diet plus a 20% fructose solution (HFD+HF; 60% kcal fat), Menhaden oil diet with 20% fructose solution (MOD+HF) or Menhaden oil diet alone (MOD). Plasma was analyzed for total cholesterol, insulin, triglyceride, and glucose concentrations. To characterize hepatic lipotoxicity, tissue was analyzed for total lipid, triglyceride and cholesterol levels. Following the 14-weeks, the HFD+HF, MOD and MOD+HF diets (Table 1) developed obesity and diabetes. The addition of HF to the MOD diet resulted in significantly (P<0.05) elevated plasma cholesterol and triglyceride levels. The MOD+HF displayed a significantly (P<0.05) greater hepatic mass and hepatic cholesterol levels than the MOD and LFD groups. A high-fat Menhaden oil diet rich in n-3fa with or without HF does not prevent the imbalance in hepatic lipid metabolism normally found with obesity and type 2 diabetes.

No abstract