Low-dose fish oil consumption prevents hepatic lipid accumulation in high cholesterol diet fed mice.
ABSTRACT We examined the effects of low-dose fish oil ingestion on hepatic lipid accumulation caused after high cholesterol feeding in C57BL/6J mice. The mice were fed purified experimental diets consisting of 20 energy % (en%) safflower oil (SO or SO/CH), 2 en% fish oil + 18 en% safflower oil (2FO or 2FO/CH), or 5 en% fish oil + 15 en% safflower oil (5FO or 5FO/CH) with or without 2 weight % (wt %) cholesterol for 8 weeks. Hepatic triglyceride and total cholesterol contents were significantly lower in groups that were fed diets containing fish oil and cholesterol than in those that were fed safflower oil and cholesterol. The hepatic mRNA levels of fatty acid synthase (FAS) were lower in groups fed cholesterol or fish oil. Fatty acid oxidation-related hepatic gene expressions were higher in fish oil-fed groups. Fecal cholesterol excretion was higher in all cholesterol-fed groups; cholesterol excretion was high in groups fed fish oil and cholesterol. These results suggest that low-dose fish oil diets improve lipid metabolism by modifying the expression of lipid metabolism-related genes in the liver and increasing fecal cholesterol excretion.
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ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.International journal of hepatology. 01/2012; 2012:950693.
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ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is defined as excess of fat in the liver. We investigated the effects of black soybean on the cholesterol metabolism and insulin resistance of mice fed high cholesterol/fat diets. Mice were randomly allocated into 4 groups that were fed different diets: the normal cholesterol/fat diet; high cholesterol/fat diets (HCD); and HCD with 1%, and 4% black soybean powder (1B-HCD, and 4B-HCD). Liver total cholesterol and triglyceride concentrations were significantly lower in the black soybean-supplemented groups than that in the HCD group. PCR revealed significantly lower hepatic SREBP2 and HMG-CoA reductase mRNA levels of black soybeansupplemented mice. Real-time PCR revealed significantly higher hepatic ABCA1 mRNA level of black soybean-supplemented mice, which may increase cholesterol efflux. Liver bile acids concentration was significantly high in the 4B-HCD group. Black soybean stimulated secretion of adiponectin, activation of pAMPK, and eliminated free fatty acids in the liver. Black soybean supplementation decreased MDA and nitrate level. The activities of SOD, catalase, and GPx were restored by black soybean supplementation. Our data strongly indicate that black soybean influences the balance between oxidative and antioxidative stress. We suggest that black soybean improves cholesterol metabolism, insulin resistance, and alleviates oxidative damage in NAFLD.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 07/2013; · 2.99 Impact Factor
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ABSTRACT: We examined the effects of fish oil (FO) on high-cholesterol diet-induced hepatic lipid accumulation and oxidative stress. Female C57BL/6J mice were fed diets consisting of safflower oil (SO), 1 en% FO (1FO), 2 en% FO (2FO), or 20 en% FO (20FO) with or without 2 weight% (wt%) cholesterol (SO/CH, 1FO/CH, 2FO/CH, and 20FO/CH groups, respectively) for 8 weeks. The hepatic triacylglyceride levels were significantly lower in the 2FO/CH and 20FO/CH groups than in the SO/CH group. The hepatic mRNAs of fatty acid oxidation-related genes were upregulated and the fatty acid synthesis-related genes were downregulated by the FO feeding. Adverse effects were not observed in the plasma levels of indicators of oxidative stress in response to the consumption of FO up to 20 en%. These results suggest that FO consumption in the range of 2-20 en% prevents hepatic lipid accumulation, thus improving lipid metabolism without causing oxidative stress.Prostaglandins Leukotrienes and Essential Fatty Acids 03/2013; · 2.73 Impact Factor