Asiatic Acid Ameliorates Hepatic Lipid Accumulation and Insulin Resistance in Mice Consuming a High-Fat Diet

作者:Yan Sheng Lei; Yang Hui Ting; Lee Yi Ju; Lin Chun Che; Chang Ming Hui; Yin Mei Chin*
来源:Journal of Agricultural and Food Chemistry, 2014, 62(20): 4625-4631.
DOI:10.1021/jf501165z

摘要

Effects of asiatic acid (AA) at 10 or 20 mg/kg/day upon hepatic steatosis in mice consuming a high-fat diet (HFD) were examined. AA intake decreased body weight, water intake, feed intake, epididymal fat, and plasma and hepatic triglyceride levels in HFD-treated mice (P %26lt; 0.05). HFD enhanced 2.85-fold acetyl coenzyme A carboxylase (ACC1), 3.34-fold fatty acid synthase (FAS), 3.71-fold stearoyl CoA desaturase (SCD)-1, 3.62-fold 3-hydroxy-3-methylglutaryl coenzyme A reductase, 2.91-fold sterol regulatory element-binding protein (SREBP)-1c, and 2.75-fold SREBP-2 expression in liver (P %26lt; 0.05). Compared with HFD groups, AA intake at two doses reduced 18.9-45.7% ACC1, 25.1-49.8% FAS, 24.7-57.1% SCD-1, and 21.8-53.3% SREBP-1c protein expression (P %26lt; 0.05). Histological results indicated AA intake at two doses reduced hepatic lipid accumulation and inflammatory infiltrate. HFD increased hepatic production of reactive oxygen species, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-a, as well as decreased hepatic glutathione content and glutathione peroxidase and catalase activities (P %26lt; 0.05). AA intake at two doses reversed these alterations (P %26lt; 0.05). AA intake suppressed 32.4-58.8% nuclear factor kappa (NF-kappa)B p65 and 24.2-56.7% p-p38 expression (P %26lt; 0.05) and at high dose down-regulated 29.1% NF-kappa B p50 and 40.7% p-JNK expression in livers from HFD-treated mice. AA intake at two doses lowered plasma insulin secretion and HOMR-IR (P %26lt; 0.05). These results suggest that AA is a potent hepatic protective agent against HFD-induced hepatic injury.