脂肪变性
内科学
内分泌学
甘油三酯
肝硬化
脂肪肝
非酒精性脂肪肝
肝损伤
肝纤维化
脂肪酸合酶
脂肪性肝炎
纤维化
生物
胆固醇
脂质代谢
化学
医学
疾病
作者
Takashi Honda,Masatoshi Ishigami,Fangqiong Luo,Li Ma,Yoji Ishizu,Teiji Kuzuya,Kazuhiko Hayashi,Isao Nakano,Tetsuya Ishikawa,Guo Feng,Yoshiaki Katano,Tomoya Kohama,Yasuyuki Kitaura,Yoshiharu Shimomura,Hidemi Goto,Yoshiki Hirooka
标识
DOI:10.1016/j.metabol.2016.12.013
摘要
For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis.In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH.Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation.Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (P<0.05). Moreover, hepatic total and free cholesterol of CDHF-BCAA was significantly lower than those of CDHF-control.BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels.
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