Takashi Honda1, Masatoshi Ishigami2, Fangqiong Luo1, Ma Lingyun1, Yoji Ishizu1, Teiji Kuzuya1, Kazuhiko Hayashi1, Isao Nakano1, Tetsuya Ishikawa1, Guo-Gang Feng3, Yoshiaki Katano4, Tomoya Kohama5, Yasuyuki Kitaura5, Yoshiharu Shimomura5, Hidemi Goto1, Yoshiki Hirooka1. 1. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 2. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: masaishi@med.nagoya-u.ac.jp. 3. Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Japan. 4. Department of Gastroenterology, Banbuntane Hotokukai Hospital, Fujita Health University School of Medicine, Nagoya, Japan. 5. Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
Abstract
BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels.
BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels.
Authors: Nicole E Cummings; Elizabeth M Williams; Ildiko Kasza; Elizabeth N Konon; Michael D Schaid; Brian A Schmidt; Chetan Poudel; Dawn S Sherman; Deyang Yu; Sebastian I Arriola Apelo; Sara E Cottrell; Gabriella Geiger; Macy E Barnes; Jaclyn A Wisinski; Rachel J Fenske; Kristina A Matkowskyj; Michelle E Kimple; Caroline M Alexander; Matthew J Merrins; Dudley W Lamming Journal: J Physiol Date: 2017-12-27 Impact factor: 5.182
Authors: Kara Wegermann; Ricardo Henao; Anna Mae Diehl; Susan K Murphy; Manal F Abdelmalek; Cynthia A Moylan Journal: PLoS One Date: 2018-09-28 Impact factor: 3.240