title: Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice.
abstract: 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.
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: masaishi@med.nagoya-u.ac.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishigami
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Fangqiong
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Ma
authors.initials: M
authors.lastname: Lingyun
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ishizu
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Teiji
authors.initials: T
authors.lastname: Kuzuya
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Nakano
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Japan.
authors.forename: Guo-Gang
authors.initials: GG
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, Banbuntane Hotokukai Hospital, Fujita Health University School of Medicine, Nagoya, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Katano
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kohama
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kitaura
authors.affiliation: Laboratory of Nutritional Biochemistry, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Shimomura
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000627:therapeutic use*; D000818:Animals; D002784:Cholesterol / Q000097:blood; D002794:Choline / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000096:biosynthesis / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects*; D018450:Disease Progression; D060766:Drinking Water; D015870:Gene Expression / Q000187:drug effects; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000597:Amino Acids, Branched-Chain; D060766:Drinking Water; D002784:Cholesterol; D002950:Citrate (si)-Synthase; D002794:Choline
keywords: BCAA; Cholesterol; Fatty acid synthase; NASH; Steatosis