title: Evaluation of Methionine Content in a High-Fat and Choline-Deficient Diet on Body Weight Gain and the Development of Non-Alcoholic Steatohepatitis in Mice.
abstract: OBJECTIVE
  Non-alcoholic steatohepatitis (NASH) is a globally recognized liver disease. A methionine- and choline-deficient diet is used to induce NASH in mice; however, this diet also causes severe body weight loss. To resolve this issue, we examined the effects of methionine content in a high-fat and choline-deficient (HFCD) diet on body weight and the development of NASH in mice.
  
  
  METHODS
  C57BL/6J mice (male, 10 weeks of age) were fed an L-amino acid rodent (control) diet, high-fat (HF) diet, or HFCD diet containing various amounts of methionine (0.1-0.6% (w/w)) for 12 weeks. Plasma lipid levels, hepatic lipid content and inflammatory marker gene expression were measured, and a pathological analysis was conducted to evaluate NASH.
  
  
  RESULTS
  The 0.1% methionine in HFCD diet suppressed body weight gain, which was lower than that with control diet. On the other hand, the 0.2% methionine in HFCD diet yielded similar body weight gains as the control diet, while more than 0.4% methionine showed the same body weight gains as the HF diet. Liver weights and hepatic lipid contents were the greatest with 0.1% methionine and decreased in a methionine dose-dependent manner. Pathological analysis, NAFLD activity scores and gene expression levels in the liver revealed that 0.1% and 0.2% methionine for 12 weeks induced NASH, whereas 0.4% and 0.6% methionine attenuated the induction of NASH by HFCD diet. However, the 0.2% methionine in HFCD diet did not induce insulin resistance, despite the body weight gain.
  
  
  CONCLUSIONS
  The 0.2% methionine in HFCD diet for 12 weeks was able to induce NASH without weight loss.
authors.affiliation: Information Center, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku-ku, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Information Center, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku-ku, Tokyo, Japan.
authors.forename: Sachina
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Information Center, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Food Science and Nutrition, Kinki University Faculty of Agriculture, Nakamachi, Nara, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Information Center, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku-ku, Tokyo, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Umegaki
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002794:Choline / Q000378:metabolism / Q000494:pharmacology; D059305:Diet, High-Fat; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D005951:Glucose Tolerance Test; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008715:Methionine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology*; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D008055:Lipids; D008715:Methionine; D002794:Choline