Open AccessNonobese mice with nonalcoholic steatohepatitis fed on a choline‐deficient, l ‐amino acid‐defined, high‐fat diet exhibit alterations in signaling pathways
Author(s) -
SuzukiKemuriyama Noriko,
Abe Akari,
Nakane Sae,
Uno Kinuko,
Ogawa Shuji,
Watanabe Atsushi,
Sano Ryuhei,
Yuki Megumi,
Miyajima Katsuhiro,
Nakae Dai
Publication year - 2021
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13272
Subject(s) - nonalcoholic steatohepatitis , choline , steatohepatitis , nonalcoholic fatty liver disease , chemistry , signal transduction , biochemistry , endocrinology , amino acid , medicine , biology , fatty liver , disease
Nonalcoholic steatohepatitis (NASH) is often associated with obesity, but some patients develop NASH without obesity. The physiological processes by which nonobese patients develop NASH and cirrhosis have not yet been determined. Here, we analyzed the effects of dietary methionine content on NASH induced in mice fed on a choline‐deficient, methionine‐lowered, l ‐amino acid‐defined high‐fat diet (CDAHFD). CDAHFD with insufficient methionine induced insulin sensitivity and enhanced NASH pathology, but without obesity. In contrast, CDAHFD with sufficient methionine induced steatosis, and unlike CDAHFD with insufficient methionine, also induced obesity and insulin resistance. Gene profile analysis revealed that the disease severity in CDAHFD may partially be due to upregulation of the Rho family GTPases pathway and mitochondrial and nuclear receptor signal dysfunction. The signaling factors/pathways detected in this study may assist in future study of NASH regulation, especially its ‘nonobese’ subtype.