Metformin Prevents and Reverses Inflammation in a Non-Diabetic Mouse Model of Nonalcoholic Steatohepatitis

Metformin Prevents and Reverses Inflammation in a Non-Diabetic Mouse Model of Nonalcoholic Steatohepatitis

フォーマット:

論文

責任表示:

Kita, Yuki ; Takamura, Toshinari ; Misu, Hirofumi ; Ota, Tsuguhito ; Kurita, Seiichiro ; Takeshita, Yumie ; Uno, Masafumi ; Matsuzawa-Nagata, Naoto ; Kato, Ken-ichiro ; Ando, Hitoshi ; Fujimura, Akio ; Hayashi, Koji ; Kimura, Toru ; Ni, Yinhua ; Otoda, Toshiki ; Miyamoto, Ken-ichi ; Zen, Yoh ; Nakanuma, Yasuni ; Kaneko, Shuichi

言語:

英語

出版情報:

Public Library of Science, 2012-09-18

著者名:

掲載情報:

PLoS ONE

ISSN:

1932-6203

巻:

7

通号:

9

開始ページ:

e43056

バージョン:

publisher

概要:

Background: Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes. We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model. Methodology/Principal Findings: Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient plus high fat (MCD+HF) diet with or without 0.1% metformin for … 8 weeks. Co-administration of metformin significantly decreased fasting plasma glucose levels, but did not affect glucose tolerance or peripheral insulin sensitivity. Metformin ameliorated MCD+HF diet-induced hepatic steatosis, inflammation, and fibrosis. Furthermore, metformin significantly reversed hepatic steatosis and inflammation when administered after the development of experimental NASH. Conclusions/Significance: These histological changes were accompanied by reduced hepatic triglyceride content, suppressed hepatic stellate cell activation, and the downregulation of genes involved in fatty acid metabolism, inflammation, and fibrogenesis. Metformin prevented and reversed steatosis and inflammation of NASH in an experimental non-diabetic model without affecting peripheral insulin resistance. © 2012 Kita et al. 続きを見る

URL:

http://hdl.handle.net/2297/32834

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受理日:	2012-09-18

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