Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis.

Autor: Yuki Kita, Toshinari Takamura, Hirofumi Misu, Tsuguhito Ota, Seiichiro Kurita, Yumie Takeshita, Masafumi Uno, Naoto Matsuzawa-Nagata, Ken-Ichiro Kato, Hitoshi Ando, Akio Fujimura, Koji Hayashi, Toru Kimura, Yinhua Ni, Toshiki Otoda, Ken-ichi Miyamoto, Yoh Zen, Yasuni Nakanuma, Shuichi Kaneko
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: PLoS ONE, Vol 7, Iss 9, p e43056 (2012)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0043056
Popis: 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.
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