title: Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 mice.
abstract: The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing with the growing epidemics of obesity and diabetes. NAFLD encompasses a clinicopathologic spectrum of disease ranging from isolated hepatic steatosis to NASH, which is a more aggressive form of fatty liver disease, to cirrhosis and, finally, hepatocellular carcinoma (HCC). The exact mechanism behind the development of HCC in NASH remains unclear; however, it has been established that hepatic steatosis is the important risk factor in the development of HCC. Metformin has recently drawn attention because of its potential antitumor effect. Here, we investigated the effects of metformin on high-fat diet (HFD)-induced liver tumorigenesis, using a mouse model of NASH and liver tumor. Metformin prevented long-term HFD-induced liver tumorigenesis in C57Bl/6 mice. Of note, metformin failed to protect against liver tumorigenesis in mice that had already begun to develop NAFLD. Metformin improved short-term HFD-induced fat accumulation in the liver, associated with the suppression of adipose tissue inflammation. Collectively, these results suggest that metformin may prevent liver tumorigenesis via suppression of liver fat accumulation in the early stage, before the onset of NAFLD, which seems to be associated with a delay in the development of inflammation of the adipose tissue.
authors: Department of Endocrinology and Metabolism.
authors: K
authors: K
authors: Tajima
authors: A
authors: A
authors: Nakamura
authors: J
authors: J
authors: Shirakawa
authors: Y
authors: Y
authors: Togashi
authors: K
authors: K
authors: Orime
authors: K
authors: K
authors: Sato
authors: H
authors: H
authors: Inoue
authors: M
authors: M
authors: Kaji
authors: E
authors: E
authors: Sakamoto
authors: Y
authors: Y
authors: Ito
authors: K
authors: K
authors: Aoki
authors: Y
authors: Y
authors: Nagashima
authors: T
authors: T
authors: Atsumi
authors: Y
authors: Y
authors: Terauchi
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D063646:Carcinogenesis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000517:prevention & control; D059305:Diet, High-Fat / Q000009:adverse effects; D018450:Disease Progression; D005234:Fatty Liver / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications; D011897:Random Allocation
chemical_list: D016588:Anticarcinogenic Agents; D007004:Hypoglycemic Agents; D008687:Metformin
keywords: adipose tissue inflammation; antitumor effect; liver tumorigenesis; metformin; nonalcoholic steatohepatitis