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- Title
Metformin reverses fatty liver disease in obese, leptin-deficient mice.
- Authors
Lin, H Z; Yang, S Q; Chuckaree, C; Kuhajda, F; Ronnet, G; Diehl, A M
- Abstract
There is no known treatment for fatty liver, a ubiquitous cause of chronic liver disease. However, because it is associated with hyperinsulinemia and insulin-resistance, insulin-sensitizing agents might be beneficial. To evaluate this possibility, insulin-resistant ob/ob mice with fatty livers were treated with metformin, an agent that improves hepatic insulin-resistance. Metformin improved fatty liver disease, reversing hepatomegaly, steatosis and aminotransferase abnormalities. The therapeutic mechanism likely involves inhibited hepatic expression of tumor necrosis factor (TNF) alpha and TNF-inducible factors that promote hepatic lipid accumulation and ATP depletion. These findings suggest a mechanism of action for metformin and identify novel therapeutic targets in insulin-resistant states.
- Publication
Nature medicine, 2000, Vol 6, Issue 9, p998
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/79697