Metformin reverses fatty liver disease in obese, leptin-deficient mice
Author: ["Hui Zhi Lin","Shi Qi Yang","Christine Chuckaree","Francis Kuhajda","Gabriele Ronnet","Anna Mae Diehl"]
Publication: Nature Medicine
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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) α 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.
Cite this article
Lin, H., Yang, S., Chuckaree, C. et al. Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med 6, 998–1003 (2000). https://doi.org/10.1038/79697
