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Metformin reverses fatty liver disease in obese, leptin-deficient mice

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.

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Figure 1: Effect of metformin on fatty liver disease in ob/ob mice.
Figure 2: Effect of metformin treatment on food intake and body weight.
Figure 3: Effect of metformin on gene expression by white adipose tissue.
Figure 4: Effect of metformin on increased hepatic expression of TNFα mRNA in ob/ob mice.
Figure 5: Effect of metformin on TNFα–regulated gene products

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Correspondence to Anna Mae Diehl.

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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

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