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  • Title: Metformin reverses fatty liver disease in obese, leptin-deficient mice.
    Author: Lin HZ, Yang SQ, Chuckaree C, Kuhajda F, Ronnet G, Diehl AM.
    Journal: Nat Med; 2000 Sep; 6(9):998-1003. PubMed ID: 10973319.
    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.
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