Metformin reverses fatty liver disease in obese, leptin-deficient mice
Metformin reverses fatty liver disease in obese, leptin-deficient mice
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DOI：
10.1038/79697
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发表时间：
2000-09-01
期刊：
影响因子：
82.9
通讯作者：
Diehl, AM
中科院分区：
文献类型：
--
作者：
Lin, HZ;Yang, SQ;Diehl, AM
脂肪肝是慢性肝病的常见病因，目前还没有已知的治疗方法。然而，由于它与高胰岛素血症和胰岛素抵抗有关，胰岛素增敏剂可能是有益的。为了评估这种可能性，对患有脂肪肝的胰岛素抵抗ob/ob小鼠进行了二甲双胍治疗，二甲双胍是一种改善肝脏胰岛素抵抗的药物。二甲双胍可改善脂肪肝，逆转肝脏肿大、脂肪变性和转氨酶异常。其治疗机制可能涉及抑制肝脏肿瘤坏死因子α和肿瘤坏死因子诱导因子的表达，从而促进肝脏脂质堆积和ATP耗竭。这些发现提示了二甲双胍的作用机制，并确定了胰岛素抵抗状态下的新治疗靶点。
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.