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To investigate the effects of metformin on fatty livers in insulin-resistant rats.Thirty-one male Wistar rats were randomly divided into a normal (n=8) and an experimental group (n=23). The normal group rats were fed a standard diet, and those of the experimental group with a high-fat diet. After 8 weeks, 7 rats from the experimental group were sacrificed to verify whether the model was established successfully. Then the experimental group was randomly subdivided into two groups: one with metformin treatment (n=8) and one without (n=8). After 6 weeks, insulin sensitivity was measured with glucose infusion rate (GIR) by euglycermic hyperinsulinemia clamp technique. Aminotransferase, triglyceride (TG) and free fatty acids (FFA) were measured by biochemical methods, insulin by radioimmunoassay and tumor necrosis factor-alpha (TNF alpha) by ELISA. The steatosis changes and inflammation activity of all rat livers were scored histologically.Compared with the model group, the insulin resistance, liver index, visceral adiposity and weight loss of the metformin group were dramatically ameliorated. The steatosis and the inflammatory activity in the livers and the level of serum aminotransferase of the metformin group were also significantly decreased. Furthermore, metformin treatment lowered serum TG, liver lipid accumulation and the production of FFA and TNF alpha.Metformin can significantly improved insulin resistance and fatty liver development in rats fed a high-fat diet. It may become a new choice for fatty liver treatment in the future.

To create a rat insulin resistant fatty liver model.14 male Wistar rats were randomly divided into a model and a control group. The model rats were fed a high-fat diet (45% of energy from fat) for 8 weeks, and the control group a standard diet (19% of energy from fat). Insulin sensitivity was measured with glucose infusion rate (GIR) by the euglycermic hyperinsulinemia clamp technique. The aminotransferase, triglyceride (TG), free fatty acid (FFA), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by biochemical methods, and insulin was measured by radioimmunoassay. The histological and ultrastructural changes of all rat livers were scored using light and electron microscopy.Rats fed the high-fat diet developed panlobular macrovesicular steatosis, lobular inflammatory cell infiltration and abnormal mitochondria, whereas those fed the standard diet had normal livers. All model group rats had elevated levels of aminotransferase, TG, FFA, insulin and liver index, and low GIR. In addition, the high-fat diet increased MDA and decreased SOD.A fatty liver and insulin resistance model was successfully developed in rats fed a high-fat diet for 8 weeks, which provided a useful experimental tool for elucidating pathogenesis and treatment of fatty liver.