Abstract: Objective To investigate the TNF-α expression in hepatic tissue of Otsuka Long-Evans Tokushima Fatty (OLETF) rats (an insulin resistance model) with abnormalities of glucose-lipid metabolism and effect of metformin on TNF-α expression. Methods OLETF rats were assigned to two groups randomly (OLETF and OLETF/M).The OLETF/M group was treated with metformin (100 mg/（kg·d)）, the OLETF group and age-matched LETO (nondiabetic Long-Evans Tokushima Otsuka rats) group was fed with placebo. After 22 weeks of treatment, we analyzed rats hepatic triglyceride levels and measured expression of TNF-αby western-blot (protein) and quantitative RT-PCR（mRNA). Results After 22 weeks of treatment, the levels of fasting glucose, insulin, triglyceride, free fatty acids (FFA) and hepatic triglyceride were increased significantly in OLETF group compared with LETO group. Western-blot method showed upregulated expression of TNF-α protein in OLETF group (1.57-fold vs LETO group, P <0.05). On the mRNA level, expression of TNF-α were also elevated significantly in OLETF group (1.67-fold vs LETO group, P <0.05). Metformin reduced levels of fasting glucose, insulin, FFA and hepatic triglyceride significantly in OLETF/M group. After treatment of metformin, the expressions of TNF-α protein and mRNA in hepatic tissue downregulated (protein: 59%, P<0.05 and mRNA: 45%, P<0.05)in OLETF/M group. Conclusion The therapeutic effects of metformin on insulin resistance and fatty liver disease were associated with the significant suppression of TNF-α expression in hepatic tissue.

Key words: metformin, TNF-α, insulin resistance, fatty liver disease