Inhibitory effect of metformin on TNF-α expression in hepatic tissue of OLETF rats

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 randomly assigned to two groups(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 were fed with placebo.Twenty-two weeks after treatment,we analyzed hepatic triglyceride level and measured expression of TNF-α by western-blot(protein) and quantitative RT-PCR(mRNA).Results Twenty-two weeks after treatment,the level of fasting glucose,insulin,triglyceride,free fatty acids(FFA) and hepatic triglyceride increased significantly in OLETF group as compared with LETO group.Western-blot method showed upregulated expression of TNF-α protein in OLETF group(1.57-fold vs LETO group,P0.05).At the mRNA level,expression of TNF-α was also significantly elevated in OLETF group(1.67-fold vs LETO group,P0.05).Metformin reduced the level of fasting glucose,insulin,FFA and hepatic triglyceride significantly in OLETF/M group.After treatment of metformin,the expressions of TNF-α protein andmRNA in hepatic tissue downregulated(protein: 59%,P0.05 and mRNA: 45%,P0.05)in OLETF/M group.Conclusion The therapeutic effects of metformin on insulin resistance and fatty liver disease are associated with significant suppression of TNF-α expression in hepatic tissue.