Obese mice are resistant to insulin and IFNα. Treatment of ob/ob mice with metformin (MTF) decreased PTP-1B activity and restored insulin and IFNα sensitivity. C57BL/6J, ob/ob mice, and mice fed with a high fat diet (HFD) were treated with IFNα2a, metformin, or both as indicated under “Experimental Procedures.” A, shown are concentrations of TNFα in liver tissue of the 12 groups of mice. B, shown is total Akt and serine phosphorylated Akt (pAkt) in the liver before (basal) and 15 min after injecting 0.5 units/Kg insulin intraperitoneally. C, shown is 2′,5′OAS gene expression. D, shown is Mx gene expression. E, shown is PTP-1B gene expression. F, shown is PTP-1B activity. *, p<0.05; ***, p < 0.001 as compared with control mice. NS, not significant.