As treatment of PerIRKO+/− mice with the PPARα agonist fenofibrate did not have an additive effect on lowering blood glucose or hepatic lipid content, this may indicate that reduced insulin signaling protects from hepatic steatosis by activating PPARα and AMPK signaling to alter hepatic lipid metabolism during conditions of metabolic overload. The gene discussed is PPARA; the disease is fatty liver disease.