Liver PPAR-α downregulation and substantial enhancement in the hepatic SREBP-1c/PPAR-α mRNA content ratio represent major metabolic disturbances between de novo lipogenesis and FA oxidation favouring the former, as a central issue triggering liver steatosis in obesity-induced oxidative stress and insulin resistance. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.