Selective knockout of the srebpf1 gene does not reduce the content of cholesterol and triglycerides in the livers of Western diet–fed ldlr−/− mice, although, significantly, these mice do display reduced plasma cholesterol and triglyceride levels, improving the atherogenic lipoprotein profile and reducing atherosclerosis.12 In contrast, in ob/ob mice, genetic ablation of Scap, which senses intracellular sterols and controls processing of all 3 precursor SREBPs into their nuclear forms, did prevent fatty liver.52 However, obesity, hyperinsulinemia, and hyperglycemia persisted. The gene discussed is SCAP; the disease is obesity due to melanocortin 4 receptor deficiency.