CtBP2 adopts a monomeric configuration in obese liver in response to an increase in fatty acyl-CoA content, resulting in the liberation of Forkhead box O1 (FoxO1) (21) and sterol regulatory element-binding protein 1 (SREBP1) (22) to concurrently activate hepatic gluconeogenesis and lipogenesis, a hallmark of obesity. The gene discussed is SREBF1; the disease is obesity due to melanocortin 4 receptor deficiency.