CTBP2 and obesity due to melanocortin 4 receptor deficiency: Since CtBP2 activation in hepatocytes downregulated gluconeogenic and lipogenic gene expression in vitro (Figs. 1f and 3j) and the activity of CtBP2 is diminished in obesity (Fig. 3e–i and Supplementary Fig. 4f), we investigated whether exogenous supplementation of CtBP2 can improve the metabolic profile of obese mice in vivo (Supplementary Fig. 7a).