FOXO1 and obesity due to melanocortin 4 receptor deficiency: Additionally, the protein PGC-1α together with FOXO1—a crucial regulatory transcriptional factor in various metabolic processes—play critical roles in the development of obesity, insulin resistance, and type 2 diabetes (Asher and Schibler, 2011; Housley et al., 2009), supporting the notion that the hepatic SIRT1-PGC-1α/FOXO1 axis is part of the classic metabolic sensing network.