Aberrant PCK-related reactions may lead to a series of pathological conditions, including obesity and dysregulation of glucose metabolism.7 Adipose-specific Pck1 knockout mice lacked glyceroneogenesis, and exhibit a lipodystrophic form of metabolic syndrome,34,35 while adipose-specific Pck1 overexpressing mice exhibit increased glyceroneogenesis and decreased circulating fatty acid.36,37 The broad biological functions of PCK1, besides just gluconeogenesis, prompted us to further investigate whether PCK2 could also regulate bone development via metabolic pathways. Here, PCK1 is linked to obesity due to melanocortin 4 receptor deficiency.