In obesity and vitamin D metabolism-related gene networks, vitamin D receptor (VDR), cytochrome P450 gene family, i.e., CYP2R1, CYP24A1, and CYP27B1, are key players in vitamin D metabolism and interconnected with energy balance, adipocyte physiology, and adipokine secretion. This evidence concerns the gene CYP27B1 and obesity due to melanocortin 4 receptor deficiency.