One of candidate genes for an association with obesity is the heterotrimeric G proteins, which are key components of intracellular signal transduction and play a focal role in adipogenesis.2,35,36 A previous study showed that the GNB3 825C/T variant influences lipolysis.37 In the heterotrimeric G protein complex, the β subunit of the G protein complex is common for both Gs and Gi complexes, and is ubiquitously expressed.38 Therefore, a functional variation in GNB3 may influence the action of Gs- as well as Gi-coupled receptors. Here, GNB3 is linked to obesity due to melanocortin 4 receptor deficiency.