Chemical Genetic Identification of the Histamine H1 Receptor as a Stimulator of Insulin-Induced Adipogenesis

Alarge collection of bioactivecompoundswith diverse biological effects can be used as probes to elucidate new biological mechanisms that influence a particular cellular process. Here we analyze the effects of 880 well-known small-molecule bioactives or drugs on the insulin-induced adipogenesis of 3T3-L1 fibroblasts, a cell-culturemodelof fat cell differentiation. Our screen identified 86 compounds as modulators of the adipo- genic differentiation of 3T3-L1 cells. Examination of their chemical and pharmacological information re- vealed that antihistamine drugs with distinct chemical scaffolds inhibit differentiation. Histamine H1 receptor is expressed in 3T3-L1 cells, and its knockdown by small interferingRNAimpaired the insulin-induced ad- ipogenic differentiation. Histamine receptors and his- tamine-like biogenic amines may play a role in induc- ing adipogenesis in response to insulin.