Beta 3-adrenergic activation of adenylyl cyclase in mouse white adipocytes: modulation by GTP and effect of obesity.

Lipolysis and adenylyl cyclase (AC) activation in response to beta-adrenergic agents are abnormally low in white epididymal adipose tissue (WAT) of the ob/ob mouse. The abundance of G-proteins (Gs alpha and Gi alpha) linked to AC is also abnormally low. By contrast, beta-adrenergic receptor (beta-AR) levels were previously found to be normal in WAT and elevated in liver. The relative importance of various forms of the beta-AR in mouse WAT was reassessed in view of the discovery of the beta 3-AR. The results show that (1) the beta 3-AR is mainly responsible for AC activation in lean-mouse WAT; (2) the beta 3-AR is only partly responsible for AC activation in obese mouse WAT; and (3) GTP modulates beta 3--but not beta 1--or beta 2-AR activation of AC in a biphasic manner. Therefore, the beta 3-AR appears responsible for the well-known bimodal effect of GTP on beta-adrenergic receptor-mediated AC activity in WAT.