β3-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 β-adrenergic agents are abnormally low in white epididymal adipose tissue (WAT) of the ob/ob mouse. The abundance of G-proteins (G_sα and G_iα) linked to AC is also abnormally low. By contrast, β-adrenergic receptor (β-AR) levels were previously found to be normal in WAT and elevated in liver. The relative importance of various forms of the β-AR in mouse WAT was reassessed in view of the discovery of the β₃-AR. The results show that (1) the β₃-AR is mainly responsible for AC activation in lean-mouse WAT; (2) the β₃-AR is only partly responsible for AC activation in obese mouse WAT; and (3) GTP modulates β₃—-but not β₁—-or β₂-AR activation of AC in a biphasic manner. Therefore, the β₃-AR appears responsible for the well-known bimodal effect of GTP on β-adrenergic receptor-mediated AC activity in WAT.