Adenylyl cyclase inhibitory pathway is differentially modified in rat white and brown fat by high-energy diets

Incubation of white adipose tissue (WAT) adipocytes from rats fed a high-energy diet (Exp group) with antilipolytic G(i)-coupled adenylyl cyclase inhibitory agonists, nicotinic acid (Nic) and N⁶-(L-2- phenylisopropyl)adenosine (PIA), resulted in lower cellular adenosine 3',5'- cyclic monophosphate (cAMP) levels than in stimulated adipocytes from rats fed a nutritionally balanced diet (Con group). In contrast to WAT, incubation of brown adipose tissue (BAT) adipocytes with Nic yielded higher cAMP levels in the Exp vs. Con rats. In both WAT and BAT adipocytes, pertussis toxin treatment abolished the differences in Nic- and PIA-inhibited cAMP formation between Exp and Con animals. Immunoblotting of adipocyte membranes indicated a lower content of G(i)α but not G₈α in BAT membranes of Exp vs. Con animals after 6 and 10 wk of feeding. No such differences were found in the G₈α or G(i)α contents of WAT membranes. Thus the inhibitory pathway of adenylyl cyclase is proposed to be sensitized in WAT and desensitized in BAT of rats fed high-energy diets. These modifications in sensitivity are in line with reduced cAMP and lipolysis in WAT and increased cAMP and thermogenesis in BAT during obesity.