ADENYLYL-CYCLASE INHIBITORY PATHWAY IS DIFFERENTIALLY MODIFIED IN RATWHITE AND BROWN FAT BY HIGH-ENERGY DIETS

Incubation of white adipose tissue (WAT) adipocytes from rats fed a hi gh-energy diet (Exp group) with antilipolytic G(i)-coupled adenylyl cy clase inhibitory agonists, nicotinic acid (Nic) and N-6-(L-2-phenyliso propyl)adenosine (PLA), resulted in lower cellular adenosine 3',5'-cyc lic monophosphate (cAMP) levels than in stimulated adipocytes from rat s fed a nutritionally balanced diet (Con group). In contrast to WAT, i ncubation of brown adipose tissue (BAT) adipocytes with Nic yielded hi gher cAMP levels in the Exp vs. Con rats. In both WAT and BAT adipocyt es, pertussis toxin treatment abolished the differences in Nic- and PI A-inhibited cAMP formation between Exp and Con animals. Immunoblotting of adipocyte membranes indicated a lower content of G(i) alpha but no t G(s) alpha in BAT membranes of Exp vs. Con animals after 6 and 10 wk of feeding. No such differences were found in the G(s) alpha or G(i) alpha contents of WAT membranes. Thus the inhibitory pathway of adenyl yl 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.