THERMOGENESIS IN BROWN ADIPOSE-TISSUE WITH AGE - POSTRECEPTOR ACTIVATION BY FORSKOLIN

beta(3)-Adrenergic-stimulated thermogenesis in brown adipose tissue (B AT) is diminished with age. beta(3)-Adrenergic receptors are positivel y coupled to adenylyl cyclase in BAT. To determine whether thermogenes is, in response to direct activation of adenylyl cyclase, is also impa ired with age, we examined whole body oxygen consumption, mitochondria l guanosine diphosphate (GDP) binding and BAT mitochondrial uncoupling protein (UPC) mRNA levels in 4- and 24-month-old F-344 rats following forskolin administration. We also examined the forskolin-induced chan ge in body temperature in 4-month-old rats. Tn some instances, the res ults were compared with administration of the specific beta(3)-adrener gic agonist, CGP-12177. Forskolin (3.5 mg/kg) increased oxygen consump tion but decreased body temperature. In subsequent experiments the BAT was unilaterally denervated. In these rats, the forskolin-(1.8 mg/kg) stimulated increase in oxygen consumption was similar in young and ol d rats. Forskolin increased GDP binding and UCP mRNA levels in both th e denervated and innervated BAT pads, The increases were equal or grea ter in the BAT from senescent rats. These findings, coupled with our p revious report of an impaired CGP-12177-stimulated increase in GDP bin ding in senescent rats, suggests beta(3)-adrenergic-stimulated, but no t post-receptor-stimulated, thermogenesis is diminished with age.