Thermogenesis in brown adipose tissue with age: post-receptor activation by forskolin

beta3-Adrenergic-stimulated thermogenesis in brown adipose tissue (BAT) is diminished with age. beta3-Adrenergic receptors are positively coupled to adenylyl cyclase in BAT. To determine whether thermo- genesis, in response to direct activation of adenylyl cyclase, is also impaired with age, we examined whole body oxygen consumption, mitochondrial 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 change in body temperature in 4-month-old rats. In some instances, the results were compared with administration of the specific beta3-adrenergic agonist, CGP-12177. Forskolin (3.5 mg/kg) increased oxygen consumption 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 old rats. Forskolin increased GDP binding and UCP mRNA levels in both the denervated and innervated BAT pads. The increases were equal or greater in the BAT from senescent rats. These findings, coupled with our previous report of an impaired CGP-12177-stimulated increase in GDP binding in senescent rats, suggests beta3-adrenergic-stimulated, but not post-receptor-stimulated, thermogenesis is diminished with age.