Mechanism of the age-related decrease of epinephrine-stimulated lipolysis in isolated rat adipocytes: beta-adrenergic receptor binding, adenylate cyclase activity, and cyclic AMP accumulation.

Abstract

beta-adrenergic binding ([3H]dihydroalprenolol), adenylate cyclase activity, and cAMP accumulation were measured in adipocytes to investigate whether the mechanism of decreased hormone-sensitive lipolytic response with age was mediated through membrane-associated events. The dose of epinephrine required for half maximal stimulation of glycerol release (ED50) was significantly lower in 2-month-old rats (0.8 +/- 0.2 microM)than in matur (6- and 12-month-old) rats (5.2 +/- 1.5 and 6.2 +/- 1.5 microM, respectively). In 24-month-old rats the ED50 (0.7 +/- 0.2 microM) was less than in mature rats. maximum rates of hormone-stimulated glycerol release (per 10(6) cells) was highest in the two mature groups and decreased by 50% in the old rats (P less than 0.01). Lipolytic changes were independent of cell size. beta-adreanergic raeceptor number (50-90 thousand sites/call) and affinity (KD 4-5 nM) were the same in each age group. ED50 and maximum level of hormone-stimulated adenylatae cyclase activity did not change with age. The ED50 of cAMP accumulation of young rats was 3 +/- 5 microM compared with 24 +/- 4 and 25 +/- 5 microM in 6- and 12-month-old rats, respectively. In old rats, the ED50 of cAMP accumulation was 2 +/- 1 microM (P less than 0.001 compared with mature rats). Maximally stimulated cAMP levels were the same in old and mature animals. Phosphodiesterase activity in the presence and absence of 10(-5) M isoproterenol did not change with age. The results suggest that age-related decrease of epinephrine-sensitive lipolysis in old rats may be due to alterations of the lipolytic pathway distal to the receptor-adenylate cyclase complex and the generation of cyclic AMP.