IMPAIRED BETA-ADRENERGIC RECEPTOR-MEDIATED REGULATION OF GENE-EXPRESSION IN ADIPOCYTES FROM OLDER RATS

With aging, in many cells there is a blunted capacity of beta-adrenerg ic agonists to increase adenosine 3',5'-cyclic monophosphate (cAMP) ac cumulation. We wondered if blunted cAMP responses led to impaired regu lation of genes in which expression is modified by cAMP. To test this hypothesis, adipocytes were isolated from 2- and 12- to 16-mo-old Spra gue-Dawley rats that were stimulated with isoproterenol, and the inhib itory effect on expression of genes for lipoprotein lipase (LPL) and f atty acid synthase (FAS) were examined. Isoproterenol-stimulated cAMP accumulation and glycerol release were impaired in adipocytes from the older rats. Isoproterenol inhibited expression of LPL and FAS mRNAs i n cells from the younger but not older rats. Removal of endogenous ade nosine partially restored isoproterenol-mediated inhibition of express ion of these genes in the cells. These results demonstrate that blunte d cAMP responses associated with aging in obese Sprague-Dawley rats le d to altered regulation of LPL and FAS genes. These findings extend th e possible physiological implications of impaired hormone-induced cAMP responses with aging.