Impaired β-adrenergic receptor-mediated regulation of gene expression in adipocytes from older rats

With aging, in many cells there is a blunted capacity of β-adrenergic agonists to increase adenosine 3',5'-cyclic monophosphate (cAMP) accumulation. We wondered if blunted cAMP responses led to impaired regulation of genes in which expression is modified by cAMP. To test this hypothesis, adipocytes were isolated from 2- and 12- to 16-mo-old Sprague- Dawley rats that were stimulated with isoproterenol, and the inhibitory effect on expression of genes for lipoprotein lipase (LPL) and fatty 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 in cells from the younger but not older rats. Removal of endogenous adenosine partially restored isoproterenol-mediated inhibition of expression of these genes in the cells. These results demonstrate that blunted cAMP responses associated with aging in obese Sprague-Dawley rats led to altered regulation of LPL and FAS genes. These findings extend the possible physiological implications of impaired hormone-induced cAMP responses with aging.