AJP - Endocrinology and Metabolism, Vol 266, Issue 4 E659-E665, Copyright © 1994 by American Physiological Society
Impaired beta-adrenergic receptor-mediated regulation of gene expression in adipocytes from older rats
L. Shilo, J. H. Chin and B. B. Hoffman
Department of Medicine, Stanford University School of Medicine, California.
With aging, in many cells there is a blunted capacity of beta-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.
