Stimulation and inhibition of lipolysis in isolated rat adipocytes: evidence for age-related changes in responses to forskolin and PGE1.
The ability of a number of hormones to activate cellular responses in a variety of cells declines with age. The mechanisms responsible for these alterations are complex and incompletely understood. Rat adipocytes have served as an important model to study blunted responses to stimulatory hormones which function by activating cAMP accumulation. We have previously found that the blunted lipolytic response of adipocytes from older rats to the beta adrenergic receptor agonist isoproterenol appeared to be due to a lessened ability of isoproterenol to activate cAMP accumulation. Further, the blunted response to isoproterenol was apparently caused by an accentuated inhibition of lipolysis, mediated by adenosine receptors activated by endogenously released adenosine. The present studies were designed to test and extend those conclusions. We have utilized forskolin to augment the cAMP accumulation that occurs in the presence of isoproterenol. Isoproterenol-activated lipolysis was greater in adipocytes from 2 month old rats compared with those from 12 month old rats (603 +/- 32 vs 450 +/- 29 nmol/10(5) cells/hr, P less than 0.01). However, in the presence of forskolin (10(-6) M), there was no significant difference in the response to isoproterenol between the two groups (646 +/- 23 vs 615 +/- 29 nmoles/10(5) cells/hr). As we had seen previously, the adenosine receptor agonist phenylisopropyladenosine more effectively inhibited lipolysis in the adipocytes from older rats. We now also find that PGE1 more efficaciously inhibits lipolysis in the cells from older rats. These data confirm that diminished cAMP accumulation in adipocytes from older rats appears to be a rate-limiting alteration in the regulation of lipolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Hoffman
B B
BB
Department of Medicine, Stanford University School of Medicine.
Chang
H
H
Reaven
G M
GM
D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011458:Prostaglandins E; D005576:Colforsin; D010660:Phenylisopropyladenosine; D000242:Cyclic AMP; D007545:Isoproterenol