AJP - Endocrinology and Metabolism, Vol 247, Issue 6 772-E777, Copyright © 1984 by American Physiological Society
Age-related decrement in hormone-stimulated lipolysis
B. B. Hoffman, H. Chang, Z. T. Farahbakhsh and G. M. Reaven
The ability of hormones to activate responses in a variety of tissues
decreases with age. The mechanism(s) responsible for these alterations are
unclear. We have confirmed that the ability of a beta-adrenergic receptor
agonist to activate lipolysis in isolated rat adipocytes decreases with
age. Maximum response to isoproterenol was greater in 2-mo-old rats (600
+/- 30 nmol of glycerol released/10(5) cells per h) than 12-mo-old rats
(250 +/- 25 nmol/10(5) cells per h), P less than 0.001. Similarly, ACTH is
less effective in activating lipolysis in the adipocytes from the older
rats. However, the cAMP analogue 8-(4-chlorophenothio)adenosine
3',5'-monophosphate cyclic activated lipolysis equally in the two groups,
suggesting that the deficit in adipocytes from the older rats was proximal
to cAMP-dependent protein kinase activation. Both isoproterenol and ACTH
were significantly less effective in promoting cAMP accumulation in
adipocytes isolated from 12-mo-old rats. There was no difference in
phosphodiesterase activity of the adipocytes between the two groups.
beta-Adrenergic receptors were measured using the antagonist radioligand
[125I]cyanopindolol. The number of beta-adrenergic receptors was actually
increased in the adipocytes from 12-mo-old rats (26,000 +/- 2,600
receptors/cell) compared with cells from 2-mo-old rats (7,200 +/- 1,300
receptors/cell). The results suggest that diminished cAMP production is
responsible for the diminished lipolytic response in the adipocytes of
older rats. The mechanism responsible for this change is uncertain but
cannot be explained by a loss in beta-adrenergic receptors.
