With age, there are increases in adiposity, leptin mRNA in white adipose ti
ssue (WAT), and serum leptin levels in rats. beta(3)-Adrenergic agonists ar
e anti-obesity agents in rodents, and activation of beta(3)-adrenergic rece
ptors (beta(3)AR) mediates an acute decrease in food consumption, increased
thermogenesis in brown adipose tissue (BAT), increased lipolysis in WAT, a
nd suppression of leptin gene expression and serum leptin levels. Because b
eta(3)AR signal transduction is impaired with age in BAT and WAT, beta(3)AR
-mediated regulation of leptin, feeding behavior, and adiposity may also be
impaired with age. To test this hypothesis, we infused young (6 month) and
old (24 month) F344 x BN rats with the beta(3)AR agonist CL316,243 (1 mg k
g(-1) day(-1)) using osmotic minipumps for 7 days. Food intake, body mass,
adiposity, and serum leptin, as well as leptin, uncoupling protein 1 (UCP1)
, and lipoprotein lipase (LPL) mRNA in BAT or WAT were determined. In young
rats, CL316,243 infusion reduced body mass and adiposity, suppressed serum
leptin and leptin mRNA levels in WAT, induced UCP1 in WAT, and increased U
CP1 and LPL mRNA levels in BAT. Moreover, treatment with CL316,243 was asso
ciated with a marked but transient suppression of food intake. Most of the
responses elicited in the old rats with CL316,243 treatment were qualitativ
ely similar to those in the young rats, but blunted in magnitude. beta(3)AR
activation of adenylyl cyclase was also reduced in the aged rats. These da
ta suggest that, although CL316,243 is an effective agent in aged rats, the
maximum responses are reduced, suggesting that the impaired beta(3)AR sign
al transduction with age is a major determining factor in the reduced effec
tiveness of CL316,243 in older rats.