beta(3)-Adrenergic regulation of leptin, food intake, and adiposity is impaired with age

Citation
Mv. Kumar et al., beta(3)-Adrenergic regulation of leptin, food intake, and adiposity is impaired with age, PFLUG ARCH, 438(5), 1999, pp. 681-688
Citations number
29
Categorie Soggetti
Physiology
Journal title
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
ISSN journal
00316768 → ACNP
Volume
438
Issue
5
Year of publication
1999
Pages
681 - 688
Database
ISI
SICI code
0031-6768(199910)438:5<681:BROLFI>2.0.ZU;2-E
Abstract
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.