Effect of 7 days administration of the [beta]-adrenoceptor agonist, brl 35135, on the development of obesity in suckling zucker (fa/fa) rats. Charon, C., F. Dupuy, V. Marie, and R. Bazin. Institut National de la Sant[acute]e et de la Recherche M[acute]edicale, U177. 15 rue de l'Ecole de M[acute]edecine, 75270 Paris Cedex 06, France.
APStracts 2:0005E, 1995.
This study was undertaken to determine whether administration of a thermogenic [beta]-agonist drug to Zucker fatty rats, could correct some of the earliest metabolic defects detectable in brown adipose tissue (BAT). Fa/fa and fa/fa littermates were given oral administration of BRL 35135 from 8 to 16 days of age. In fa/fa rats, the lipid content of white and brown adipose tissues was significantly reduced. In the BAT of fa/fa rats, thermogenic capacity was restored to the level observed in Fa/fa rats, while hyperactivity of fatty acid synthetase was abolished and a deficit in lipoprotein lipase (activity and mRNA) was partly corrected. Hyperinsulinemia in fa/fa pups was significantly reduced. The decreased content of GLUT4 mRNA that characterized BAT of fa/fa pups was also restored to normal. At variance with observations in preobese rats, BRL had very little or no effect on lean Fa/fa rats. The present study reveals that chronic administration of a [beta]-agonist drug early in life prevents emergence of most of the metabolic abnormalities that characterize fa/fa rats at the onset of obesity. This suggests that impaired sympathetic activity may play a role in the development of this genetic obesity. 

Received 16 August 1994; accepted in final form 12 January 1995.
APS Manuscript Number E0326-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 February 1995.