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Am J Physiol Endocrinol Metab 268: E1039-E1045, 1995;
0193-1849/95 $5.00
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AJP - Endocrinology and Metabolism, Vol 268, Issue 6 E1039-E1045, Copyright © 1995 by American Physiological Society

ARTICLES

Effect of the beta-adrenoceptor agonist BRL-35135 on development of obesity in suckling Zucker (fa/fa) rats

C. Charon, F. Dupuy, V. Marie and R. Bazin
Institut National de la Sante et de la Recherche Medicale, U177, Paris, France.

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, whereas 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 GLUT-4 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.


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