EFFECT OF THE BETA-ADRENOCEPTOR AGONIST BRL-35135 ON DEVELOPMENT OF OBESITY IN SUCKLING ZUCKER (FA FA) RATS/

This study was undertaken to determine whether administration of a the rmogenic 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-3 5135 from 8 to 16 days of age. In fa/fa rats, the lipid content of whi te 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 abolis hed, and a deficit in lipoprotein lipase (activity and mRNA) was partl y 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 pre obese rats, BRL had very little or no effect on lean Fa/fa rats. The p resent study reveals that chronic administration of a beta-agonist dru g early in life prevents emergence of most of the metabolic abnormalit ies that characterize fa/fa rats at the onset of obesity. This suggest s that impaired sympathetic activity may play a role in the developmen t of this genetic obesity.