ACUTE INJECTION OF BETA-ADRENOCEPTOR AGONIST BRL-35135 CORRECTS BOTH IMPAIRED UNCOUPLING PROTEIN AND LIPOPROTEIN-LIPASE GENE-EXPRESSION BUTNOT HYPERCAPACITY OF LIPOGENESIS IN BROWN ADIPOSE-TISSUE OF SUCKLING FA FA RATS/

This study was undertaken to determine whether acute injection of the beta-adrenoceptor BRL 35135, which is known to activate thermogenesis, could correct the earliest detectable metabolic abnormalities that ch aracterize brown (BAT) and white (WAT) adipose tissues of pre-obese Zu cker rats. In 14-day-old pups, a single intraperitoneal injection of B RL (10 mu g/g, 3 h before sacrifice) had no effect on uncoupling prote in mRNA content in BAT of lean pups, whereas the low level of this mRN A was restored to normal in pre-obese rats. Both lipoprotein lipase (L PL) activity and mRNA content, which were decreased in BAT of pre-obes e compared to lean pups (-60%), were stimulated after BRL injection. H owever, this effect was more pronounced in fa/fa than in Fa/fa rats (100% and +50%, respectively). In BAT, the increase in fatty acid synth etase (FAS) activity observed in fa/fa rats compared to their lean Fa/ fa littermates was not reduced. In WAT, the stimulation of beta-adrene rgic receptors had no effect on lipid storage capacity, since FAS and LPL activities remained unchanged. In conclusion, pre-obese Zucker fa/ fa rats are responsive to BRL 35135 treatment: acute administration of this drug was able to improve impaired thermogenesis and to correct t emporarily other abnormalities of early emergence in BAT. This treatme nt had no effect in WAT. Taken together, our data reinforce the hypoth esis that reduced sympathetic activity in BAT is one of the primary le sions of the obese rat which may play a key role in the development of this genetic obesity.