THE BETA-3-ADRENOCEPTOR AGONIST ICI-D7114 IS NOT AS EFFICIENT ON REINDUCTION OF UNCOUPLING PROTEIN MESSENGER-RNA IN SHEEP AS IT IS IN DOGS AND SMALLER SPECIES

Adipose tissue in newborn lambs is brown, but within a few days it is transformed into white adipose tissue. In the same way, preadipocytes cultured in serum-free chemically defined medium achieve full differen tiation and express uncoupling protein (UCP), a marker of brown adipos e tissue, when isolated from perirenal adipose tissue of the newborn, whereas they no longer express UCP when isolated from older lambs. The effects of a chronic stimulation of adipose tissue by a novel beta3-a drenoceptor agonist (ICI D7114) on the maintenance after birth and on the reinduction in older lambs of UCP mRNA in adipose tissue were stud ied. Treatment of newborn lambs with this agonist for 25 d maintained a slight level of UCP mRNA in perirenal and pericardiac, but not in om ental and inguinal, adipose tissue depots. Preadipocytes isolated from perirenal adipose tissue of treated animals differentiated, in vitro, into adipocytes, but no UCP mRNA could be detected either in the abse nce or in the presence of the beta3-adrenoceptor agonist in the cultur e medium. Treatment of 1-mo-old lambs with ICI D7114 for 12 d restored UCP mRNA in perirenal and pericardiac adipose tissues of two of four treated lambs, but at a much lower level than in the same tissues at b irth. In both experiments, the final BW and the ADG of lambs treated w ith ICI D7114 were not statistically different from controls. These re sults are quite different from those obtained with the same beta3-adre noceptor agonist in dogs and rodents.