STIMULATION OF BROWN ADIPOSE-TISSUE BY BE TA(3)-ADRENOCEPTOR AGONISTS

In view to utilize beta3 adrenoceptor agonists for the investigation o f body lipid metabolism, a study of the effects of BRL 37344 on the fu nctional activity of the brown adipose tissue was performed in the Rat . It is known that this tissue is the principal site of heat productio n for nonshivering thermogenesis mainly due to the oxidation of fatty acids under the control of norepinephrine (NA) released from the sympa thetic nervous system. In order to stimulate the activity of the tissu e, rats were reared at 16-degrees-C. When they were one month old, the y were divided in two groups; one group received a surgical sympathect omy of the interscapular brown adipose tissue (TABI) (S group); the ot her group was sham-operated (T group). The resting metabolism was esti mated by the continuous measurement of O2 consumption and CO2 release, at an ambient temperature of 25-degrees-C. The animal capacity for no nshivering thermogenesis was determined by increased O2 consumption fo llowing i.p. administration of NA or BRL 37344. In the S group a large decrease in TABI NA content and a decrease in resting metabolism were observed. In both groups VO2 was increased by the two drugs; the incr ease was linearly related to the dose of BRL (between 2.5 to 10 mug/kg ); but it was 3 times as high in the T group as in the S group. Moreov er, the effect of BRL was 40 fold greater than the effect of NA. These results seem to indicate that, in cold reared rats, a part of nonshiv ering thermogenesis may be mediated by the beta3 receptors of the brow n fat. It may be concluded that the rats born in cold conditions are g ood models to study the role of beta3 receptors in the energetic activ ity of this tissue very profuse in infant but not in adult man.