HYPERTROPHY OF BROWN ADIPOCYTES IN BROWN AND WHITE ADIPOSE TISSUES AND REVERSAL OF DIET-INDUCED OBESITY IN RATS TREATED WITH A BETA(3)-ADRENOCEPTOR AGONIST

In a previous study, we demonstrated that chronic treatment with a new beta(3)-adrenoceptor agonist, CL 316,243 [disodium ydroxyethyl]-amino ]propyl]-1,3-benzodioxazole-2,2- dicarboxylate], promoted thermogenesi s, caused the appearance of multilocular adipocytes in white adipose t issue (WAT), and retarded development of obesity in young rats eating a high-fat diet (Himms-Hagen et al., Am J Physiol 266: R1371-R1382, 19 94). Objectives of the present study were to find out whether CL 316,2 43 could reverse established diet-induced obesity in rats and to ident ify the multilocular adipocytes that appeared in WAT. Infusion of CL 3 16,243 (1 mg/kg/day) reduced abdominal fat, with a decrease in enlarge d adipocyte size but no loss of white adipocytes. The resting metaboli c rate increased by 40-45%, but food intake was not altered. Abundant densely stained multilocular brown adipocytes expressing uncoupling pr otein (UCP) appeared in retroperitoneal WAT, in which a marked increas e in protein content occurred. UCP content of interscapular brown adip ose tissue (BAT) was also increased markedly. We suggest that the subs tantial increase in the resting metabolic rate induced by CL 316,243 o ccurs in brown adipocytes in both BAT and WAT. The origin of the brown adipocytes that appeared in WAT is uncertain. They may have been smal l brown preadipocytes, expressing beta(3)-adrenoceptors but with few m itochondria and little or no UCP, that were induced to hypertrophy by the beta(3)-agonist. (C) 1997 Elsevier Science Inc.