DOWN-REGULATION OF BETA-3-ADRENERGIC RECEPTOR EXPRESSION IN RAT ADIPOSE-TISSUE DURING THE FASTED FED TRANSITION - EVIDENCE FOR A ROLE OF INSULIN/

The beta 3-adrenergic receptor (beta 3-AR) exerts a central role in th e transduction of catecholamine effects in white and brown adipose tis sue (WAT and BAT). A recent report has documented that insulin strongl y down-regulates beta 3-AR expression and catecholamine responsiveness in 3T3-F442A adipocytes [Feve, El Hadri, Quignard-Boulange and Pairau lt (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 5677-5681]. In the present report we show that the rise in plasma insulin levels elicited by the fasted/fed transition is associated with a reduction in beta 3-AR mRN A levels and beta-adrenergic responsiveness in WAT and BAT. beta 3-AR transcripts are also decreased in adipose tissue from animals subjecte d for 6 h to euglycaemic hyperinsulinaemic glucose clamps. Moreover, i nsulin acts directly on cultured rat white and brown adipocytes to dec rease beta 3-AR gene expression and adenylate cyclase activity in resp onse to beta 3-AR-selective agonists. These results suggest that there is a close relationship between food intake, plasma insulin levels an d beta 3-AR expression.