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 the transduction of catecholamine effects in white and brown adipose tissue (WAT and BAT). A recent report has documented that insulin strongly down-regulates beta 3-AR expression and catecholamine responsiveness in 3T3-F442A adipocytes [Feve, El Hadri, Quignard-Boulange and Pairault (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 mRNA levels and beta-adrenergic responsiveness in WAT and BAT. beta 3-AR transcripts are also decreased in adipose tissue from animals subjected for 6 h to euglycaemic hyperinsulinaemic glucose clamps. Moreover, insulin acts directly on cultured rat white and brown adipocytes to decrease beta 3-AR gene expression and adenylate cyclase activity in response to beta 3-AR-selective agonists. These results suggest that there is a close relationship between food intake, plasma insulin levels and beta 3-AR expression.