Central leptin regulates the UCP1 and ob genes in brown and white adipose tissue via different β-adrenoceptor subtypes

Abstract

The three known subtypes of β-adrenoreceptors (β1-AR, β2-AR, and β3-AR) are differentially expressed in brown and white adipose tissue and mediate peripheral responses to central modulation of sympathetic outflow by leptin. To assess the relative roles of the β-AR subtypes in mediating leptin's effects on adipocyte gene expression, mice with a targeted disruption of the β3-adrenoreceptor gene (β3-AR KO) were treated with vehicle or the β1/β2-AR selective antagonist, propranolol (20 μg/g body weight/day) prior to intracerebroventricular (ICV) injections of leptin (0.1 μg/g body weight/day). Leptin produced a 3-fold increase in UCP1 mRNA in brown adipose tissue of wild type (FVB/NJ) and β3-AR KO mice. The response was unaltered by propranolol in wild type mice, but was completely blocked by this antagonist in β3-AR KO mice. In contrast, ICV leptin had no effect on leptin mRNA in either epididymal or retroperitoneal white adipose tissue (WAT) from β3-AR KOs. Moreover, propranolol did not block the ability of exogenous leptin to reduce leptin mRNA in either WAT depot site of wild type mice. These results demonstrate that the β3-AR is required for leptin-mediated regulation of ob mRNA expression in WAT, but is interchangeable with the β1/β2-ARs in mediating leptin's effect on UCP1 mRNA expression in brown adipose tissue.