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

The three known subtypes of beta -adrenoreceptors (beta (1)-AR, beta (2)-AR, and beta (3)-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 P-AR subtypes in mediating leptin's effects on adipocyte gene expression, mice with a targeted disruption of the beta (3)-adrenoreceptor gene (beta (3)-AR KO) were treated with vehicle or the beta (1)/beta (2)-AR selective antagonist, propranolol (20 mug/g body weight/day) prior to intracerebroventricular (ICV) injections of leptin (0.1 mug/g body weight/day). Leptin produced a 3-fold increase in UCP1 mRNA in brown adipose tissue of wild type (FVB/NJ) and beta (3)-AR KO mice. The response was unaltered by propranolol in wild type mice, but was completely blocked by this antagonist in beta (3)-AR KO mice. In contrast, ICV leptin had no effect on leptin mRNA in either epididymal or retroperitoneal white adipose tissue (WAT) from beta (3)-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 beta (3)-AR is required for leptin-mediated regulation of ob mRNA expression in WAT, but is interchangeable with the beta (1)/beta (2)-ARs in mediating leptin's effect on UCP1 mRNA expression in brown adipose tissue.