Central leptin regulates the UCP1 and ob genes in brown and white adipose tissue via different beta-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 sympatheti c outflow by leptin, To assess the relative roles of the P-AR subtypes in m ediating leptin's effects on adipocyte gene expression, mice with a targete d disruption of the beta (3)-adrenoreceptor gene (beta (3)-AR KO) were trea ted with vehicle or the beta (1)/beta (2)-AR selective antagonist, proprano lol (20 mug/g body weight/day) prior to intracerebroventricular (ICV) injec tions of leptin (0.1 mug/g body weight/day). Leptin produced a 3-fold incre ase 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, b ut was completely blocked by this antagonist in beta (3)-AR KO mice. In con trast, ICV leptin had no effect on leptin mRNA in either epididymal or retr operitoneal white adipose tissue (WAT) from beta (3)-AR KOs, Moreover, prop ranolol 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 expr ession in WAT, but is interchangeable with the beta (1)/beta (2)-ARs in med iating leptin's effect on UCP1 mRNA expression in brown adipose tissue.