One strategy to counter obesity focuses on increasing kilocalories burned through heat production, or thermogenesis. Compared to white and brown adipose tissue thermogenesis, there has been relatively little effort to exploit thermogenic mechanisms in skeletal muscle. We previously showed muscle thermogenic induction by injecting the mixed melanocortin agonist, Melanotan II (MTII), into the ventromedial hypothalamus (VMH). MTII also activates sympathetic nervous system (SNS) outflow to skeletal muscle which leads us to hypothesize that the centrally induced muscle thermogenesis was mediated by SNS activation of skeletal muscle thermogenesis via beta-adrenergic receptor activation. Using the peripherally acting mixed beta antagonist, nadolol, we investigated the contribution of beta 1 and 2 receptors to muscle thermogenesis. Stereotaxic surgeries were performed on adult male rats (n=12) implanting a guide cannulae aimed at the VMH. Temperature transponders were also implanted in both hind limb gastrocnemius muscles. Rats were given intra-VMH microinjections of MTII or its vehicle (artificial cerebrospinal fluid) in combination with peripheral injections of either nadolol or its vehicle; muscle temperatures were measured before injection and each 30-minute interval after injection for 4 hours. Activation of brain melanocortin receptors significantly increased muscle temperature over 4 hours. Surprisingly, blocking beta-adrenergic receptors did not significantly change MTII-induced muscle thermogenesis. This contrasts with evidence from our laboratory that blocking peripheral beta adrenergic receptors diminishes the induction of muscle thermogenesis in alternative settings. The differential involvement of beta adrenergic receptors may help explain the distinct pattern and magnitude of muscle thermogenesis in other contexts.