The beta 3-adrenergic receptor (B3AR) is a member of the super-family of G protein-coupled receptor superfamily. They are characterized by seven putative transmembrane helices connected by hydrophilic loops. The mechanism by which the activated beta ARs transmit the signals across the plasma membrane involves the stimulation of Gs. This stimulation in turn activates adenyl cyclase. Activation of adenyl cyclase yields the second messenger cAMP. B3AR is primarily present in adipocytes. B3AR plays a significant role in the control of lipolysis and thermogenesis in the brown adipose tissue of rodents and humans. In human B3AR, a Trp to Arg replacement has recently been discovered at position 64. This change in the first coding exon has been correlated with increased weight gain, difficulty in losing weight, insulin resistance syndrome, and worsened diabetic situation. Higher percentages of this mutation are observed in Pima Indians (over 30%) and Japanese (20%). Chronic stimulation of the B3AR by highly selective B3AR agonist CL316,243, induces ectopic expression of UCP1 in adipose tissues and skeletal muscle. This expression may contribute to the potent anti-obesity effect of the beta 3-adrenergic agonist. Human B3AR is a 408aa membrane protein (rat/mouse, 400aa). The N-terminus is predicted to be extracellular; the C-terminus intracellular.