The beta-adrenergic receptors and the control of adipose tissue metabolismand thermogenesis

The beta -adrenergic receptors (beta ARs) are members of the large family o f G protein-coupled receptors. There are three beta AR subtypes (beta (1)AR , beta (2)AR beta (3)AR), each of which is coupled to Gas and the stimulati on of intracellular cAMP levels. While beta (1)AR and beta (2)AR are broadl y expressed throughout tissues of the body, beta (3)AR is found predominant ly in adipocytes. Stimulation of the beta ARs leads to lipolysis in white a dipocytes and nonshivering thermogenesis in brown fat. However, in essentia lly all animal models of obesity, the beta AR system is dysfunctional and t he ability to stimulate lipolysis and thermogenesis is impaired. Neverthele ss, we and others have shown that selective beta (3)AR agonists are able to prevent or reverse obesity and the loss of beta AR expression and to stimu late thermogenesis. This chapter will review the current understanding of t he role of the sympathetic nervous system and the adipocyte beta ARs in mod els of obesity; the physiologic impact of changes in beta AR expression on body composition and thermogenesis; and the regulation and unique propertie s of beta AR subtypes in brown and white adipocytes, The latter includes ou r recent discovery of novel signal transduction mechanisms utilized by beta (3)AR to activate simultaneously the protein kinase A and MAP kinase pathw ays. The impact of understanding these pathways and their potential role in modulating adaptive thermogenesis is discussed.