The β-adrenergic receptors and the control of adipose tissue metabolism and thermogenesis

The beta -adrenergic receptors (beta ARs) are members of the large family of 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 stimulation of intracellular cAMP levels. While beta (1)AR and beta (2)AR are broadly expressed throughout tissues of the body, beta (3)AR is found predominantly in adipocytes. Stimulation of the beta ARs leads to lipolysis in white adipocytes and nonshivering thermogenesis in brown fat. However, in essentially all animal models of obesity, the beta AR system is dysfunctional and the ability to stimulate lipolysis and thermogenesis is impaired. Nevertheless, 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 stimulate thermogenesis. This chapter will review the current understanding of the role of the sympathetic nervous system and the adipocyte beta ARs in models of obesity; the physiologic impact of changes in beta AR expression on body composition and thermogenesis; and the regulation and unique properties of beta AR subtypes in brown and white adipocytes, The latter includes our recent discovery of novel signal transduction mechanisms utilized by beta (3)AR to activate simultaneously the protein kinase A and MAP kinase pathways. The impact of understanding these pathways and their potential role in modulating adaptive thermogenesis is discussed.