The β-adrenergic receptors and the control of adipose tissue metabolism and thermogenesis
The β-adrenergic receptors (βARs) are members of the large family of G protein-coupled receptors. There are three βAR subtypes (β1AR, β2AR β3AR), each of which is coupled to Gαs and the stimulation of intracellular cAMP levels. While β1AR and β2AR are broadly expressed throughout tissues of the body, β3AR is found predominantly in adipocytes. Stimulation of the βARs leads to lipolysis in white adipocytes and nonshivering thermogenesis in brown fat. However, in essentially all animal models of obesity, the βAR system is dysfunctional and the ability to stimulate lipolysis and thermogenesis is impaired. Nevertheless, we and others have shown that selective β3AR agonists are able to prevent or reverse obesity and the loss of βAR expression and to stimulate thermogenesis. This chapter will review the current understanding of the role of the sympathetic nervous system and the adipocyte βARs in models of obesity; the physiologic impact of changes in βAR expression on body composition and thermogenesis; and the regulation and unique properties of βAR subtypes in brown and white adipocytes. The latter includes our recent discovery of novel signal transduction mechanisms utilized by β3AR 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.
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