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Recent Progress in Hormone Research 56:309-328 (2001)
© 2001 The Endocrine Society

The ß-Adrenergic Receptors and the Control of Adipose Tissue Metabolism and Thermogenesis

Sheila Collins*,{dagger} and Richard S. Surwit{dagger}

* Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710
{dagger} Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710

ABSTRACT

The ß-adrenergic receptors (ßARs) are members of the large family of G protein-coupled receptors. There are three ßAR subtypes (ß1AR, ß2AR, ß3AR), each of which is coupled to G{alpha}s and the stimulation of intracellular cAMP levels. While ß1AR and ß2AR are broadly expressed throughout tissues of the body, ß3AR is found predominantly in adipocytes. Stimulation of the ßARs leads to lipolysis in white adipocytes and nonshivering thermogenesis in brown fat. However, in essentially all animal models of obesity, the ßAR system is dysfunctional and the ability to stimulate lipolysis and thermogenesis is impaired. Nevertheless, we and others have shown that selective ß3AR agonists are able to prevent or reverse obesity and the loss ofßAR expression and to stimulate thermogenesis. This chapter will review the current understanding of the role of the sympathetic nervous system and the adipocyte ßARs in models of obesity; the physiologic impact of changes in ßAR expression on body composition and thermogenesis; and the regulation and unique properties of ßAR subtypes in brown and white adipocytes. The latter includes our recent discovery of novel signal transduction mechanisms utilized by ß3AR 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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