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β3 Adrenergic Receptors as a Therapeutic Target for Obesity

  • Chapter
Obesity: Pathology and Therapy

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 149))

  • 305 Accesses

Abstract

The physiological actions of catecholamines are mediated via a- and β-adrenergic receptors (AR). Activation of adipocyte βAR results in lipid mobilization and release from white adipose tissue, and oxidation of fatty acids in brown fat. The net effect of adipocyte βAR activation is the reduction of triglyceride stores in white fat with a concomitant increase in thermogenesis and thermogenic capacity of brown fat. Because of the potential significance of adipocyte βAR in overall energy balance, much attention has been devoted to their characterization. Pioneering work by Harms et al. (1974) suggested the existence of βAR with atypically low affinity for standard βAR antagonists in adipocytes; however the notion of an “atypical” adipocyte βAR was not widely accepted at the time owing to the lack of selective pharmacological agents. Thus, available radioligands failed to detect these atypical receptors and no agonists were available that would selectively activate them (Bahouth and Malbon 1988). This state of affairs changed dramatically nearly 15 years ago when researchers at Beecham Pharmaceuticals identified novel compounds that potently induced thermogenesis in rats via interactions with an atypical βAR (Arch et al. 1984). These agents placed the concept of an atypical adipocyte βAR on solid pharmacological ground, and ultimately provided the impetus for the molecular cloning of the β3AR. Perhaps more significantly, the agents discovered by Beecham were found to be highly effective in rodent models of obesity and adult-onset diabetes, holding out the promise that the “atypical” adipocyte β3AR would be an important therapeutic target for the treatment of human disease.

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  1. J. G. Granneman
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  1. Department of Clinical Research, Parke-Davis Pharmaceutical Research, Division of Warner Lambert Company, 2800 Plymouth Road, Ann Arbor, MI, 48105, USA

    Dean H. Lockwood M.D. (Vice President) (Vice President)

  2. Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Division of Warner Lambert Company, 2800 Plymouth Road, Ann Arbor, MI, 48105, USA

    Thomas C. Heffner Ph.D. (Sr. Director) (Sr. Director)

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Granneman, J.G. (2000). β3 Adrenergic Receptors as a Therapeutic Target for Obesity. In: Lockwood, D.H., Heffner, T.C. (eds) Obesity: Pathology and Therapy. Handbook of Experimental Pharmacology, vol 149. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59651-3_14

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