Learning New Tricks from Old Dogs: β-Adrenergic Receptors Teach New Lessons on Firing Up Adipose Tissue Metabolism

The three βAR (β-adrenergic receptor) subtypes (β1AR, β2AR, and β3AR) are members of the large family of G protein-coupled receptors, each of which is coupled to Gαs and increases in intracellular cAMP levels. In white adipose tissues, catecholamine activation of the βARs leads to the mobilization of stored fatty acids and regulates release of several adipokines, whereas in brown adipose tissue they stimulate the specialized process of adaptive nonshivering thermogenesis. Noteworthy, in most models of obesity the βAR system is dysfunctional, and its ability to stimulate lipolysis and thermogenesis are both impaired. Nevertheless, selective agonists for the β3AR, a subtype that is found predominantly in adipocytes, have been able to prevent or reverse obesity and accompanying insulin resistance in animal models. Whether this is a viable therapeutic option for human obesity is much debated with regard to the existence of brown adipocytes in humans or their ability to be recruited. Nevertheless, probing the ...