G protein coupled receptors (GPCRs) expressed in white and brown adipose tissue have pleiotropic effects on energy and glucose homeostasis. There are four main families of G proteins: Gi/Go, Gq, Gs, and G12. In rodents, most of the positive effects of the sympathetic nervous system on adipose tissue are attributed to Gs-coupled beta 3 adrenergic receptors located at the surface of adipocytes. Caron et al. used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), chemogenetically-engineered proteins that allow spatial and temporal control of G protein signaling in vivo. They report that Gs, but not Gi signaling in adipocytes is a potent regulator of systemic glucose homeostasis.