Might β3-adrenergic receptor agonists be useful in disorders of glucose homeostasis?
Jeffrey S. Flier
Abstract
When rodents are exposed to environmental cold, their brown adipose tissue (BAT) becomes activated, generating heat required for thermal homeostasis (1). The physiologic loop involves cold-induced activation of the sympathetic nervous system, which then releases noradrenaline from nerve terminals to activate 3-adrenergic receptors (3-ARs) on BAT cell membranes. Activating uncoupling protein 1 (UCP1) on the inner mitochondrial membrane then uncouples mitochondrial respiration to oxidize substrate and generate heat. A subpopulation of white adipose tissue (WAT) cells called "brite" or "beige" cells have a distinct lineage and gene expression profile and are also capable of displaying induced, uncoupled respiration through UCP1 (2). The relative contributions of BAT versus beige adipose tissues to physiology is poorly defined, and additional heterogeneity of brown adipocyte cells has recently emerged (3).