ß3-Adrenergic receptors regulate human brown/beige adipocyte lipolysis and thermogenesis.

ABSTRACT

ß3-Adrenergic receptors (ß3-ARs) are the predominant regulators of rodent brown adipose tissue (BAT) thermogenesis. However, in humans, the physiological relevance of BAT and ß3-AR remains controversial. Herein, using primary human adipocytes from supraclavicular neck fat and immortalized brown/beige adipocytes from deep neck fat from 2 subjects, we demonstrate that the ß3-AR plays a critical role in regulating lipolysis, glycolysis, and thermogenesis. Silencing of the ß3-AR compromised genes essential for thermogenesis, fatty acid metabolism, and mitochondrial mass. Functionally, reduction of ß3-AR lowered agonist-mediated increases in intracellular cAMP, lipolysis, and lipolysis-activated, uncoupling protein 1-mediated thermogenic capacity. Furthermore, mirabegron, a selective human ß3-AR agonist, stimulated BAT lipolysis and thermogenesis, and both processes were lost after silencing ß3-AR expression. This study highlights that ß3-ARs in human brown/beige adipocytes are required to maintain multiple components of the lipolytic and thermogenic cellular machinery and that ß3-AR agonists could be used to achieve metabolic benefit in humans.