TY - JOUR
T1 - β3-Adrenergic receptors regulate human brown/beige adipocyte lipolysis and thermogenesis
AU - Cero, Cheryl
AU - Lea, Hannah J.
AU - Zhu, Kenneth Y.
AU - Shamsi, Farnaz
AU - Tseng, Yu Hua
AU - Cypess, Aaron M.
N1 - Publisher Copyright:
© 2021 American Society for Clinical Investigation. All rights reserved.
PY - 2021/6/8
Y1 - 2021/6/8
N2 - β3-Adrenergic receptors (β3-ARs) are the predominant regulators of rodent brown adipose tissue (BAT) thermogenesis. However, in humans, the physiological relevance of BAT and β3-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 β3-AR plays a critical role in regulating lipolysis, glycolysis, and thermogenesis. Silencing of the β3-AR compromised genes essential for thermogenesis, fatty acid metabolism, and mitochondrial mass. Functionally, reduction of β3-AR lowered agonist-mediated increases in intracellular cAMP, lipolysis, and lipolysis-activated, uncoupling protein 1-mediated thermogenic capacity. Furthermore, mirabegron, a selective human β3-AR agonist, stimulated BAT lipolysis and thermogenesis, and both processes were lost after silencing β3-AR expression. This study highlights that β3-ARs in human brown/beige adipocytes are required to maintain multiple components of the lipolytic and thermogenic cellular machinery and that β3-AR agonists could be used to achieve metabolic benefit in humans.
AB - β3-Adrenergic receptors (β3-ARs) are the predominant regulators of rodent brown adipose tissue (BAT) thermogenesis. However, in humans, the physiological relevance of BAT and β3-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 β3-AR plays a critical role in regulating lipolysis, glycolysis, and thermogenesis. Silencing of the β3-AR compromised genes essential for thermogenesis, fatty acid metabolism, and mitochondrial mass. Functionally, reduction of β3-AR lowered agonist-mediated increases in intracellular cAMP, lipolysis, and lipolysis-activated, uncoupling protein 1-mediated thermogenic capacity. Furthermore, mirabegron, a selective human β3-AR agonist, stimulated BAT lipolysis and thermogenesis, and both processes were lost after silencing β3-AR expression. This study highlights that β3-ARs in human brown/beige adipocytes are required to maintain multiple components of the lipolytic and thermogenic cellular machinery and that β3-AR agonists could be used to achieve metabolic benefit in humans.
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U2 - 10.1172/jci.insight.139160
DO - 10.1172/jci.insight.139160
M3 - Article
C2 - 34100382
AN - SCOPUS:85107423653
SN - 2379-3708
VL - 6
JO - JCI Insight
JF - JCI Insight
IS - 11
M1 - e139160
ER -