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β3-Adrenergic receptors regulate human brown/beige adipocyte lipolysis and thermogenesis

Cero, Cheryl, Lea, Hannah J., Zhu, Kenneth Y., Shamsi, Farnaz, Tseng, Yu-Hua, Cypess, Aaron M.·2021·JCI Insight
DOI 10.1172/jci.insight.139160
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Abstract

β 3 -Adrenergic receptors (β 3 -ARs) are the predominant regulators of rodent brown adipose tissue (BAT) thermogenesis. However, in humans, the physiological relevance of BAT and β 3 -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 β 3 -AR plays a critical role in regulating lipolysis, glycolysis, and thermogenesis. Silencing of the β 3 -AR compromised genes essential for thermogenesis, fatty acid metabolism, and mitochondrial mass. Functionally, reduction of β 3 -AR lowered agonist-mediated increases in intracellular cAMP, lipolysis, and lipolysis-activated, uncoupling protein 1–mediated thermogenic capacity. Furthermore, mirabegron, a selective human β 3 -AR agonist, stimulated BAT lipolysis and thermogenesis, and both processes were lost after silencing β 3 -AR expression. This study highlights that β 3 -ARs in human brown/beige adipocytes are required to maintain multiple components of the lipolytic and thermogenic cellular machinery and that β 3 -AR agonists could be used to achieve metabolic benefit in humans.

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Metadata

Authors
Cero, C., Lea, H. J., Zhu, K. Y., Shamsi, F., Tseng, Y.-H., & Cypess, A. M.
Venue
JCI Insight
Publisher
American Society for Clinical Investigation
Published
2021-06-08
Volume
6
Issue
11
ISSN
2379-3708
DOI
10.1172/jci.insight.139160
Cited by
250
References
12
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
NIDDK, NIH (DK-075112,DK-075115,, DK-075116)

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