Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr 1;105(4):dgz298.
doi: 10.1210/clinem/dgz298.

Beta-1 and Not Beta-3 Adrenergic Receptors May Be the Primary Regulator of Human Brown Adipocyte Metabolism

Mette Ji Riis-Vestergaard  1   2   3 , Bjørn Richelsen  1   2   3 , Jens Meldgaard Bruun  2   3 , Wei Li  4 , Jacob B Hansen  4 , Steen Bønløkke Pedersen  1   2   3
Affiliations

Beta-1 and Not Beta-3 Adrenergic Receptors May Be the Primary Regulator of Human Brown Adipocyte Metabolism

Mette Ji Riis-Vestergaard et al. J Clin Endocrinol Metab. .

Abstract

Purpose: Brown adipose tissue (BAT) activation in humans has gained interest as a potential target for treatment of obesity and insulin resistance. In rodents, BAT is primarily induced through beta-3 adrenergic receptor (ADRB3) stimulation, whereas the primary beta adrenergic receptors (ADRBs) involved in human BAT activation are debated. We evaluated the importance of different ADRB subtypes for uncoupling protein 1 (UCP1) induction in human brown adipocytes.

Methods: A human BAT cell model (TERT-hBA) was investigated for subtype-specific ADRB agonists and receptor knockdown on UCP1 mRNA levels and lipolysis (glycerol release). In addition, fresh human BAT biopsies and TERT-hBA were evaluated for expression of ADRB1, ADRB2, and ADRB3 using RT-qPCR.

Results: The predominant ADRB subtype in TERT-hBA adipocytes and BAT biopsies was ADRB1. In TERT-hBA, UCP1 mRNA expression was stimulated 11.0-fold by dibutyryl cAMP (dbcAMP), 8.0-fold to 8.4-fold by isoproterenol (ISO; a pan-ADRB agonist), and 6.1-fold to 12.7-fold by dobutamine (ADRB1 agonist), whereas neither procaterol (ADRB2 agonist), CL314.432, or Mirabegron (ADRB3 agonists) affected UCP1. Similarly, dbcAMP, ISO, and dobutamine stimulated glycerol release, whereas lipolysis was unaffected by ADRB2 and ADRB3 agonists. Selective knockdown of ADRB1 significantly attenuated ISO-induced UCP1 expression.

Conclusion: The adrenergic stimulation of UCP1 and lipolysis may mainly be mediated through ADRB1. Moreover, ADRB1 is the predominant ADRB in both TERT-hBA and human BAT biopsies. Thus, UCP1 expression in human BAT may, unlike in rodents, primarily be regulated by ADRB1. These findings may have implications for ADRB agonists as future therapeutic compounds for human BAT activation.

Keywords: UCP1; beta adrenergic regulation; beta-3 adrenergic receptor; brown adipocytes; human.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

Substances