Distinct cellular and molecular mechanisms for β3 adrenergic receptor induced beige adipocyte formation

Abstract
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Abstract

Beige/brite adipocytes are induced within white adipose tissues (WAT) and, when activated, consume glucose and fatty acids to produce heat. Classically, two stimuli have been used to trigger a beiging response: cold temperatures and β3-adrenergic receptor (Adrb3) agonists. These two beiging triggers have been used interchangeably but whether these two stimuli may induce beiging differently at cellular and molecular levels remains unclear. Here we found that cold-induced beige adipocyte formation requires Adrb1, not Adrb3, activation. Adrb1 activation stimulates WAT resident perivascular (Acta2+) cells to form cold-induced beige adipocytes. In contrast, Adrb3 activation stimulates mature white adipocytes to convert into beige adipocytes. Necessity tests, using mature adipocyte specific Prdm16 deletion strategies, demonstrated that adipocytes are a required and are a predominant source to generate Adrb3-induced, but not cold-induced, beige adipocytes. Collectively, we identify that cold temperatures and Adrb3 agonists activate distinct cellular populations that express different β-adrenergic receptors to induce beige adipogenesis.

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Author details

Yuwei Jiang

Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States

Competing interests
No competing interests declared.
Daniel C Berry

Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States

For correspondence
dcb37@cornell.edu

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-5200-1182
Jon Graff

Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States

For correspondence
jon.graff@utsouthwestern.edu

Competing interests
Jon Graff, is a co-founder and shareholder of Reata Pharmaceuticals. Reata Pharmaceuticals has no financial interest in this study.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K01 DK109027)

Daniel C Berry

National Institute of Diabetes and Digestive and Kidney Diseases (K01 DK111771)

Yuwei Jiang

National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK088220)

Jon Graff

National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK064261)

Jon Graff

National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK066556)

Jon Graff

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals were maintained under the approved protocols and ethical guidelines of the UT Southwestern Medical Center Animal Care and Use Committee under the protocol number 2016--101336.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.