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

  1. Yuwei Jiang
  2. Daniel C Berry  Is a corresponding author
  3. Jon Graff  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States

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.

Article and author information

Author details

  1. Yuwei Jiang

    Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    No competing interests declared.
  2. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5200-1182
  3. 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

© 2017, Jiang et al.

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.

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  1. Yuwei Jiang
  2. Daniel C Berry
  3. Jon Graff
(2017)
Distinct cellular and molecular mechanisms for β3 adrenergic receptor induced beige adipocyte formation
eLife 6:e30329.
https://doi.org/10.7554/eLife.30329

Share this article

https://doi.org/10.7554/eLife.30329

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