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A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate.

Publication ,  Journal Article
Wang, W; Ishibashi, J; Trefely, S; Shao, M; Cowan, AJ; Sakers, A; Lim, H-W; O'Connor, S; Doan, MT; Cohen, P; Baur, JA; King, MT; Veech, RL ...
Published in: Cell Metab
July 2, 2019

The precursor cells for metabolically beneficial beige adipocytes can alternatively become fibrogenic and contribute to adipose fibrosis. We found that cold exposure or β3-adrenergic agonist treatment of mice decreased the fibrogenic profile of precursor cells and stimulated beige adipocyte differentiation. This fibrogenic-to-adipogenic transition was impaired in aged animals, correlating with reduced adipocyte expression of the transcription factor PRDM16. Genetic loss of Prdm16 mimicked the effect of aging in promoting fibrosis, whereas increasing PRDM16 in aged mice decreased fibrosis and restored beige adipose development. PRDM16-expressing adipose cells secreted the metabolite β-hydroxybutyrate (BHB), which blocked precursor fibrogenesis and facilitated beige adipogenesis. BHB catabolism in precursor cells, mediated by BDH1, was required for beige fat differentiation in vivo. Finally, dietary BHB supplementation in aged animals reduced adipose fibrosis and promoted beige fat formation. Together, our results demonstrate that adipocytes secrete a metabolite signal that controls beige fat remodeling.

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Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

July 2, 2019

Volume

30

Issue

1

Start / End Page

174 / 189.e5

Location

United States

Related Subject Headings

  • Transcription Factors
  • Mice
  • Mass Spectrometry
  • Male
  • In Vitro Techniques
  • Humans
  • Flow Cytometry
  • Endocrinology & Metabolism
  • DNA-Binding Proteins
  • Blotting, Western
 

Citation

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Wang, W., Ishibashi, J., Trefely, S., Shao, M., Cowan, A. J., Sakers, A., … Seale, P. (2019). A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate. Cell Metab, 30(1), 174-189.e5. https://doi.org/10.1016/j.cmet.2019.05.005
Wang, Wenshan, Jeff Ishibashi, Sophie Trefely, Mengle Shao, Alexis J. Cowan, Alexander Sakers, Hee-Woong Lim, et al. “A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate.Cell Metab 30, no. 1 (July 2, 2019): 174-189.e5. https://doi.org/10.1016/j.cmet.2019.05.005.
Wang W, Ishibashi J, Trefely S, Shao M, Cowan AJ, Sakers A, et al. A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate. Cell Metab. 2019 Jul 2;30(1):174-189.e5.
Wang, Wenshan, et al. “A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate.Cell Metab, vol. 30, no. 1, July 2019, pp. 174-189.e5. Pubmed, doi:10.1016/j.cmet.2019.05.005.
Wang W, Ishibashi J, Trefely S, Shao M, Cowan AJ, Sakers A, Lim H-W, O’Connor S, Doan MT, Cohen P, Baur JA, King MT, Veech RL, Won K-J, Rabinowitz JD, Snyder NW, Gupta RK, Seale P. A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate. Cell Metab. 2019 Jul 2;30(1):174-189.e5.
Journal cover image

Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

July 2, 2019

Volume

30

Issue

1

Start / End Page

174 / 189.e5

Location

United States

Related Subject Headings

  • Transcription Factors
  • Mice
  • Mass Spectrometry
  • Male
  • In Vitro Techniques
  • Humans
  • Flow Cytometry
  • Endocrinology & Metabolism
  • DNA-Binding Proteins
  • Blotting, Western