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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • July 2, 2019

Published In

Volume / Issue

  • 30 / 1

Start / End Page

  • 174 - 189.e5

PubMed ID

  • 31155495

Pubmed Central ID

  • PMC6836679

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2019.05.005

Language

  • eng

Conference Location

  • United States