@article{2564,
  author = {Wenshan Wang and Jeff Ishibashi and Sophie Trefely and Mengle Shao and Alexis Cowan and Alexander Sakers and Hee-Woong Lim and Sean O{\textquoteright}Connor and Mary Doan and Paul Cohen and Joseph Baur and Todd King and Richard Veech and Kyoung-Jae Won and Joshua Rabinowitz and Nathaniel Snyder and Rana Gupta and Patrick Seale},
  title = {A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate.},
  abstract = {<p>The precursor cells for metabolically beneficial beige\&nbsp;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\&nbsp;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.</p>
},
  year = {2019},
  journal = {Cell Metab},
  volume = {30},
  pages = {174-189.e5},
  month = {07/2019},
  issn = {1932-7420},
  doi = {10.1016/j.cmet.2019.05.005},
  language = {eng},
}