| Literature DB >> 31155495 |
Wenshan Wang1, Jeff Ishibashi1, Sophie Trefely2, Mengle Shao3, Alexis J Cowan4, Alexander Sakers1, Hee-Woong Lim5, Sean O'Connor6, Mary T Doan7, Paul Cohen6, Joseph A Baur8, M Todd King9, Richard L Veech9, Kyoung-Jae Won5, Joshua D Rabinowitz4, Nathaniel W Snyder7, Rana K Gupta3, Patrick Seale10.
Abstract
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.Entities:
Keywords: BDH1; PRDM16; UCP1; adipose fibrosis; beige fat; beta hydroxybutyrate; brown fat; fibro-adipogenic progenitor
Mesh：
Substances：
Year: 2019 PMID： 31155495 PMCID： PMC6836679 DOI： 10.1016/j.cmet.2019.05.005
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287