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

TitleA PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate.
Publication TypeJournal Article
Year of Publication2019
AuthorsWang, W, Ishibashi, J, Trefely, S, Shao, M, Cowan, AJ, Sakers, A, Lim, H-W, O'Connor, S, Doan, MT, Cohen, P, Baur, JA, M King, T, Veech, RL, Won, K-J, Rabinowitz, JD, Snyder, NW, Gupta, RK, Seale, P
JournalCell Metab
Volume30
Issue1
Pagination174-189.e5
Date Published2019 07 02
ISSN1932-7420
Keywords3-Hydroxybutyric Acid, Adipocytes, Adipogenesis, Adipose Tissue, Beige, Animals, Blotting, Western, DNA-Binding Proteins, Flow Cytometry, Humans, In Vitro Techniques, Male, Mass Spectrometry, Mice, Transcription Factors
Abstract

<p>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.</p>

DOI10.1016/j.cmet.2019.05.005
Alternate JournalCell Metab
PubMed ID31155495
PubMed Central IDPMC6836679
Grant ListR01 DK120982 / DK / NIDDK NIH HHS / United States
R01 DK123356 / DK / NIDDK NIH HHS / United States
R03 HD092630 / HD / NICHD NIH HHS / United States
R01 DK104789 / DK / NIDDK NIH HHS / United States
R01 DK103008 / DK / NIDDK NIH HHS / United States
R01 DK107589 / DK / NIDDK NIH HHS / United States
P30 DK019525 / DK / NIDDK NIH HHS / United States
R01 AG043483 / AG / NIA NIH HHS / United States
R01 DK098656 / DK / NIDDK NIH HHS / United States
R56 DK103008 / DK / NIDDK NIH HHS / United States