A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate
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A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate. / Wang, Wenshan; Ishibashi, Jeff; Trefely, Sophie; Shao, Mengle; Cowan, Alexis J.; Sakers, Alexander; Lim, Hee Woong; O'Connor, Sean; Doan, Mary T.; Cohen, Paul; Baur, Joseph A.; King, M. Todd; Veech, Richard L.; Won, Kyoung Jae; Rabinowitz, Joshua D.; Snyder, Nathaniel W.; Gupta, Rana K.; Seale, Patrick.
I: Cell Metabolism, Bind 30, Nr. 1, 02.07.2019, s. 174-189.e5.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate
AU - Wang, Wenshan
AU - Ishibashi, Jeff
AU - Trefely, Sophie
AU - Shao, Mengle
AU - Cowan, Alexis J.
AU - Sakers, Alexander
AU - Lim, Hee Woong
AU - O'Connor, Sean
AU - Doan, Mary T.
AU - Cohen, Paul
AU - Baur, Joseph A.
AU - King, M. Todd
AU - Veech, Richard L.
AU - Won, Kyoung Jae
AU - Rabinowitz, Joshua D.
AU - Snyder, Nathaniel W.
AU - Gupta, Rana K.
AU - Seale, Patrick
PY - 2019/7/2
Y1 - 2019/7/2
N2 - 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.
AB - 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.
KW - adipose fibrosis
KW - BDH1
KW - beige fat
KW - beta hydroxybutyrate
KW - brown fat
KW - fibro-adipogenic progenitor
KW - PRDM16
KW - UCP1
UR - http://www.scopus.com/inward/record.url?scp=85067899280&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2019.05.005
DO - 10.1016/j.cmet.2019.05.005
M3 - Journal article
C2 - 31155495
AN - SCOPUS:85067899280
VL - 30
SP - 174-189.e5
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 1
ER -
ID: 237099030