Journal article
A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate
Cell metabolism, v 30(1), pp 174-189
02 Jul 2019
PMID: 31155495
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The precursor cells for metabolically beneficial beige adipocytes can alternatively become fibrogenic and contribute to adipose fibrosis. We found that cold exposure or beta 3-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 beta-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.
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Details
- Title
- A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate
- Creators
- Wenshan Wang - University of PennsylvaniaJeff Ishibashi - University of PennsylvaniaSophie Trefely - Drexel UniversityMengle Shao - The University of Texas Southwestern Medical CenterAlexis J. Cowan - Princeton UniversityAlexander Sakers - University of PennsylvaniaHee-Woong Lim - University of PennsylvaniaSean O'Connor - Rockefeller UniversityMary T. Doan - Drexel UniversityPaul Cohen - Rockefeller UniversityJoseph A. Baur - University of PennsylvaniaM. Todd King - Laboratory of Metabolic Control, NIH/NIAAA, Rockville, MD, USA.Richard L. Veech - Laboratory of Metabolic Control, NIH/NIAAA, Rockville, MD, USA.Kyoung-Jae Won - University of PennsylvaniaJoshua D. Rabinowitz - Princeton UniversityNathaniel W. Snyder - Drexel UniversityRana K. Gupta - The University of Texas Southwestern Medical CenterPatrick Seale - University of Pennsylvania
- Publication Details
- Cell metabolism, v 30(1), pp 174-189
- Publisher
- Elsevier
- Number of pages
- 21
- Grant note
- DK103008 / NIH/NIDDK; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) 1-18-PDF-144 / American Diabetes Association (ADA); American Diabetes Association 1-16-IBS-269 / ADA; American Diabetes Association ZIAAA000110 / NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) DK098656; AG043483 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R03HD092630 / NIH/NICHD; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) 15POST25700059 / American Heart Association (AHA) fellowship; American Heart Association R01DK103008 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000473420800019
- Scopus ID
- 2-s2.0-85067899280
- Other Identifier
- 991019167868504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology
- Endocrinology & Metabolism