Transcriptional Control of Brown Fat Determination by PRDM16
Open accessAbstract
Brown fat cells are specialized to dissipate energy and can counteract obesity; however, the transcriptional basis of their determination is largely unknown. We show here that the zinc-finger protein PRDM16 is highly enriched in brown fat cells compared to white fat cells. When expressed in white fat cell progenitors, PRDM16 activates a robust brown fat phenotype including induction of PGC-1alpha, UCP1, and type 2 deiodinase (Dio2) expression and a remarkable increase in uncoupled respiration. Transgenic expression of PRDM16 at physiological levels in white fat depots stimulates the formation of brown fat cells. Depletion of PRDM16 through shRNA expression in brown fat cells causes a near total loss of the brown characteristics. PRDM16 activates brown fat cell identity at least in part by simultaneously activating PGC-1alpha and PGC-1beta through direct protein binding. These data indicate that PRDM16 can control the determination of brown fat fate.
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PRDM16 drives differentiation of white preadipocytes or myoblasts into functional brown adipocytes.
“The zinc-finger containing protein, PRDM16, which is expressed at higher levels in brown compared with white adipocytes 131, has been shown to drive differentiation of white preadipocytes or myoblasts into functional brown adipocytes.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [131]
PRDM16 is expressed at higher levels in brown compared with white adipocytes.
“The zinc-finger containing protein, PRDM16, which is expressed at higher levels in brown compared with white adipocytes 131, has been shown to drive differentiation of white preadipocytes or myoblasts into functional brown adipocytes.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [131]
The genetic program leading to brown adipose tissue development, and potentially to the high abundance of mitochondria, is initiated by the zinc-finger protein PRDM16.
“The genetic program leading to brown adipose tissue development, and potentially to the high abundance of mitochondria, is initiated by the zinc-finger protein PRDM16 (202)(203)(204).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [202]
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- Authors
- Seale, P., Kajimura, S., Yang, W., Chin, S., Rohas, L. M., Uldry, M., Tavernier, G., Langin, D., & Spiegelman, B. M.
- Affiliations
- Harvard University (US)
- Université Toulouse III - Paul Sabatier (FR)
- Corresponding author
- Spiegelman, Bruce M.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-07
- Volume
- 6
- Issue
- 1
- Pages
- 38-54
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2564846
- OpenAlex
- W1992326632
- Cited by
- 1,174
- References
- 88
- Citations by year
- 2026: 37 · 2025: 63 · 2024: 66 · 2023: 66 · 2022: 52 · 2021: 78 · 2020: 86 · 2019: 65 · 2018: 80 · 2017: 76 · 2016: 63 · 2015: 70 · 2014: 68 · 2013: 81 · 2012: 58
- FWCI
- 27.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- American Heart Association
- Genome Canada
- European Commission
- Agence Nationale de la Recherche
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK031405, DK31405-24, R37DK031405)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- PRDM16, brown adipose tissue, transcriptional regulation, PGC-1α, PGC-1β, UCP1, type 2 deiodinase, uncoupled respiration, obesity
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Uncoupling Protein 1, Iodothyronine Deiodinase Type II, Animals, Adipose Tissue, Brown, Cell Differentiation, Cells, Cultured, Chlorocebus aethiops, DNA-Binding Proteins, Fibroblasts, Gene Expression Regulation, Iodide Peroxidase, Ion Channels, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Oxygen Consumption, Phenotype, Transcription Factors, Transcription, Genetic, Blotting, Western, Trans-Activators, Adipocytes, Genes, Reporter, Mice, Knockout, Cell Respiration, COS Cells, Reverse Transcriptase Polymerase Chain Reaction, Mitochondrial Proteins, Electrophoretic Mobility Shift Assay, 3T3-L1 Cells, Mice, Adipose Tissue, White, Adipocytes, Brown, Adipocytes, White
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