Initiation of myoblast to brown fat switch by a PRDM16–C/EBP-β transcriptional complex
Open accessAbstract
Brown adipose cells are specialized to dissipate chemical energy in the form of heat, as a physiological defence against cold and obesity. PRDM16 (PR domain containing 16) is a 140 kDa zinc finger protein that robustly induces brown fat determination and differentiation. Recent data suggests that brown fat cells arise in vivo from a Myf5-positive, myoblastic lineage by the action of PRDM16 (ref. 3); however, the molecular mechanisms responsible for this developmental switch is unclear. Here we show that PRDM16 forms a transcriptional complex with the active form of C/EBP-beta (also known as LAP), acting as a critical molecular unit that controls the cell fate switch from myoblastic precursors to brown fat cells. Forced expression of PRDM16 and C/EBP-beta is sufficient to induce a fully functional brown fat program in naive fibroblastic cells, including skin fibroblasts from mouse and man. Transplantation of fibroblasts expressing these two factors into mice gives rise to an ectopic fat pad with the morphological and biochemical characteristics of brown fat. Like endogenous brown fat, this synthetic brown fat tissue acts as a sink for glucose uptake, as determined by positron emission tomography with fluorodeoxyglucose. These data indicate that the PRDM16-C/EBP-beta complex initiates brown fat formation from myoblastic precursors, and may provide opportunities for the development of new therapeutics for obesity and type-2 diabetes.
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The effect of PRDM16 depends on interaction with PGC-1α/β, PPARγ and C/EBPβ, while binding to CtBP-1 and CtBP-2 suppresses expression of white fat-selective genes.
“This effect depends on the interaction of PRDM16 with PGC-1α/β, PPARγ and C/EBPβ, while binding of PRDM16 to CtBP-1 and CtBP-2 suppresses expression of white fat-selective genes 171,172.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [172]
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- Authors
- Kajimura, S., Seale, P., Kubota, K., Lunsford, E., Frangioni, J. V., Gygi, S. P., & Spiegelman, B. M.
- Affiliations
- Harvard University (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Spiegelman, Bruce M.
- Venue
- Nature
- Published
- 2009-07-29
- Volume
- 460
- Issue
- 7259
- Pages
- 1154-1158
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2754867
- OpenAlex
- W2058131133
- Cited by
- 703
- References
- 36
- Citations by year
- 2026: 21 · 2025: 27 · 2024: 24 · 2023: 28 · 2022: 33 · 2021: 37 · 2020: 44 · 2019: 45 · 2018: 49 · 2017: 51 · 2016: 38 · 2015: 60 · 2014: 51 · 2013: 61 · 2012: 54
- FWCI
- 29.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Human Genome Research Institute (HG3456, R01HG003456)
- National Institute of General Medical Sciences (GM 67945, R01GM067945)
- National Institute of Diabetes and Digestive and Kidney Diseases (K99DK087853, R01DK031405, DK-31405, K99DK081605, DK081605, R00DK081605, R37DK031405)
- National Center for Research Resources (S10RR023010)
- 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 › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- C/EBPβ, brown adipose tissue, transcriptional complex, fibroblast transplantation, glucose uptake, thermogenesis, obesity, type 2 diabetes, zinc finger proteins, cell fate conversion
- MeSH terms
- Animals, Adipose Tissue, Brown, Cell Differentiation, Cell Line, Cells, Cultured, Choristoma, DNA-Binding Proteins, Fibroblasts, Glucose, Humans, Male, Mice, Inbred C57BL, Skin, Transcription Factors, CCAAT-Enhancer-Binding Protein-beta, Myoblasts, Multiprotein Complexes, Mice
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