Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1α
Open accessAbstract
The Rb family, Rb, p107, and p130, play important roles in cell cycle control and cellular differentiation, and Rb has been suggested to regulate adipocyte differentiation. We report here that mice lacking p107 displayed a uniform replacement of white adipose tissue (WAT) with brown adipose tissue (BAT). Mutant WAT depots contained mutilocular adipocytes that expressed elevated levels of PGC-1alpha and UCP-1 typical of BAT. WAT from p107-/- mice contained markedly elevated numbers of adipogenic precursors that displayed downregulated expression of pRb. Consistent with the hypothesis that pRb is required for adult adipocyte differentiation, Cre-mediated deletion of Rb in adult primary preadipocytes blocked their differentiation into white adipocytes. Importantly, pRb was observed to bind the PGC-1alpha promoter and repress transcription. Therefore, p107 and pRb regulate PGC-1alpha expression to control the switch between white and brown adipocyte differentiation from a common pool of presumptive adult progenitors in fat tissue.
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Proteins of the retinoblastoma family and necdin selectively inhibit brown preadipocyte differentiation.
“Among the known inhibitors of preadipocyte-adipocyte transition, proteins of the retinoblastoma (Rb) family, and necdin, a growth repressor functionally resembling Rb, selectively inhibit brown preadipocyte differentiation 132,133,168”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [168]
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- Authors
- Scimè, A., Grenier, G., Huh, M. S., Gillespie, M. A., Bevilacqua, L., Harper, M.-E., & Rudnicki, M. A.
- Affiliations
- University of Ottawa (CA)
- Corresponding author
- Rudnicki, Michael A.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 2
- Issue
- 5
- Pages
- 283-295
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2038064796
- Cited by
- 199
- References
- 66
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 7 · 2019: 2 · 2018: 9 · 2017: 13 · 2016: 12 · 2015: 10 · 2014: 13 · 2013: 26 · 2012: 13
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- p107, Rb, p130, PGC-1α, white adipose tissue, brown adipose tissue, preadipocyte differentiation, adipogenesis, transcriptional repression, UCP1, cell cycle regulation
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Uncoupling Protein 1, Rosiglitazone, Animals, Adipose Tissue, Brown, Cell Differentiation, Cells, Cultured, Ion Channels, Mice, Inbred BALB C, Promoter Regions, Genetic, RNA, Transcription Factors, Triiodothyronine, Trans-Activators, Retinoblastoma Protein, Adipocytes, Mice, Knockout, Mitochondrial Proteins, Thiazolidinediones, Retinoblastoma-Like Protein p107, Mice, Adipose Tissue, White
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