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Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation.
- Hansen, Jacob B (författare)
- Jörgensen, Claus (författare)
- Petersen, Rasmus K (författare)
- visa fler...
- Hallenborg, Philip (författare)
- De Matteis, Rita (författare)
- B?ye, Hans A (författare)
- Petrovic, Natasa (författare)
- Nedergaard, Jan (författare)
- Cinti, Saverio (författare)
- te Riele, Hein (författare)
- Kristiansen, Karsten (författare)
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- (creator_code:org_t)
- 2004-03-15
- 2004
- Engelska.
- Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 101:12, s. 4112-7
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Adipocyte precursor cells give raise to two major cell populations with different physiological roles: white and brown adipocytes. Here we demonstrate that the retinoblastoma protein (pRB) regulates white vs. brown adipocyte differentiation. Functional inactivation of pRB in wild-type mouse embryo fibroblasts (MEFs) and white preadipocytes by expression of simian virus 40 large T antigen results in the expression of the brown fat-specific uncoupling protein 1 (UCP-1) in the adipose state. Retinoblastoma gene-deficient (Rb-/-) MEFs and stem cells, but not the corresponding wild-type cells, differentiate into adipocytes with a gene expression pattern and mitochondria content resembling brown adipose tissue. pRB-deficient MEFs exhibit an increased expression of the Forkhead transcription factor Foxc2 and its target gene cAMP-dependent protein kinase regulatory subunit RIalpha, resulting in increased cAMP sensitivity. Suppression of cAMP-dependent protein kinase activity in Rb(-/-)MEFs blocked the brown adipocyte-like gene expression pattern without affecting differentiation per se. Immunohistochemical studies revealed that pRB is present in the nuclei of white but not brown adipocyte precursor cells at a developmental stage where both cell types begin to accumulate lipid and brown adipocytes express UCP-1. Furthermore, pRB rapidly undergoes phosphorylation upon cold-induced neodifferentiation and up-regulation of UCP-1 expression in brown adipose tissue. Finally, down-regulation of pRB expression accompanies transdifferentiation of white into brown adipocytes in response to beta3-adrenergic receptor agonist treatment. We propose that pRB acts as a molecular switch determining white vs. brown adipogenesis, suggesting a previously uncharacterized function of this key cell cycle regulator in adipocyte lineage commitment and differentiation.
Nyckelord
- Adipocytes
- physiology
- Adipose Tissue
- Brown
- physiology
- Animals
- Antigens
- Polyomavirus Transforming
- physiology
- Carrier Proteins
- biosynthesis
- genetics
- Cell Differentiation
- physiology
- Cyclic AMP
- physiology
- Fibroblasts
- Ion Channels
- Membrane Proteins
- biosynthesis
- genetics
- Mice
- Mice
- Inbred C57BL
- Mitochondrial Proteins
- Rats
- Rats
- Sprague-Dawley
- Retinoblastoma Protein
- deficiency
- genetics
- physiology
- Simian virus 40
- physiology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Hansen, Jacob B
- Jörgensen, Claus
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- De Matteis, Rita
- B?ye, Hans A
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- Nedergaard, Jan
- Cinti, Saverio
- te Riele, Hein
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