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Retinoblastoma prot...
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Hansen, Jacob B
(författare)
Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation.
- Artikel/kapitelEngelska2004
Förlag, utgivningsår, omfång ...
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2004-03-15
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Proceedings of the National Academy of Sciences,2004
Nummerbeteckningar
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LIBRIS-ID:oai:gup.ub.gu.se/52366
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https://gup.ub.gu.se/publication/52366URI
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https://doi.org/10.1073/pnas.0301964101DOI
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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.
Ämnesord och genrebeteckningar
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Adipocytes
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physiology
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Adipose Tissue
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Brown
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physiology
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Animals
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Antigens
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Polyomavirus Transforming
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physiology
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Carrier Proteins
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biosynthesis
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genetics
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Cell Differentiation
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physiology
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Cyclic AMP
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physiology
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Fibroblasts
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Ion Channels
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Membrane Proteins
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biosynthesis
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genetics
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Mice
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Mice
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Inbred C57BL
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Mitochondrial Proteins
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Rats
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Rats
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Sprague-Dawley
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Retinoblastoma Protein
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deficiency
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genetics
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physiology
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Simian virus 40
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physiology
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Jörgensen, Claus
(författare)
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Petersen, Rasmus K
(författare)
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Hallenborg, Philip
(författare)
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De Matteis, Rita
(författare)
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B?ye, Hans A
(författare)
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Petrovic, Natasa
(författare)
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Enerbäck, Sven,1958Gothenburg University,Göteborgs universitet,Institutionen för medicinsk och fysiologisk kemi,Institute of Medical Biochemistry(Swepub:gu)xenesv
(författare)
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Nedergaard, Jan
(författare)
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Cinti, Saverio
(författare)
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te Riele, Hein
(författare)
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Kristiansen, Karsten
(författare)
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Göteborgs universitetInstitutionen för medicinsk och fysiologisk kemi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences101:12, s. 4112-70027-8424
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Ingår i:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences101:12, s. 4112-71091-6490
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Hansen, Jacob B
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Jörgensen, Claus
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Petersen, Rasmus ...
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Hallenborg, Phil ...
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De Matteis, Rita
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B?ye, Hans A
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visa fler...
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Petrovic, Natasa
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Enerbäck, Sven, ...
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Nedergaard, Jan
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Cinti, Saverio
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te Riele, Hein
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Kristiansen, Kar ...
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Göteborgs universitet