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Göteborgs universitets publikationer

Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation.

Författare och institution:
Jacob B Hansen (-); Claus Jörgensen (-); Rasmus K Petersen (-); Philip Hallenborg (-); Rita De Matteis (-); Hans A B?ye (-); Natasa Petrovic (-); Sven Enerbäck (Institutionen för medicinsk och fysiologisk kemi); Jan Nedergaard (-); Saverio Cinti (-); Hein te Riele (-); Karsten Kristiansen (-)
Publicerad i:
Proceedings of the National Academy of Sciences of the United States of America, 101 ( 12 ) s. 4112-7
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
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
Postens nummer:
Posten skapad:
2007-10-09 14:07
Posten ändrad:
2011-01-20 09:59

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