RRC ID 2282
Author Dali-Youcef N, Mataki C, Coste A, Messaddeq N, Giroud S, Blanc S, Koehl C, Champy MF, Chambon P, Fajas L, Metzger D, Schoonjans K, Auwerx J.
Title Adipose tissue-specific inactivation of the retinoblastoma protein protects against diabesity because of increased energy expenditure.
Journal Proc Natl Acad Sci U S A
Abstract The role of the tumor suppressor retinoblastoma protein (pRb) has been firmly established in the control of cell cycle, apoptosis, and differentiation. Recently, it was demonstrated that lack of pRb promotes a switch from white to brown adipocyte differentiation in vitro. We used the Cre-Lox system to specifically inactivate pRb in adult adipose tissue. Under a high-fat diet, pRb-deficient (pRb(ad-/-)) mice failed to gain weight because of increased energy expenditure. This protection against weight gain was caused by the activation of mitochondrial activity in white and brown fat as evidenced by histologic, electron microscopic, and gene expression studies. Moreover, pRb(-/-) mouse embryonic fibroblasts displayed higher proliferation and apoptosis rates than pRb(+/+) mouse embryonic fibroblasts, which could contribute to the altered white adipose tissue morphology. Taken together, our data support a direct role of pRb in adipocyte cell fate determination in vivo and suggest that pRb could serve as a potential therapeutic target to trigger mitochondrial activation in white adipose tissue and brown adipose tissue, favoring an increase in energy expenditure and subsequent weight loss.
Volume 104(25)
Pages 10703-8
Published 2007-6-19
DOI 10.1073/pnas.0611568104
PII 0611568104
PMID 17556545
PMC PMC1965576
MeSH Adipose Tissue, Brown / physiology* Adipose Tissue, Brown / ultrastructure Adipose Tissue, White / physiology* Adipose Tissue, White / ultrastructure Animals Apoptosis Body Weight Cell Proliferation Cells, Cultured DNA, Mitochondrial / analysis Dietary Fats / administration & dosage Energy Metabolism* Fibroblasts / physiology Gene Expression Immunohistochemistry Mice Mice, Inbred C57BL Obesity / prevention & control* Retinoblastoma Protein / genetics Retinoblastoma Protein / physiology* Time Factors
IF 9.412
Times Cited 77
DNA material AxCANCre (RDB01748) AxCANLacZ (RDB01749).