RRC ID |
2282
|
著者 |
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.
|
タイトル |
Adipose tissue-specific inactivation of the retinoblastoma protein protects against diabesity because of increased energy expenditure.
|
ジャーナル |
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.
|
巻・号 |
104(25)
|
ページ |
10703-8
|
公開日 |
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
|
引用数 |
77
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
遺伝子材料 |
AxCANCre (RDB01748)
AxCANLacZ (RDB01749). |