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p53 Activation in adipocytes of obese mice.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2003 Jul 11; Vol. 278 (28), pp. 25395-400. Date of Electronic Publication: 2003 May 06. - Publication Year :
- 2003
-
Abstract
- The tumor suppressor p53 is a transcription factor that activates or represses its target genes after various genotoxic stresses. We have previously shown that sterol regulatory element-binding protein-1 (SREBP-1), a key transcriptional regulator of triglyceride synthesis, and the lipogenic enzymes under its control are markedly suppressed in adipocytes from genetically obese ob/ob mice. Here we demonstrate that p53 and its target genes are highly induced in adipocytes of ob/ob mice in a fed state, leading to the negative regulation of SREBP-1 and thereby lipogenic genes. In fact, disruption of p53 in ob/ob mice completely suppressed the p53-regulated genes to wild-type levels and partially restored expression of lipogenic enzymes. Consistently, reporter gene analysis showed that p53 overexpression suppressed the promoter activity of the SREBP-1c gene and its downstream genes. Thus, the activation of p53 might constitute a negative feedback loop against excess fat accumulation in adipocytes. In conclusion, we discovered a novel role of p53 in the pathophysiology of obesity.
- Subjects :
- Adipose Tissue metabolism
Animals
Blotting, Northern
Blotting, Western
Cell Nucleus metabolism
Crosses, Genetic
Down-Regulation
Genotype
Immunoblotting
Luciferases metabolism
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity metabolism
Plasmids metabolism
Promoter Regions, Genetic
RNA, Messenger metabolism
Sterol Regulatory Element Binding Protein 1
Transcription, Genetic
Transfection
Up-Regulation
CCAAT-Enhancer-Binding Proteins metabolism
DNA-Binding Proteins metabolism
Gene Expression Regulation
Transcription Factors
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 278
- Issue :
- 28
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12734185
- Full Text :
- https://doi.org/10.1074/jbc.M302364200