| First Author | Yahagi N | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 28 | Pages | 25395-400 |
| PubMed ID | 12734185 | Mgi Jnum | J:120652 |
| Mgi Id | MGI:3707617 | Doi | 10.1074/jbc.M302364200 |
| Citation | Yahagi N, et al. (2003) p53 Activation in adipocytes of obese mice. J Biol Chem 278(28):25395-400 |
| abstractText | 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. |
