p53 activation in adipocytes of obese mice

Naoya Yahagi, Hitoshi Shimano*, Takashi Matsuzaka, Yuho Najima, Motohiro Sekiya, Yoshimi Nakagawa, Tomohiro Ide, Sachiko Tomita, Hiroaki Okazaki, Yoshiaki Tamura, Yoko Iizuka, Ken Ohashi, Takanari Gotoda, Ryozo Nagai, Satoshi Kimura, Shun Ishibashi, Jun Ichi Osuga, Nobuhiro Yamada

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

195 Scopus citations

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.

Original languageEnglish
Pages (from-to)25395-25400
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number28
DOIs
StatePublished - 2003/07/11

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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