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

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

195 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)25395-25400
ページ数6
ジャーナルJournal of Biological Chemistry
278
28
DOI
出版ステータス出版済み - 2003/07/11

ASJC Scopus 主題領域

  • 生化学
  • 分子生物学
  • 細胞生物学

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