TY - JOUR
T1 - p53 activation in adipocytes of obese mice
AU - Yahagi, Naoya
AU - Shimano, Hitoshi
AU - Matsuzaka, Takashi
AU - Najima, Yuho
AU - Sekiya, Motohiro
AU - Nakagawa, Yoshimi
AU - Ide, Tomohiro
AU - Tomita, Sachiko
AU - Okazaki, Hiroaki
AU - Tamura, Yoshiaki
AU - Iizuka, Yoko
AU - Ohashi, Ken
AU - Gotoda, Takanari
AU - Nagai, Ryozo
AU - Kimura, Satoshi
AU - Ishibashi, Shun
AU - Osuga, Jun Ichi
AU - Yamada, Nobuhiro
PY - 2003/7/11
Y1 - 2003/7/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0038491561&partnerID=8YFLogxK
U2 - 10.1074/jbc.M302364200
DO - 10.1074/jbc.M302364200
M3 - 学術論文
C2 - 12734185
AN - SCOPUS:0038491561
SN - 0021-9258
VL - 278
SP - 25395
EP - 25400
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 28
ER -