Sterol-regulatory-element-binding protein 1c mediates the effect of insulin on the expression of Cidea in mouse hepatocytes.
Members of the Cide [cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector] gene family have been reported to be associated with lipid metabolism. In the present study, we show that Cidea mRNA levels are markedly reduced by fasting and are restored upon refeeding in mouse livers. To elucidate the molecular mechanism, the promoter region of the mouse Cidea gene was analysed and a putative SRE (sterol-regulatory element) was identified. Studies using luciferase reporter constructs together with electrophoretic mobility-shift assays and chromatin immunoprecipitation confirmed the binding of SREBP-1c (SRE-binding protein 1c) to the putative SRE. Furthermore, adenovirus-mediated overexpression of SREBP-1c led to a dramatic increase in Cidea mRNA. In contrast with the induction of Cidea expression by insulin and TO901317 in wild-type mouse hepatocytes, the stimulatory effects were lost in hepatocytes prepared from SREBP-1c-null mice. Adenovirus-mediated overexpression of Cidea in hepatocytes promoted lipid accumulation and triacylglycerol (triglyceride) storage; however, knockdown of Cidea compromised the ability of SREBP-1c to stimulate lipid accumulation. Taken together, these results suggest that SREBP-1c directly mediates the effect of insulin on Cidea in hepatocytes and that Cidea, at least in part, mediates SREBP-1c-dependent lipid accumulation.
Wang
Rui
R
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Kong
Xingxing
X
Cui
Anfang
A
Liu
Xiaojun
X
Xiang
Ruolan
R
Yang
Yanli
Y
Guan
Youfei
Y
Fang
Fude
F
Chang
Yongsheng
Y
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; D007328:Insulin; D051780:Sterol Regulatory Element Binding Protein 1