AMP-activated protein kinase inhibits the glucose-activated expression of fatty acid synthase gene in rat hepatocytes

被引:201
作者
Foretz, M
Carling, D
Guichard, C
Ferré, P
Foufelle, F
机构
[1] Hammersmith Hosp, Royal Postgrad Med Sch, Mol Med Grp, MRC,Clin Sci Ctr, London W12 0NN, England
[2] Ctr Biomed Cordeliers, INSERM, U465, F-75270 Paris 06, France
关键词
D O I
10.1074/jbc.273.24.14767
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although it is now clearly established that a number of genes involved in glucose and lipid metabolism are up-regulated by high glucose concentrations in both liver and adipose tissue, the signaling pathway arising from glucose to the transcriptional machinery is still poorly understood. We have analyzed the regulation of fatty acid synthase gene expression by glucose in cultured rat hepatocytes. Glucose (25 mM) induces an activation of the transcription of the fatty acid synthase gene, and this effect is markedly reduced by incubation of the cells with okadaic acid, an inhibitor of protein phosphatases 1 and 2A. A similar reduction in glucose-activated fatty acid synthase gene expression is obtained by incubation with 5-amino-imidazolecarboxamide riboside, a cell-permeable activator of the AMP-activated protein kinase. Taken together, these results indicate that the glucose-induced expression of the fatty acid synthase gene involves a phosphorylation/dephosphorylation mechanism and suggest that the AMP-activated protein kinase plays an important role in this process. This is the first evidence that implicates the AMP-activated protein kinase in the regulation of gene expression. AMP-activated protein kinase is the mammalian analog of SNF1, a kinase involved in yeast in the transcriptional regulation of genes by glucose.
引用
收藏
页码:14767 / 14771
页数:5
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