CLOCK/BMAL1 is involved in lipid metabolism via transactivation of the peroxisome proliferator-activated receptor (PPAR) response element

被引：105

作者：

Inoue, I

Shinoda, Y

Ikeda, M

Hayashi, K

Kanazawa, K

Nomura, M

Matsunaga, T

Xu, HY

Kawai, S

Awata, T

Komoda, T

Katayama, S

机构：

[1] Saitama Med Sch, Res Ctr Genom Med, Dept Med 4, Moroyama, Saitama 3500495, Japan

[2] Saitama Med Sch, Res Ctr Genom Med, Dept Biochem, Moroyama, Saitama 3500495, Japan

[3] Saitama Med Sch, Res Ctr Genom Med, Dept Physiol, Moroyama, Saitama 3500495, Japan

[4] Saitama Med Sch, Res Ctr Genom Med, Mol Clock Project, Moroyama, Saitama 3500495, Japan

来源：

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS | 2005年 / 12卷 / 03期

关键词：

CLOCK; BMAL1; PPAR alpha; acyl-CoA oxidase; HMG-CoA synthase; cellular retinol binding protein II (CRBP II);

D O I：

10.5551/jat.12.169

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Lipid absorption and metabolism are regulated by feeding and by the circadian system. It has been suggested that the expression of enzymes involved in lipid metabolism is directly controlled by the clock system. This study was designed to examine whether or not the CLOCK/BMAL1 heterodimer has transcriptional activity for genes via the peroxisome proliferator-activated receptor response element (PPRE). Male mice 8-12 weeks old were maintained under a 12:12 hour light-dark cycle for at least two weeks before the day of the experiment. The mRNA profiles of BMAL1 and of the PPAR target genes acyl-CoA oxidase (AOX), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and cellular retinol binding protein II (CRBPII) were measured in intestine. The direct effects of CLOCK/BMAL1 on the promoter activities of those three enzymes were assessed in vitro by luciferase assay. The expression of PPAR target genes changed in a cyclical manner that followed expression of BMAL1. The promoter activities of the three enzymes were increased by CLOCK/BMAL1 expression. After deletion of the PPRE from the CRBPII construct, CLOCK/BMAL1 did not affect transactivation. CLOCK/BMAL1 transactivates PPAR target genes via the PPRE.

引用

页码：169 / 174

页数：6

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