CLOCK/BMAL1 is involved in lipid metabolism via transactivation of the peroxisome proliferator-activated receptor (PPAR) response element
CLOCK/BMAL1 is involved in lipid metabolism via transactivation of the peroxisome proliferator-activated receptor (PPAR) response element
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DOI：
10.5551/jat.12.169
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发表时间：
2005-06-30
影响因子：
4.4
通讯作者：
Katayama, S
中科院分区：
文献类型：
--
作者：
Inoue, I;Shinoda, Y;Katayama, S
脂肪的吸收和代谢受摄食和昼夜节律系统的调节。已经表明，参与脂质代谢的酶的表达直接受生物钟系统控制。本研究旨在检查CLOCK/BMAL 1异二聚体是否通过过氧化物酶体增殖物激活受体反应元件（PPRE）对基因具有转录活性。将8-12周龄的雄性小鼠在实验前一天在12：12小时光-暗循环下维持至少两周。在肠道中测定BMAL 1和PPAR靶基因酰基辅酶A氧化酶（AOX）、3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）合酶和细胞视黄醇结合蛋白II（CRBPII）的mRNA表达谱。CLOCK/BMAL 1对这三种酶的启动子活性的直接作用通过荧光素酶测定在体外评估。在BMAL 1表达之后，PPAR靶基因的表达以周期性方式变化。CLOCK/BMAL 1表达增加了这三种酶的启动子活性。从CRBPII构建体中删除PPRE后，CLOCK/BMAL 1不影响反式激活。CLOCK/BMAL 1通过PPRE反式激活PPAR靶基因。
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.