Nuclear receptor expression links the circadian clock to metabolism
Nuclear receptor expression links the circadian clock to metabolism
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DOI：
10.1016/j.cell.2006.06.050
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发表时间：
2006-08-25
期刊：
影响因子：
64.5
通讯作者：
Evans, Ronald M.
中科院分区：
文献类型：
--
作者：
Yang, Xiaoyong;Downes, Michael;Evans, Ronald M.
作为脂溶性激素和膳食脂质的传感器，核受体（NR）在关键代谢组织中表达的振荡可能有助于营养和能量代谢的昼夜夹带。调查的昼夜表达谱的所有49个小鼠核受体在白色和棕色脂肪组织，肝脏和骨骼肌显示，45个NR的表达，25个是在一个有节奏的周期和3个表现出一个单一的瞬时脉冲的表达4小时进入光周期。虽然甲状腺激素通常是恒定的，我们发现TR α和β显着循环，这表明基本概念，如“基础代谢”可能需要重新检查。核受体表达的动态但协调的变化，沿着它们的关键靶基因，为已知的脂质和葡萄糖代谢的循环行为提供了合乎逻辑的解释，并表明内分泌和孤儿受体在将外周生物钟与不同的代谢输出耦合中的新作用。
As sensors for fat-soluble hormones and dietary lipids, oscillations in nuclear receptor (NR) expression in key metabolic tissues may contribute to circadian entrainment of nutrient and energy metabolism. Surveying the diurnal expression profiles of all 49 mouse nuclear receptors in white and brown adipose tissue, liver, and skeletal muscle revealed that of the 45 NRs expressed, 25 are in a rhythmic cycle and 3 exhibit a single transient pulse of expression 4 hr into the light cycle. While thyroid hormones are generally constant, we find that TR alpha and beta dramatically cycle, suggesting that fundamental concepts such as "basal metabolism" may require reexamination. The dynamic but coordinated changes in nuclear receptor expression, along with their key target genes, offers a logical explanation for known cyclic behavior of lipid and glucose metabolism and suggests novel roles for endocrine and orphan receptors in coupling the peripheral circadian clock to divergent metabolic outputs.