Small Heterodimer Partner (NR0B2) Coordinates Nutrient Signaling and the Circadian Clock in Mice.
Small Heterodimer Partner (NR0B2) Coordinates Nutrient Signaling and the Circadian Clock in Mice.
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DOI：
10.1210/me.2015-1295
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发表时间：
2016-07
影响因子：
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通讯作者：
Nan Wu;K. Kim;Ying Zhou;J. M. Lee;N. Kettner;Jennifer L Mamrosh;Sungwoo Choi;L. Fu;D. Moore
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文献类型：
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作者：
Nan Wu;K. Kim;Ying Zhou;J. M. Lee;N. Kettner;Jennifer L Mamrosh;Sungwoo Choi;L. Fu;D. Moore
昼夜节律调节多种新陈代谢过程，进而很容易受到喂食-禁食循环的影响。然而，外周生物钟感知营养供应的分子机制在很大程度上仍不清楚。胆汁酸在昼夜节律的控制下，也在餐后增加，作为肝脏中饲料状态的调节器。在这里，我们展示了核受体小杂二聚体伙伴(SHP)，胆汁酸代谢的调节因子，通过直接调节BMal1来影响内源性外周时钟。在SHP基因敲除的小鼠中，BMal1依赖的基因表达发生改变，在限制喂养的SHP基因敲除小鼠中，肝脏时钟的适应被延迟。这些结果表明，SHP是连接营养信号和生物钟的一个潜在的中介。
Circadian rhythm regulates multiple metabolic processes and in turn is readily entrained by feeding-fasting cycles. However, the molecular mechanisms by which the peripheral clock senses nutrition availability remain largely unknown. Bile acids are under circadian control and also increase postprandially, serving as regulators of the fed state in the liver. Here, we show that nuclear receptor Small Heterodimer Partner (SHP), a regulator of bile acid metabolism, impacts the endogenous peripheral clock by directly regulating Bmal1. Bmal1-dependent gene expression is altered in Shp knockout mice, and liver clock adaptation is delayed in Shp knockout mice upon restricted feeding. These results identify SHP as a potential mediator connecting nutrient signaling with the circadian clock.