Wu Nan, Kim Kang Ho, Zhou Ying, Lee Jae Man, Kettner Nicole M, Mamrosh Jennifer L, Choi Sungwoo, Fu Loning, Moore David D
Department of Molecular and Cellular Biology (N.W., K.H.K., Y.Z., J.M.L., N.M.K., J.L.M., S.C., L.F., D.D.M.) and Program in Developmental Biology (S.C.), Baylor College of Medicine, Houston, Texas 77030; and Department of Biochemistry and Cell Biology (J.M.L.), School of Medicine, Kyungpook National University, Jung-gu, Daegu 41944, Republic of Korea.
Mol Endocrinol. 2016 Sep;30(9):988-95. doi: 10.1210/me.2015-1295. Epub 2016 Jul 18.
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.
昼夜节律调节多种代谢过程，反过来又很容易被进食-禁食周期所调节。然而，外周生物钟感知营养可用性的分子机制在很大程度上仍然未知。胆汁酸受昼夜节律控制，并且在餐后也会增加，作为肝脏进食状态的调节因子。在这里，我们表明核受体小异源二聚体伴侣（SHP），一种胆汁酸代谢的调节因子，通过直接调节Bmal1影响内源性外周生物钟。在Shp基因敲除小鼠中，依赖Bmal1的基因表达发生改变，并且在限制喂养时，Shp基因敲除小鼠的肝脏生物钟适应延迟。这些结果表明SHP是连接营养信号与昼夜节律钟的潜在介质。
