|Wu, Nan - Baylor College Of Medicine|
|Kim, Kang Ho - Baylor College Of Medicine|
|Zhou, Ying - Baylor College Of Medicine|
|Lee, Jae Man - Baylor College Of Medicine|
|Kettner, Nicole - Children'S Nutrition Research Center (CNRC)|
|Mamrosh, Jennifer - Baylor College Of Medicine|
|Choi, Sungwoo - Baylor College Of Medicine|
|Fu, Loning - Children'S Nutrition Research Center (CNRC)|
|Moore, David - Baylor College Of Medicine|
Submitted to: Molecular Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/13/2016
Publication Date: 9/30/2016
Citation: Wu, N., Kim, K., Zhou, Y., Lee, J., Kettner, N.M., Mamrosh, J.L., Choi, S., Fu, L., Moore, D.D. 2016. Small heterodimer partner (NROB2) coordinates nutrient signaling and the circadian clock in mice. Molecular Endocrinology. 30(9):988-995.
Interpretive Summary: Our bodies adapt to changing circumstances over the the daily 24 hour cycle by a timing mechanism that is called the circadian clock. An important function of the circadian clock is to control metabolism, but the clock is also controlled by food. Changing the time of food availability can reset the timing of the circadian clock, but the way that nutrients reset the clock is not known. We learned that the expression of a nuclear receptor protein called SHP is increased in response to nutrients. This research shows that increased expression of SHP decreases expression an important component of the clock called Bmal. This mechanism contributes to the ability of nutrients to reset the clock. Disrupting the circadian clock by changing patterns of sleeping or eating is linked to obesity and metabolic problems. A better understanding of how food availability affects the clock will help us learn how to keep our clocks running smoothly.
Technical Abstract: 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.