Digestive Organs Have Separate Biologic Clocks From Brain’s Master Clock

MedicalResearch.com Interview with:

Dr. Hans Van Dongen, PhD Director of the Sleep and Performance Research Center. ELSON S. FLOYD COLLEGE OF MEDICIN Washington State University Spokane, WA


Dr. Hans Van Dongen, PhD
Director of the Sleep and Performance Research Center.
Washington State University
Spokane, WA

MedicalResearch.com: What is the background for this study?

Response: Night shift workers are at increased risk of metabolic disorders, including obesity and type 2 diabetes, as well as cardiovascular disease, chronic kidney disease, and cancer. Although it is believed that the biological clock – the master circadian clock in the brain – plays an important role in these adverse chronic health consequences of night shift work, the underlying mechanisms are not well understood.

MedicalResearch.com: What are the main findings? 

Response: In this laboratory study, 3 days on a simulated night shift schedule produced profound misalignment between the master circadian clock in the brain and peripheral clocks in organs involved in food metabolism. Participants were assigned to three days of either a simulated day shift schedule or a simulated night shift schedule. After completing their simulated shifts, all participants were kept in a constant routine protocol used to study internally generated biological rhythms independent of any external influences. During the constant routine protocol, the participants were kept awake for 24 hours in constant dim light and fixed room temperature and in a semi-reclined posture, while receiving identical snacks every hour, in order to eliminate any changes in external circumstances. Blood samples were drawn every 3 hours, and these samples were subjects to targeted metabolomics in order to measure the concentrations of a large number of feeding-related metabolites. After the three days on a simulated night shift schedule, the rhythms in many of the metabolites measured with shifted by approximately 12 hours– in sharp contrast with the master circadian clock, which was shifted by only about 2 hours  

MedicalResearch.com: What should readers take away from your report? 

Response: The study results show that

1) Organs involved in food metabolism – gut, liver, and pancreas – respond to shifted rhythms in behavior (sleeping, eating, being active) associated with night shift work;

2) In the absence of any changes in external circumstances, the rhythms of the biological clocks in these digestive organs – so-called peripheral clocks – reflect the behavioral cycles of the preceding days;

3) These rhythms can be observed using targeted metabolomics analysis of blood samples collected during a constant routine protocol;

4) The peripheral clocks in the digestive organs shift much more rapidly in response to prior night shift work than the master circadian clock;

5) This leads to desynchrony between the rapidly shifting peripheral clocks and the more slowly shifting master circadian clock, which may lead to disturbances in metabolism and may ultimately lead to the chronic metabolic disorders for which night shift workers are at increased risk.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: It remains to be investigated what aspect(s) of the shifted behavioral cycles in night shift work – the sleep/wake cycle, the feeding/fasting cycle, and/or the activity/rest cycle, is responsible for the shifted rhythms in peripheral clocks in the digestive system. It also remains to be investigated what signaling mechanisms are involved in conveying the timing of behavioral cycles to peripheral clocks in digestive organs. Further, studies of the impact of night work on metabolic health should take into account the rapid responsiveness of peripheral oscillators to shifted behavioral cycles.  

MedicalResearch.com: Is there anything else you would like to add?

Response: This study was a collaboration between Washington State University in the US and the University of Surrey in the UK. The research was funded in part by the US Department of Defense. The opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the US Department of Defense.


Debra J. Skene, Elena Skornyakov, Namrata R. Chowdhury, Rajendra P. Gajula, Benita Middleton, Brieann C. Satterfield, Kenneth I. Porter, Hans P. A. Van Dongen, Shobhan Gaddameedhi. Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism. Proceedings of the National Academy of Sciences, 2018; 201801183 DOI: 10.1073/pnas.1801183115


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