Monday 18 June 2018

The circadian proteome

For the first time it has been investigated how the protein levels in our blood fluctuate during a 24-hour period and what impact a disrupted circadian rhythm has on this. It was found in any case to have implications for blood sugar levels, energy metabolism and immune function.

A reverse sleep-wake cycle disrupts our protein production; glucagon and fibroblast growth factor 19 become dysregulated as a result of this, which can lead to health problems. 


Study design

As part of this study performed at the University of Colorado Boulder, six healthy young men stayed at a research centre for six days. Diet, activity, sleep and exposure to (gradually reducing) light were monitored. The first two days followed the normal day-night rhythm, they were then gradually switched to simulated night shifts. Their blood was sampled every four hours, to test 1129 proteins; 129 of these exhibited disrupted patterns. Just a couple of days of a disrupted biological clock caused by a reverse sleep and mealtime rhythm dysregulates the levels of no less than 100 proteins. In addition, 30 proteins were identified which did continue to follow our internal circadian clock, irrespective of our sleep and mealtime rhythm.


The implications for health 

On the second day of the reverse sleep-wake rhythm, the proteins that usually peak during the day started to peak at night and vice versa. Glucagon levels, important for the regulation of blood sugar levels, became disrupted and the peak was higher. This may well be why night-shift workers are more likely to develop diabetes. The level of fibroblast growth factor 19, which in animal models stimulate calorie burning and energy consumption, fell. This would explain why, during the disrupted circadian rhythm,  the trial subjects burned ten percent fewer calories.But the whole day-night rhythm of the proteome was not disrupted: 30 proteins continued to follow the internal clock. This will possibly lead to additional disruption because certain proteins are suddenly released at the same time, instead of interspersed. In short: proteins that regulate the sugar levels, energy metabolism and immune function are disrupted by a reverse circadian rhythm, with the associated consequences.


In practice 

These findings can help to reduce the risk of disease in night-shift workers. Furthermore, it can provide guidance to doctors to decide on the best time to administer medication and vaccines. The timing of treatments and diagnostic tests can be aligned with the protein levels that are regulated by the circadian clock. This means that treatments and test results will be more effective.



Depner CM, Melanson EL, McHill AW, Wright KP Jr. Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome. PNAS June 5, 2018. 115 (23) E5390-E5399; published ahead of print May 21, 2018.