Sleeping during the day and staying up all night will impact the concentration and activity of over 100 proteins in the blood — even if you only do it for short while.

Staying awake and eating during the night throws a wrench in the activity of blood-borne proteins, according to new research from the University of Colorado Boulder. The proteins identified by the team impact processes involved in a wide array of metabolic functions, from blood sugar levels to immune function. The study is the first to examine how protein levels in human blood, also known as the plasma proteome, vary over a 24-hour period and how altered sleep and meal timing affects them.

Protein shift

“This tells us that when we experience things like jet lag or a couple of nights of shift work, we very rapidly alter our normal physiology in a way that if sustained can be detrimental to our health,” said senior author Kenneth Wright, director of the Sleep and Chronobiology Laboratory and Professor in the Department of Integrative Physiology.

The team enlisted the help of six healthy male subjects in their 20s for the study. The participants were asked to spend six days at the university’s clinical translational research center. While here, their meals, sleeping hours, active periods and the hours they were exposed to light were tightly controlled and recorded.

On the first two days, the men were kept on a normal schedule: active hours and light exposure during the day, sleeping hours at night. They were then gradually transitioned to a night-shift work pattern —  they could get an eight-hour sleep if they wanted, but only during the day, and stayed up and ate at night. The team collected blood samples every four hours, which they analyzed for the concentrations and time-of-day-patterns of 1,129 proteins.

They report that 129 of these proteins’ patterns were thrown off by the simulated night shift. The effect was already noticeable by the second day of night-shift waking patterns, Depner adds.

One of the affected proteins was glucagon — which tells the liver to inject sugar into the bloodstream. Glucagon levels in the blood peaked during waking hours, the team found, meaning they shifted to night-hours as the participants started staying awake at night. But it also peaked in higher concentrations, the team adds. They think that this effect could, in the long-term, form the root cause of the higher diabetes rates seen in night-shift workers.

Night-shift wakefulness patterns also decreased blood levels of fibroblast growth factor 19. Previous research with animal models has shown this protein to boost calorie-burning and energy expenditure, the team adds. The participants in this study burned 10% fewer calories per minute when their schedule was misaligned.

Overall, thirty proteins showed a clear 24-hour-cycle, most showing a peak between 2 p.m. and 9 p.m.

“The takeaway: When it comes to diagnostic blood tests—which are relied upon more often in the age of precision medicine—timing matters,” said senior author Kenneth Wright.

The authors note that all the participants were kept in dim light conditions, to eliminate the effect of light-exposure (which can also strongly affect the circadian system) on the results. Even without the glow of electronics at night, changes in protein patterns were rapid and widespread.

“This shows that the problem is not just light at night,” Wright said. “When people eat at the wrong time or are awake at the wrong time that can have consequences too.”

The findings could lead to new treatment options for night shift workers, who are at a higher risk for diabetes and cancer. It could also enable doctors to precisely time administration of drugs, vaccines and diagnostic tests around the circadian clock.

The paper “Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome” has been published in the journal PNAS.

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