According to a new study by the University of Colorado Boulder, pulling an all-nighter just once can disrupt levels and time of day patterns of more than 100 proteins in the blood. This suggests that proteins altered during circadian misalignment are associated with biological pathways involved in immune function, metabolism, and cancer and with altered glucose and energy metabolism.
This is the first study that suggests how protein levels in human blood, otherwise called the plasma proteome, change over a 24-hour time period and how altered sleep and meal timing influences them. The findings are expected to discover a new potential treatment for night shift workers, who make up about 20 percent of the global workforce and are at higher risk for diabetes and cancer.
Lead author Christopher Depner, a postdoctoral researcher in the Department of Integrative Physiology said, “If we know the proteins that the clock regulates, we can adjust the timing of treatments to be in line with those proteins. It could also enable doctors to precisely time administration of drugs, vaccines and diagnostic tests around the circadian clock.”
Scientists volunteered 6 healthy male subjects and ask them to spend six days in the clinical translational research center at the University of Colorado Hospital. During the study period, their meals, sleep, activity and light exposure were tightly controlled.
On days one and two, the men stuck to a normal schedule. Then they were gradually transitioned to a simulated night-shift work pattern, in which they had the opportunity to sleep for eight hours during the day and stayed up all night, eating them.
Scientists used blood monitoring technology recently developed at Boulder-based SomaLogic Inc to assess levels and time-of-day-patterns of 1,129 proteins. They found 129 proteins whose patterns were thrown off by the simulated night shift.
Depner said, “By the second day of the misalignment we were already starting to see proteins that normally peak during the day peaking at night and vice versa. One of those proteins was glucagon, which prompts the liver to push more sugar into the bloodstream. When subjects stayed awake at night, levels not only surged at night instead of a day but also peaked at higher levels. Long term, this pattern could help explain why night-shift workers tend to have higher diabetes rates”
Kenneth Wright, director of the Sleep and Chronobiology Laboratory and professor in the Department of Integrative Physiology said, “The simulated night shift schedule also decreased levels of fibroblast growth factor 19, which has been shown in animal models to boost calorie burning or energy expenditure. This fell in line with the finding that subjects burned 10 percent fewer calories per minute when their schedule was misaligned.”
“Thirty proteins showed a clear 24-hour-cycle, with the majority peaking between 2 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.”
The study was conducted in dim-light conditions, so that light exposure didn’t influence results. Even without the glow of electronics at night, changes in protein patterns were rapid and widespread.
Wright said, “This shows that the problem is not just light at night. When people eat at the wrong time or are awake at the wrong time that can have consequences too.”
The research is published in the Proceedings of the National Academy of Sciences (PNAS) this week.