WSU Researchers Make Surprising Finding in Fatigue/Metabolism Study

Jul 12, 2018

WSU Spokane sleep scientist Hans Van Dongen looks at data tables he plotted for research that brought surprising results.

“Ah ha” moments don’t happen very often for scientists, but world-renowned sleep researcher Hans Van Dongen at WSU Spokane experienced one recently.

One of Van Dongen’s emphases is looking at the physiological effects of working swing and graveyard shifts.

People were meant to be active during the day and to sleep at night. And when that order is reversed or somehow altered, it throws off a person’s internal clock. That can lead to big problems, for example, if a tired person with some important responsibility makes a mistake on the job. He and others also say people who work odd shifts also face a greater chance of contracting diabetes and becoming obese.

Van Dongen and some colleagues were doing a study recently with 14 participants. Each spent a week inside the campus sleep lab. Half would simulate doing work for three days on the night shift, while the others did a three days on the day shift. They fed them the same things. They monitored their metabolism. They drew blood every three hours.

“We are looking at the effects of shift work on people’s heart rate and heart rate variability," Van Dongen said. "Then we got this wonderful opportunity to also take blood samples and send those to our colleagues at the University of Surrey in the UK. And they looked at the blood samples and did what is called targeted metabolomics on them.

"What that means is they had the ability, with very modern equipment, to look at a whole bunch of metabolites, specifically metabolites related to how we digest our food. These are substances that are circulating in blood that have been previously been very difficult to assess and we could look at a whole bunch of them and they tell us something about how food is being processed in the body. We have known for a long time that the metabolites we were looking at have rhythms, just like many other things in the body," he said.

"What we were expecting to see, not thinking too hard about it because this was just an opportunity we got later, but what we were expecting to see was these rhythms in the metabolites would follow the biological clock, the master clock in the brain," Van Dongen said. "We call it a master clock for a reason; it drives all the rhythms in the body and the master clock is the primary reason why people who are shift workers are sleepy during the night when they’re supposed to work and also have difficulty sleeping during the day when the body tells them to be awake and they’re trying to catch up on sleep.”

A couple of weeks after sending the blood samples to the UK, the researchers there sent back the results. Van Dongen sat at his computer to plot the numbers onto graphs.

“What we found was that the rhythms in the metabolites in the night workers were flipped completely, such that these rhythms in these metabolites had adapted to the night work schedules almost completely, whereas the biological clock in the brain hadn’t adapted much at all and we never saw that coming,” he said.

Translated: the gut, the system that digests our food has its own clock, distinct from the master clock in the brain.

“What it was telling us is that there’s something else in the body that’s keeping track of rhythms also," Van Dongen said. "In addition to the biological clock in the brain, there’s parts of the gut, the liver and the pancreas that are also keeping time for the body, completely separate from the biological clock. Those clocks adapt to the night work schedule very quickly. And that completely changes the picture of what is actually the problem in shift workers.

"Now what we’ve learned is the clocks in the body adapt, the clock in the brain does not. It’s the desynchrony between those clocks, between the body and the brain, that’s causing the metabolic disruption that ultimately, we think now, leads to obesity, to diabetes and to other cardiovascular problems in shift workers. Completely different story than what we ever thought it would be," he said.

“It changes our perspective on how this works," Van Dongen said.

WSU cancer researcher Shobhan Gaddameedhi is exploring the potential link between shift work and cancer.
Credit WSU College of Pharmacy

One of his colleagues in the study is WSU College of Pharmacy assistant professor Shobhan Gaddameedhi. He’s a cancer researcher. He says not only are people who work the night shift susceptible to obesity and diabetes, but cancer as well.

“There is strong evidence that people who do long-term shift work are suffering from various types of cancer, especially skin cancers and breast cancers and prostate cancer in men and there is a strong correlation," Gaddameedhi said. "Understanding how this shift work influences this, potentially you can prevent it if you identify the connection.”

The WSU study was published this week in the online version of the journal Proceedings of the National Academy of Sciences.