Shifted waking hours may pave the way to shifting metabolism

Shift work can be brutal. Working late nights, early mornings and constantly changing hours wreaks havoc on social and family life. But in our racing, 24-hour world, someone needs to keep the lights on. For years, scientists have studied just what happens when we play fast and loose with the body’s clock. A handful of new studies add to the evidence that shift work and other kinds of circadian disruption shifts not just our hours but also our metabolic function, making future work schedules and policies a weighty matter for our health.

More than 15 million Americans work the evening shift, graveyard shift or rotating shifts that alternate between day and nighttime hours. But most people are going against their circadian clocks when they try to stay up all night. “The whole reason we have a clock is to link us to the solar day,” says Ilia Karatsoreos, a neuroscientist at Washington State University in Pullman. “Even the simplest single-celled organisms have clocks that organize their physiology. These are really ancient systems.” The clocks in our bodies not only tell us when to wake and sleep, they also help organize everything from our appetites to our hormones.

All of these systems start to go awry when we stay up all night. Given enough time on a single schedule, a person can adjust to being a full-time night owl. But many people, even if they work nights full time, want to spend time with their day-dwelling family and friends, so their clocks never truly adjust. The result? Higher body mass index and increased risk for metabolic syndrome, as well as increased risk for cancer and, of course, sleep disorders.

Karatsoreos and his colleagues have been studying the link between shift work, body mass index, and metabolic disorders. In 2011, Karatsoreos’ group shifted mice onto a 20-hour cycle instead of a 24-hour cycle, a way to cause circadian disruption that the animals never quite adjusted to, even over a period of 10 weeks. The animals gained weight and had higher levels of insulin, suggesting they might be headed toward type 2 diabetes. Karatsoreos says that it’s not just that shift workers – or time-shifted mice – eat more. Instead, “they eat food at the wrong times, and so they [could be] affected more by high fat diets,” he says. “Things conspire together to increase weight gain and changes in metabolic function.” Karatsoreos and his colleagues published the findings in January 2011 in the Proceedings of the National Academy of Sciences.

But exactly how shifting schedules nudge metabolic systems is still unclear. Metabolic hormones such as insulin exhibit 24-hour cycles. Along with insulin, our sensitivity to blood glucose also changes. We have the best sensitivity to blood glucose in the morning, and the least at night. Scientists also know that shift workers are much more likely to show signs of high blood glucose. But most of these studies are surveys. It can be hard to tell, without deliberately disrupting people’s sleep, just how much the shift work itself contributes to metabolic problems.

In a small study run by Christopher Morris and Frank Scheer at Harvard Medical School, 14 people came into the lab for two sessions of eight days. During one of the sessions, the participants ate at 12-hour intervals, and otherwise simply lived in the lab, with lights out at night between 11 p.m. and 7 a.m. During the other eight-day session, the volunteers suffered a multiple time zone shift. After three days the lights began to reverse, with darkness between 11 a.m. and 7 p.m.

After only three days of this time-shifting, people had high blood glucose levels in both the morning and the evening. They showed signs of reduced sensitivity to insulin – a warning sign of metabolic problems. “We are starting to see how tremendously interconnected the circadian and metabolic pathways are,” Scheer says. Morris and Scheer and their colleagues published the results April 13 in the Proceedings of the National Academy of Sciences.

Shift work and other types of circadian disruption are obviously not the only variables that contribute to obesity. “I don’t think any one factor will be the smoking gun for obesity,” says Michael Parsons, a behavioral geneticist at the Medical Research Council Harwell in England.  “But I do think it’s important to such a public health-related topic as obesity to know all the factors involved. It shows that a relatively small stressor [circadian disruption] that’s chronic can have consequences.”

The way that shift workers handle mealtime might provide both insight into how our body clocks function and a better understanding of how to protect the health of people who work in a world that needs to run 24/7. “We think the feeding cycle may the most important aspect of this,” Scheer says. “Shift work is not going to go away, people will continue to do it, it’s not like we can just hide from the problem.”

With further research into metabolic hormone cycles, he says, drugs might be developed that could treat some of the metabolic side effects of shift work. But drugs themselves have their own issues. In the end, Scheer thinks behavioral change might be the best bet, with shift workers controlling when they eat to fit with an unadjusted body clock, rather than matching their waking hours. “It’s better to go to the root cause of what is driving the adverse metabolic effects and tackle the effect with behavior.” But that is something that can only be understood with more work, to find out how and why we eat and sleep when we do.