The link between mealtime, sleep and obesity is well known but poorly understood, with research showing that overeating can disrupt circadian rhythms and alter fatty tissue.
New research from Northwestern has shown for the first time that energy release may be the molecular mechanism by which our internal clocks control energy balance. From this understanding, scientists have also discovered that daytime is the ideal time in the light environment of the Earth’s rotation when it is most optimal to dissipate energy as heat. These findings have broad implications ranging from weight loss diets to sleep loss and how we feed patients who need long-term nutritional support.
The article, “Time-restricted eating alleviates obesity through adipocyte thermogenesis,” will be published online today and in print tomorrow (October 21) in the journal Science.
“It’s well known, though misunderstood, that insults to the body clock are going to be insults to the metabolism,” said study corresponding author Dr. Joseph T. Bass, Charles F Professor of Medicine Kettering at Northwestern University Feinberg School of Medicine. He is also a Northwestern Medicine endocrinologist.
“When animals consume Western-style cafeteria diets — high in fat and carbohydrates — the clock gets scrambled,” Bass said. “The clock is sensitive to the time people eat, especially in fatty tissue, and this sensitivity is suppressed by high-fat diets. We still don’t understand why, but what we do know is is that when animals become obese, they begin to eat more when they should be sleeping.This research shows why this is important.
Bass is also director of the Diabetes and Metabolism Center and chief of endocrinology in Feinberg’s Department of Medicine. Chelsea Hepler, a postdoctoral fellow at Bass Lab, was the first author and performed many of the biochemical and genetic experiments that founded the team’s hypothesis. Rana Gupta, now at Duke University, was also a key collaborator.
Jam the internal clock
In the study, mice, which are nocturnal, were fed a high-fat diet either exclusively during their inactive (light) period or during their active (dark) period. Within a week, mice fed during light hours gained more weight than those fed in the dark. The team also set the temperature to 30 degrees, where the mice expend the least energy, to lessen the effects of temperature on their findings.
“We thought there might be a component of energy balance where mice expend more energy eating at specific times,” Hepler said. “That’s why they can eat the same amount of food at different times of the day and be healthier when they eat during active times rather than when they should be sleeping.”
The increase in energy expenditure led the team to look at fat tissue metabolism to see if the same effect occurred in the endocrine organ. They found it did, and mice with genetically enhanced thermogenesis — or fat cell heat release — prevented weight gain and improved health.
Hepler also identified the futile creatine cycle, in which creatine (a molecule that helps maintain energy) undergoes chemical energy storage and release, in fatty tissue, implying that creatine can be the mechanism underlying the release of heat.
Intermittent fasting and gastric feeding tubes
The science is backed up by research done by Bass and his colleagues at Northwestern over 20 years ago that found a relationship between the internal molecular clock and body weight, obesity and metabolism in animals.
The challenge for Bass’s lab, which focuses on using genetic approaches to study physiology, has been understanding what it all means and finding the control mechanisms that produce the relationship. This study brings them a little closer.
The results could inform chronic care, Bass said, particularly in cases where patients have stomach tubes. Patients are usually fed at night while they sleep, when they release the least energy. Diabetes and obesity rates tend to be high in these patients, and Bass thinks that might explain why. He also wonders how the research might impact the treatment of type II diabetes. Should mealtimes be taken into account when administering insulin, for example?
Hepler will continue his research on creatine metabolism. “We need to understand how, mechanically, the circadian clock controls creatine metabolism so we can understand how to stimulate it,” she said. “Clocks do a lot for metabolic health at the fatty tissue level, and we don’t yet know how much.”
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