Northwestern Medicine scientists have uncovered the mechanism behind late-night eating linked to weight gain and diabetes.
The relationship between eating time, sleep and obesity is well known but not well understood, as research has shown that overfeeding can disrupt circadian rhythms and alter adipose tissue.
New Northwest research published in the journal Sciences showed for the first time that energy release may be the molecular mechanism by which our internal clocks control energy balance. From this understanding, the scientists also found that daytime is the ideal time in the light environment of the Earth’s rotation when the dissipation of energy as heat is optimal. These findings have broad implications from dieting to sleep loss and the way we feed patients who need long-term nutritional assistance.
“It is well known, if not well understood, that insults to the body clock would be an insult to metabolism,” said study corresponding author Dr. Joseph T. Bass, MD, professor of medicine at Northwestern University Feinberg. medicine. He is also an endocrinologist in Northwestern Medicine.
“When animals consume a Western-style cafeteria diet — high in fat and carbohydrates — the clock is ticking,” Bass said. “The clock is sensitive to what time people eat, especially in fatty tissue, and this sensitivity is thrown off by high-fat diets. We still don’t understand why this is, but what we do know is that when animals get obese, they start eating more when they should be asleep,” he explains. This research is why this is so important.”
Bass is also director of the Diabetes and Metabolism Center and chief of endocrinology in the Feinberg Department of Medicine. Chelsea Heppler, a postdoctoral fellow in the Bass lab, was first author and performed several biochemistry and genetics experiments that established the team’s hypothesis. Rana Gupta, now at Duke University, was also a key collaborator.
scrambling the internal clock
In the study, mice, which were nocturnal, were fed a high-fat diet either exclusively during their inactivity (light) period or during their active (dark) period. Within a week, mice fed during the light hours gained more weight compared to those fed in the dark. The team also set the temperature to 30 degrees, with the mice consuming the least amount of energy to mitigate the effects of temperature on their findings.
“We thought there might be an element of energy balance where the mice expend more energy eating at specific times,” Hepler said. “This is why they can eat the same amount of food at different times of the day and be healthier when they eat during periods of activity versus when they should be sleeping.”
The increase in energy expenditure led the team to look at the metabolism of adipose tissue to see if the same effect occurred within the endocrine organ. They found that mice with genetically enhanced thermogenesis — or the release of heat through fat cells — prevented weight gain and improved health.
Hepler also identified the useless creatine cycle, in which creatine (a molecule that helps conserve energy) undergoes chemical energy storage and release, within fat tissue, implying that creatine may be the mechanism behind heat release.
Results can benefit chronic care
This science is based on research conducted by Bass and 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 methods to study physiology, was to discover what it all means, and to find the control mechanisms that produce the relationship. This study brings them one step closer.
Bass said the findings could benefit chronic care, especially in cases where patients have gastric feeding tubes. Patients usually feed at night while they sleep, when they release the least amount of energy. Rates of diabetes and obesity tend to be higher for these patients, and Bass thinks this may explain why. He also wonders how the research might affect the treatment of type 2 diabetes. Should meal times be considered when giving insulin, for example?
Hepler will continue to research creatine metabolism. “We need to know how the biological clock mechanically controls creatine metabolism so we can figure out how to boost it,” she said. “Watches do a lot for metabolic health at the adipose tissue level, and we don’t know to what extent yet.”
Research support was provided by the National Institute of Diabetes and Digestive and Kidney Diseases (grants R01DK127800, R01DK113011, R01DK090625, F32DK122675, F30DK116481, F31DK130589, K99DK124682, R01DK104789, National Institute of Professional Development and R01DK104789DA) Award P01AG01.