Health benefits come from eating during the daytime, demonstrating a potential link to energy release — ScienceDaily

Researchers from Northwestern Medicine have revealed the mechanism behind why eating late at night is linked to weight gain and diabetes.

The link between eating time, sleep and obesity is well known but poorly understood, with research showing that overeating can disrupt circadian rhythms and alter adipose 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, the researchers also found that daytime is the ideal time in the light environment for the Earth’s rotation when it is most optimal to dissipate energy as heat. These findings have broad implications from dieting to sleep loss and how we feed patients who need long-term nutritional support.

The paper, “Time-restricted feeding mitigates obesity through adipocyte thermogenesis,” will be published online today and in print tomorrow (October 21) in the journal Science.

“It is well known, if poorly understood, that insults to the body clock will be insults to metabolism,” said corresponding study author Dr. Joseph T. Bass, Charles F. Kettering Professor of Medicine at Northwestern University Feinberg School of Medicine. He is also an endocrinologist at Northwestern Medicine.

“When animals eat Western-style cafeteria diets — high fat, high carb — the clock gets distorted,” Bass said. “The clock is sensitive to the time people eat, especially in adipose tissue, and that sensitivity is thrown off by high-fat diets. We still don’t understand why that is, but what we do know is that when animals get fat, they start eating more when they should sleep. This research shows why it’s important.”

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Bass is also director of the Center for Diabetes and Metabolism and director of endocrinology in the Department of Medicine at Feinberg. Chelsea Hepler, a postdoctoral fellow in the Bass Lab, was the first author and did many of the biochemistry and genetics experiments that founded the team’s hypothesis. Rana Gupta, now at Duke University, was also an important collaborator.

Distort 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 compared to those fed in the dark. The team also set the temperature to 30 degrees, where mice expend the least energy, to mitigate the effects of temperature on their findings.

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“We thought there might be a component of energy balance where mice spend 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 periods compared to when they should be sleeping.”

The increase in energy expenditure led the team to examine the metabolism of adipose tissue to see if the same effect occurred in the endocrine organ. They found that it did, and mice with genetically enhanced thermogenesis — or heat release through fat cells — prevented weight gain and improved health.

Hepler also identified futile creatine cycling, where creatine (a molecule that helps maintain energy) undergoes storage and release of chemical energy in adipose tissues, suggesting that creatine may be the mechanism behind heat release.

Intermittent fasting and gastric feeding tubes

The science is backed up by research done by Bass and colleagues at Northwestern more than 20 years ago that found a link 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 to figure out what it all means and to find the control mechanisms that produce the relationship. This study brings them one step closer.

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The findings could inform chronic care, Bass said, especially in cases where patients have gastric feeding tubes. Patients are usually fed at night while they sleep, when they release the least amount of energy. Diabetes and obesity rates tend to be high for these patients, and Bass believes this may explain why. He also wonders how the research can affect the treatment of type II diabetes. Should mealtimes be considered when giving insulin, for example?

Hepler will continue to research creatine metabolism. “We need to figure out how, mechanistically, the circadian clock controls creatine metabolism so we can figure out how to increase it,” she said. “Clocks do a lot for metabolic health at the level of adipose tissue, and we don’t know how much yet.”

Research support was provided by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (grants R01DK127800, R01DK113011, R01DK090625, F32DK122675, F30DK116481, F31DK130589, K99DK124682, R01DK104789 and R01DK119163), the National Institute on Aging (grants R01AG065988 and P01AG011412 ) and the American Heart Association Career Development Award (19CDA34670007).

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