by Northwestern Medicine scientists have discovered the mechanism behind why eating late at night is linked to weight gain and diabetes.
The connection between mealtime, sleep, and obesity is well known but poorly understood, and research shows that overeating can disrupt circadian rhythms and change adipose tissue.
New Northwestern research has shown for the first time that energy release may be the molecular mechanism through which our internal clocks control energy balance. From this understanding, scientists also discovered that the day is the ideal time in the light environment of Earth’s rotation when it is most optimal to dissipate energy as heat. These findings have wide-ranging implications, from diet to sleep loss to how we feed patients who require long-term nutritional support.
The article, “Time-Restricted Eating Mitigates Obesity Through Adipocyte Thermogenesis,” will be published online today and in print tomorrow (Oct. 21) in the journal Sciences.
“It’s well known, though poorly understood, that insults to the biological clock are going to be insults to metabolism,” said the study’s corresponding author, Dr. Joseph T. Bass, the Charles F. Kettering Professor of Medicine in the College of Medicine. Feinberg of Northwestern University. Medicine. He is also an endocrinologist at Northwestern Medicine.
“When animals eat Western-style cafeteria diets (high in fat and carbohydrates), the clock speeds up,” Bass said. “The clock is sensitive to what time people eat, especially in fat tissue, and that sensitivity is lost with high-fat diets. We still don’t understand why, but what we do know is that as animals they get obese, they start eating more when they should be asleep. This research shows why that’s important.”
Bass is also director of the Center for Diabetes and Metabolism and chief of endocrinology in Feinberg’s department of medicine. Chelsea Hepler, a postdoctoral fellow at the Bass Lab, was the first author and did many of the biochemical and genetic experiments that supported the team’s hypothesis. Rana Gupta, now at Duke University, was also a key contributor.
Coding the internal clock
In the study, the mice, which are nocturnal, were fed a high-fat diet exclusively during their inactive (light) period or during their active (dark) period. Within a week, mice fed during daylight hours gained more weight compared to those fed in the dark. The team also set the temperature at 30 degrees, where the mice expend the least amount of energy, to mitigate the effects of temperature on their findings.
“We thought maybe there is 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 periods rather than when they should be sleeping.”
The increased energy expenditure prompted the team to investigate fat tissue metabolism to see if the same effect occurred within the endocrine organ. They found that it did, and the mice with genetically enhanced thermogenesis, or heat release through fat cells, prevented weight gain and improved health.
Hepler also identified the creatine waste cycle, in which creatine (a molecule that helps maintain energy) is stored and released chemical energy within fat tissues, implying that creatine may be the underlying mechanism of heat release.
Intermittent fasting and gastric feeding tubes
The science is backed up by research conducted by Bass and colleagues at Northwestern more than 20 years ago that found a relationship between the internal molecular clock and body weight, obesity and metabolism in animals.
The challenge for the Bass lab, which focuses on using genetic approaches to study physiology, has been to figure out what this all means and to find the control mechanisms that produce the relationship. This study brings them one step closer.
The findings could inform chronic care, Bass said, especially in cases where patients have gastric feeding tubes. Patients typically feed at night while sleeping, when they release the least amount of energy. Diabetes and obesity rates tend to be high for these patients, and Bass thinks this might explain why. She also wonders how the research might affect the treatment of type II diabetes. Should meal times be considered when administering insulin, for example?
Hepler will continue to investigate creatine metabolism. “We need to figure out how, mechanistically, the circadian clock controls creatine metabolism so we can figure out how to stimulate it,” he said. “Clocks are doing a lot for metabolic health at the level of fat 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 Professional Development Award (19CDA34670007).
