Obesity afflicts approximately 42 percent of the U.S. adult population and contributes to the onset of chronic diseases, including diabetes, cancer, and other conditions.

While popular healthy diet mantras advise against midnight snacking, few studies have comprehensively investigated the simultaneous effects of late eating on the three main players in weight regulation and thus obesity risk: regulation of calorie intake, the number of calories you burn, and molecular changes in fat tissue.

A new study by Harvard Medical School investigators at Brigham and Women’s Hospital found that when we eat significantly impacts our energy expenditure, appetite, and molecular pathways in adipose tissue. Their results are published in Cell Metabolism.

“We wanted to test the mechanisms that may explain why late eating increases obesity risk,” explained senior author Frank Scheer, HMS professor of medicine and director of the Medical Chronobiology Program in the Division of Sleep and Circadian Disorders at Brigham and Women’s.

“Previous research by us and others had shown that late eating is associated with increased obesity risk, increased body fat, and impaired weight loss success. We wanted to understand why,” he said.

“In this study, we asked does the time that we eat matter when everything else is kept consistent,” said first author Nina Vujović , a researcher in the Medical Chronobiology Program.

Vujović, Scheer, and their team studied 16 patients with a body mass index in the overweight or obese range. Each participant completed two laboratory protocols: one with a strictly scheduled early meal schedule, and the other with the same meals, each scheduled about four hours later in the day.

In the last two to three weeks before starting each of the in-laboratory protocols, participants maintained fixed sleep and wake schedules, and in the final three days before entering the laboratory, they strictly followed identical diets and meal schedules at home.

“We found that eating four hours later makes a significant difference for our hunger levels, the way we burn calories after we eat, and the way we store fat.”

Nina Vujović

In the lab, participants regularly documented their hunger and appetite, provided frequent small blood samples throughout the day, and had their body temperature and energy expenditure measured.

To measure how eating time affected molecular pathways involved in adipogenesis, or how the body stores fat, investigators collected biopsies of adipose tissue from a subset of participants during laboratory testing in both the early and late eating protocols, to enable comparison of gene expression patterns/levels between these two eating conditions.

Results revealed that eating later had profound effects on hunger and the appetite-regulating hormones leptin and ghrelin, which influence our drive to eat. Specifically, levels of the hormone leptin, which signals satiety, were decreased across the 24 hours in the late eating conditions compared to the early eating conditions.

When participants ate later, they also burned calories at a slower rate and exhibited adipose tissue gene expression toward increased adipogenesis and decreased lipolysis, which promote fat growth.

Notably, these findings convey converging physiological and molecular mechanisms underlying the correlation between late eating and increased obesity risk.

Vujović explained that these findings are not only consistent with a large body of research suggesting that eating later may increase one’s likelihood of developing obesity, but they shed new light on how this might occur.

By using a randomized crossover study, and tightly controlling for behavioral and environmental factors such as physical activity, posture, sleep, and light exposure, investigators were able to detect changes in the different control systems involved in energy balance, a marker of how our bodies use the food we consume.

In future studies, Scheer’s team aims to recruit more women to increase the generalizability of their findings to a broader population. While this study cohort included only five female participants, the study was set up to control for menstrual phase, reducing confounding but making recruiting women more difficult.

Going forward, Scheer and Vujović are also interested in better understanding the effects of the relationship between mealtime and bedtime on energy balance.

“This study shows the impact of late versus early eating. Here, we isolated these effects by controlling for confounding variables like caloric intake, physical activity, sleep, and light exposure, but in real life, many of these factors may themselves be influenced by meal timing,” said Scheer.

“In larger scale studies, where tight control of all these factors is not feasible, we must at least consider how other behavioral and environmental variables alter these biological pathways underlying obesity risk, ” he said.

This study was funded by R01DK099512, UL1TR001102 and UL1TR002541. F.A.J.L.S. was supported by NIH grants R01DK099512, R01HL118601, R01DK102696, and R01DK105072 and R01HL140574. M.J.P. and M.J.B. were supported by DK020595. M.G. was supported by the Spanish Government of Investigation, Development and Innovation (SAF2017-84135-R), including FEDER co-funding; the Autonomous Community of the Region of Murcia through the Seneca Foundation (20795/PI/18), and NIDDK R01DK099512. S.L.C. was supported by the Alexander von Humboldt Foundation. J.Q. was supported by the American Diabetes Association (Award 1-17-PDF-103) and by the NIH (Grant K99HL148500 and R01DK102696).

Disclosures: During the execution of this project, Scheer received lecture fees from Bayer HealthCare, Sentara Healthcare, Philips, Vanda Pharmaceuticals, and Pfizer Pharmaceuticals; received consulting fees from the University of Alabama at Birmingham; and served on the board of directors for the Sleep Research Society. Scheer’s interests were reviewed and managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies. None of these are related to the current work. Vujović has been compensated for consulting services provided to the Novartis Institutes of BioMedical Research, also unrelated to the current work.