Neurons in brain’s timekeeper might control nighttime hunger
UTSW researchers’ findings could lead to new weight-loss strategies
DALLAS – Oct. 15, 2025 – Activating specific neurons in a part of the brain that serves as the body’s master circadian pacemaker caused mice to eat significantly more during a time of day when they would normally be at rest, a UT Southwestern Medical Center study shows. The findings, published in Cell Reports, could lead to new strategies to help people lose weight, including night shift workers who have a higher prevalence of obesity.
“We identify for the first time a distinct set of neurons in the brain that controls feeding and metabolism during one specific time of day and accounts for a small but not insignificant proportion of body weight,” said Jeffrey Zigman, M.D., Ph.D., Professor of Internal Medicine and Psychiatry at UT Southwestern. Dr. Zigman co-led the study with first author Omprakash Singh, Ph.D., a postdoctoral researcher in the Zigman Lab.
Researchers have long known that eating impacts body weight differently depending on when food is consumed, Dr. Zigman explained. For example, eating late at night is associated with greater weight gain than eating the same amount during the day. This effect is especially apparent in night shift workers, who are more frequently overweight or obese despite caloric intake similar to day workers.
These observations suggest specific circuits of neurons that affect feeding and metabolism might operate differently at various times of the day. Dr. Zigman, Dr. Singh, and their colleagues hypothesized that one such circuit might be in the suprachiasmatic nucleus (SCN), a part of the brain that sets circadian rhythms throughout the body based on light received through the eyes.
Previous research in the Zigman Lab showed that some SCN neurons are stimulated by ghrelin, a hormone that prompts feeding and slows metabolism to encourage weight gain. However, the significance of these findings had been unclear.
To better understand this population of SCN neurons, the researchers worked with mice genetically altered so the scientists could turn these neurons on and off. They found that if they turned on the neurons in the middle of the animals’ rest period – around 10 a.m., since mice are nocturnal – they ate more than two times as much as they usually do during this time. Turning the neurons off at this time reduced the already low amount of food typically consumed during this period.
Whether the neurons were on or off during other times of day or night had no effect on the rodents’ feeding behavior or weight. But turning the neurons off during their rest period for 15 straight days caused them to lose about 4.3% of their body weight, while mice with unaltered SCN neurons gained about 2.5%. These results suggest the activity of the ghrelin-stimulated SCN neurons is responsible for about 7% of body weight – a small but significant amount that could make a marked difference for overall health, Dr. Zigman said.
If these results also apply to humans, he added, they suggest that targeting the same population of neurons in the SCN could offer weight-loss benefits similar to those seen with some modern weight-loss drugs. This strategy could be especially beneficial for night shift workers and other groups to prevent or treat weight gain linked to nighttime eating.
Other UTSW researchers who contributed to this study are Kripa Shankar, Ph.D., Instructor in the Center for Human Nutrition and of Internal Medicine; Deepali Gupta, Ph.D., Instructor in the Peter O’Donnell Jr. Brain Institute and of Neuroscience; Luis Leon Mercado, Ph.D., Instructor of Internal Medicine; Sherri Osborne-Lawrence, M.S., Senior Research Scientist; Corine P. Richard, R.N.; Sepideh Sheybani-Deloui, Ph.D., and Salil Varshney, Ph.D., postdoctoral researchers; Soumya Kulkarni, B.S., Moyu Lyu, M.S., and Bingbing Li, B.S., graduate student researchers; Avi W. Burstein, high school student researcher; and Connor Lawrence, research assistant.
Dr. Zigman is a member of the Center for Hypothalamic Research and the Harold C. Simmons Comprehensive Cancer Center and an Investigator in the O’Donnell Brain Institute. He holds the Kent and Jodi Foster Distinguished Chair in Endocrinology, in Honor of Daniel Foster, M.D.; the Mr. and Mrs. Bruce G. Brookshire Professorship in Medicine; and The Diana and Richard C. Strauss Professorship in Biomedical Research.
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 24 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.