Eating at odd hours raises risk of obesity, diabetes: Study

Eating at odd hours disrupts liver-brain signals, leading to obesity and metabolic disorders, a study reveals, highlighting potential therapeutic targets.

Eating at odd hours—a common pattern among shift workers and frequent travellers—can lead to obesity and metabolic disorders such as diabetes, according to a new study by scientists who have discovered a previously unknown communication channel between the liver and brain.

A person receives a free blood sugar test during a campaign to mark the World Diabetes Day in Dhaka, Bangladesh, November 14, 2024. (REUTERS)

The research by a team from Perelman School of Medicine at the University of Pennsylvania, and published in Science, reveals that the liver contains its own biological clock that sends precise signals to the brain through the vagus nerve, helping regulate when we feel hungry and choose to eat.

When this delicate timing mechanism is disrupted, it can trigger a cascade of metabolic disturbances that may contribute to weight gain and other health problems.

The insights were uncovered in experiments on mice. Researchers focused on a family of genes called REV-ERBs in liver cells. These genes play a crucial role in maintaining circadian rhythm—the body’s internal 24-hour clock that governs everything from sleep cycles to hormone release.

“Both mice and humans normally eat at times when they are awake and alert, and this circuit provides feedback from the liver to the central clock in the brain that keeps the system running smoothly,” said Dr Mitchell Lazar, director of Penn Medicine’s Institute for Diabetes, Obesity, and Metabolism, and the study’s senior author. “This feedback is through a nerve connection from the liver to the brain.”

When the research team disabled these genes in mice, effectively eliminating the liver’s timekeeping ability, they observed a dramatic shift in eating patterns. The mice began consuming significantly more food during their normal rest periods, mimicking the disrupted eating patterns seen in humans who work night shifts or experience jet lag.

The mechanism works through the vagus nerve, a complex network of neural fibres that connects major organs to the brain. The liver uses this neural pathway to communicate timing information to brain regions that control appetite and feeding behaviour. According to the research paper, “circadian desynchrony induced by shiftwork or jet lag is detrimental to metabolic health.”

Their findings reveal a homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns.

The implications of this discovery extend far beyond the laboratory. Metabolic disorders have become a pressing global health concern, affecting millions of people worldwide. These conditions, which include high blood pressure, elevated blood sugar, excess body fat around the waist, and abnormal cholesterol levels, significantly increase the risk of heart disease, stroke, and type 2 diabetes.

According to an Indian Council of Medical Research – India Diabetes (ICMR INDIAB) study published in 2023, India accounted for 101 million diabetics. Globally, in 2022, the number of diabetics was 830 million, according to data from the World Health Organization.

The research offers particular relevance for those who work unusual hours or maintain irregular eating schedules. These individuals, who often eat their main meals when their bodies expect to be sleeping, show higher rates of metabolic disorders compared to those who maintain regular eating patterns.

Importantly, the study also suggests potential therapeutic approaches. When researchers surgically interrupted the vagus nerve connection in obese mice, they observed a restoration of normal eating patterns and a reduction in food intake. “This suggests that targeting this liver-brain communication pathway could be a promising approach for weight management in individuals with disrupted circadian rhythms,” noted Lauren N Woodie, a post-doctoral researcher in Lazar’s lab.

The research team is now investigating the specific chemical signals the liver uses to communicate with the vagus nerve. The paper identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chronodisruption—the disruption of the body’s natural biological rhythms by environmental factors.

This discovery represents a significant advance in the understanding of how the body maintains metabolic homeostasis and suggests new approaches for addressing the growing global burden of metabolic disorders.