Individuals who work night shifts or have non-traditional hours and often eat at unpredictable times are at a greater risk for weight gain and diabetes. This is primarily due to their eating habits clashing with natural daylight and societal meal patterns. However, is there a way to mitigate the negative consequences of dining at these “unusual” hours, even if it doesn’t align with our biological preferences? A recent study from the Perelman School of Medicine at the University of Pennsylvania offers a positive answer, revealing how our bodies determine when it’s time to eat. This research, published in Science, highlights the link between the liver’s internal clock and the brain’s feeding centers.
The research team found that the liver communicates with the brain through the vagus nerve, signaling whether food is being consumed at times aligned with the body’s natural circadian rhythm. Working atypical hours can disrupt these signals. As a result, the brain may react by trying to compensate, which can lead to overeating at inappropriate times. “Both mice and humans typically eat during waking hours when they are alert, and this circuit offers feedback from the liver to the brain’s central clock, keeping everything working properly,” explained the study’s senior author, Mitchell Lazar, MD, PhD, who directs Penn Medicine’s Institute for Diabetes, Obesity, and Metabolism, and holds the Ware Professorship of Diabetes and Metabolic Diseases. “This feedback operates through nerve connections linking the liver and brain.”
Researchers honed in on specific genes known as REV-ERBs within the liver cells of mice. These proteins play a crucial role in maintaining the body’s circadian rhythm, which is a 24-hour internal cycle that regulates several functions, including sleep, hormone production, and eating patterns. When the REV-ERB genes in the liver were deactivated in mice—resulting in an impaired circadian clock—eating habits drastically changed, with increased consumption occurring during less active periods.
Fortunately, the effects were reversible. Severing the nerve connection in obese mice led to a return to normal eating habits and a decrease in food consumption. “This indicates that focusing on the communication pathway between the liver and brain could provide a new strategy for managing weight in those with disrupted circadian cycles,” noted Lauren N. Woodie, PhD, a post-doctoral researcher in Lazar’s lab.
The research team proposes that by targeting specific areas of the vagus nerve, it may be possible to assist individuals working night shifts or dealing with jet lag to reduce overeating that results from disrupted body clocks. “These discoveries pave the way for future treatments aimed at specific neural pathways to support those facing metabolic challenges due to irregular eating schedules. Subsequent research should identify the types of chemical signals sent from the liver to the vagus nerve, enhancing our understanding of how the liver influences the brain and body through this connection.”
This study received funding from the National Institutes of Diabetes, Digestive Diseases, and Metabolism, the JPB Foundation, and the Cox Medical Research Institute.
