Summary: A new study highlights how signals from the liver to the brain influence eating patterns tied to our circadian rhythms. This liver-brain communication can become disrupted in people working night shifts or irregular hours, leading to weight gain and metabolic issues.
The research focused on a protein called REV-ERB in the liver that plays a role in regulating this internal clock. When disrupted, mice ate more during inactive hours, but restoring nerve connections improved eating patterns. This study suggests future therapies targeting liver-brain signals could help manage metabolic disorders in those with irregular schedules.
Key Facts
- Circadian Sync: Liver signals to the brain help align eating patterns with circadian rhythms.
- REV-ERB’s Role: This protein in liver cells aids in the body’s internal clock, crucial for healthy eating schedules.
- Potential Therapy: Targeting liver-brain signals may aid those with disrupted eating patterns due to night shifts or jet lag.
Source: University of Pennsylvania
People who work the nightshift or odd hours and eat at irregular times are more prone to weight gain and diabetes, likely due to eating patterns not timed with natural daylight and when people typically eat. But is it possible to stave off the ill effects of eating at these “unusual” times despite it not being biologically preferable?
A new study from the Perelman School of Medicine at the University of Pennsylvania says ‘yes’, and sheds light on how the body knows when to eat.
The study, published today in Science, explains how researchers discovered a connection between the liver’s internal clock and feeding centers in the brain.
The team’s research showed that the liver sends signals to the brain via the vagus nerve, letting the brain know if eating is happening at a time that follows the body’s circadian rhythm.
These signals can get disrupted from working unusual hours. The brain then overcompensates, leading to overeating at the wrong times.
“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 the study’s senior author, Mitchell Lazar, MD, PhD, the director of Penn Medicine’s Institute for Diabetes, Obesity, and Metabolism, and the Ware Professor of Diabetes and Metabolic Diseases.
“This feedback is through a nerve connection from the liver to the brain”.
Researchers specifically targeted genes called REV-ERBs in the liver cells of mice. REV-ERBs are important proteins that help regulate the body’s circadian rhythm. The body’s circadian rhythm is an internal 24-hour cycle that regulates various activities including sleep-wake cycles, hormone release, and eating habits.
When these REV-ERB genes were turned off in mice — making the liver have a faulty clock — eating patterns shifted dramatically, with more food consumed during less active times.
The effects were reversible. Cutting the nerve connection in obese mice restored normal eating patterns and reduced 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,” said Lauren N. Woodie, PhD, a post-doctoral researcher in Lazar’s lab.
The research team suggests that targeting specific parts of the vagus nerve could help people who work night shifts or experience jet lag by addressing overeating caused by disrupted body clocks.
“These findings open the door to future therapies that can target specific neural pathways to help those struggling with metabolic disorders caused by irregular eating schedules.
“Future research should focus on what kind of chemical signals the liver sends to the vagus nerve, to help us understand how the liver affects the brain and the body through this communication.”
Funding: The study was funded by the National Institutes of Diabetes, Digestive Diseases, and Metabolism, the JPB Foundation, and the Cox Medical Research Institute.
About this circadian rhythm research news
Author: Matthew Toal
Source: University of Pennsylvania
Contact: Matthew Toal – University of Pennsylvania
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Hepatic vagal afferents convey clock-dependent signals to regulate circadian food intake” by Mitchell Lazar et al. Science
Abstract
Hepatic vagal afferents convey clock-dependent signals to regulate circadian food intake
Circadian desynchrony induced by shiftwork or jet lag is detrimental to metabolic health, but how synchronous or desynchronous signals are transmitted among tissues is unknown.
We report that liver molecular clock dysfunction is signaled to the brain through the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN.
Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain.
Our findings reveal a homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns.
This identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chronodisruption.
