Circadian Disruptions and Overeating: Can Targeting the Liver-Brain Pathway Help?

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People who work night shifts or irregular hours and eat at inconsistent times are more susceptible to weight gain and diabetes, likely because their eating patterns don't align with natural daylight or typical meal times. However, a new study from the Perelman School of Medicine at the University of Pennsylvania suggests it's possible to mitigate the negative effects of eating at these "off" times, even if it's not biologically ideal. Published in Science, the study reveals how researchers found a link between the liver's internal clock and the brain's feeding centers, shedding light on how the body regulates when to eat ().

Liver-Brain Communication and Circadian Rhythms

The research team found that the liver communicates with the brain through the vagus nerve, signaling whether eating is occurring at a time that aligns with the body's natural circadian rhythm. When people work irregular hours, this communication can become disrupted, causing the brain to overcompensate by triggering overeating at inappropriate 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, M.D., Ph.D., 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."

‘Did You Know?
Liver makes up around 2% of an adult's body weight. The liver is unique due to its dual blood supply from the portal vein and the hepatic artery. #medindia #liver #weight’

Targeting REV-ERB Genes to Study the Liver's Circadian Rhythm

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.

Potential for Liver-Brain Communication to Aid Weight Management

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, Ph.D., a post-doctoral researcher in Lazar's lab.

Towards New Therapies for Metabolic Health

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."

Reference:

1. Rhythmic liver drives feeding behavior - (https:www.science.org/doi/10.1126/science.adt0743)

Source: Eurekalert