Summary: A new study published in Science reveals how disruptions between the brain’s master clock and liver’s internal clock can lead to unhealthy eating patterns. Researchers found that a neural pathway, the hepatic vagal afferent nerve, plays a crucial role in coordinating these biological timekeepers, offering potential new approaches to treating obesity.
Journal: Science, November 8, 2024, DOI: 10.1126/science.adn2786 | Reading time: 4 minutes
The Body’s Timekeepers
Our bodies operate on multiple biological clocks, with the brain’s master timekeeper responding to light while the liver’s clock follows our eating patterns. When these internal timekeepers fall out of sync – as often happens with shift work or jet lag – it can lead to serious health problems.
In a breakthrough study published in Science, researchers have identified how miscommunication between these biological clocks can lead to overeating and weight gain. The study reveals the critical role of a neural pathway that could become a target for treating obesity.
A Tale of Two Clocks
The research team, led by Lauren Woodie and colleagues, investigated how the liver communicates with the brain to regulate eating patterns. Their work focused on the hepatic vagal afferent nerve (HVAN), which creates a two-way communication channel between these organs.
The scientists conducted experiments with mice, deleting specific clock genes in their liver cells. These mice showed disrupted eating patterns, consuming more calories during their rest phase and throughout the day.
Breaking the Circuit
In a crucial finding, the researchers discovered that surgically disconnecting the hepatic vagal nerve prevented overeating behaviors in mice with disrupted liver clocks. This intervention also reduced weight gain in mice fed a high-fat diet.
“The implication of the findings of Woodie et al. is that the circadian-disrupted liver sends signals to the arcuate nucleus to drive disordered eating and that this circuit explains the obesity seen in response to prevalent human circadian and sleep disruption,” write Noelia Martinez-Sanchez and David Ray in a related perspective piece.
Implications for Human Health
This discovery opens new possibilities for treating obesity, particularly in people whose circadian rhythms are disrupted by modern lifestyle factors. The identification of this specific neural pathway could lead to targeted therapies that help restore proper communication between the liver and brain clocks.
The research suggests that addressing circadian disruption through this newly identified pathway might offer an alternative approach to managing weight gain and metabolic disorders.
Glossary
• Circadian rhythm: The body’s 24-hour internal clock that regulates various biological processes
• Hepatic vagal afferent nerve (HVAN): A neural pathway that carries signals from the liver to the brain
• Suprachiasmatic nucleus (SCN): The brain’s master clock that regulates circadian rhythms
• Metabolic disorders: Conditions that disrupt normal metabolism and energy processing
Reader Comprehension Quiz
1. What happens when the liver’s clock and brain’s master clock become desynchronized?
Answer: It can lead to unhealthy eating patterns and increased weight gain.
2. How did researchers test the role of the liver clock in mice?
Answer: By deleting core clock components (REV-ERB⍺ and REV-ERBβ) in mouse liver cells.
3. What effect did cutting the hepatic vagal nerve have in mice?
Answer: It prevented overeating behaviors and reduced weight gain.
4. What sets the brain’s master clock versus the liver’s clock?
Answer: The brain’s clock responds to light cues, while the liver’s clock responds to eating patterns.
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