Disruptions between the brain's master circadian clock and the liver's internal clock, communicated via the hepatic afferent vagal nerve (HVAN), can lead to unhealthy eating patterns and increased weight gain, according to a new study in mice. The findings identify the neural link as a potential therapeutic target for obesity and metabolic dysfunction related to circadian disruption. In mammals, circadian rhythms are controlled by the suprachiasmatic nucleus (SCN) – a small part of the brain's hypothalamus that regulates the body's circadian rhythms.
This cycle triggers a feedback loop involving key clock genes that keep time in the body. Although the SCN manages overall timing, nearly all cells in the body – including those in the liver – have their own internal clocks. While the brain's master clock in the SCN is set by light cues, resulting in a ~24-hour cycle, the liver's molecular clock is especially responsive to eating patterns.
Synchronizing the light-based SCN clock with the liver's food-based clock is crucial for balanced metabolism. When these clocks fall out of sync, through shiftwork or jetlag experienced by humans, for example, it can lead to serious health issues, including a higher risk of cardiometabolic disease and type 2 diabetes. Although these consequences are well known, the mechanisms through which circadian desynchronization between the liver and brain occurs are poorly understood.
To explore the relationship between liver circadian rhythms and f.