Mouse Study Finds Meal Timing Shapes Liver Rhythms Through mTOR

Meal timing helped shape daily gene activity in mouse liver through the nutrient-signaling pathway mTOR, according to a study published in Science Advances by researchers led by Jerome Menet of Texas A&M University. The findings separate the liver’s food-responsive rhythms from its core molecular circadian clock, while also showing how irregular feeding can disrupt those signals.

The researchers gave their models access to food during their normal active periods, creating a predictable feeding pattern that aligned with rhythmic mTOR activity. When the team blocked mTOR, rhythmic gene expression in the liver fell by 50%. Hundreds of genes that typically rise and fall over the course of a day lost those patterns.

The liver’s central circadian clock continued functioning, however. The result suggests that daily gene activity in the organ is controlled through at least two related systems: an intrinsic molecular clock and rhythmic signals generated by feeding. In this model, nutrients activated mTOR, which then helped transmit information about food availability to genes involved in liver activity.

The team also tested what happened when feeding became irregular and fell out of sync with the core circadian rhythm. Under those conditions, rhythmic mTOR activity in the liver also became irregular. Direct manipulation of mTOR restored the liver’s rhythmic gene-expression patterns to their baseline state, according to the researchers.

The study supports the idea that mTOR is more than a passive responder to meals. It may act as an intermediary between the timing of food intake and the timing of gene activity in the liver. The pathway responds to signals related to nutrient and energy availability and regulates processes including protein production, growth and metabolism, according to the researchers.

The findings provide a molecular framework for studying chrononutrition—the relationship between food timing and the body’s daily biological rhythms. The researchers said the work may help explain why behaviors such as night-shift work, late-night eating and irregular schedules can create conflicts between feeding signals and circadian timing. They connected those mismatches with possible relevance to metabolic and other health conditions, although the supplied report does not establish that the study demonstrated those diseases in humans.

The research was conducted in mouse liver, so it does not show that changing meal timing produces the same effects in people. It also does not establish that time-restricted eating or intermittent fasting improves human liver health or longevity. Instead, the findings identify mTOR as a potential target for further research into how feeding schedules influence biological timing and, according to the researchers, how the timing of medicines might eventually be coordinated with nutrient-driven liver rhythms.