Scientists have linked the time of meals with the rhythms of the liver

Not only the composition and quantity of food, but also the time of its intake can affect how the liver processes nutrients. This conclusion was reached by researchers who studied daily changes in liver metabolism in mice and the role of the ACSF3 enzyme associated with mitochondrial function. Scientists have found that changing the diet shifts the activity of this enzyme and related processes in the liver. How the time of a meal affects the metabolism is in the Izvestia material.

The liver adjusted to the meal time

The researchers studied how the timing of food intake affects the daily metabolic rhythms of the liver. The body constantly adapts its work to what nutrients are available to the body, but this activity changes throughout the day. It is influenced by the molecular circadian mechanism that works in almost all cells of the body, but the intake of food itself is also an important signal for the liver.

The scientists paid special attention to the ACSF3 enzyme, whose activity is associated with mitochondrial metabolism. When the researchers measured its content in the liver, it turned out that it changes throughout the day. At the same time, a change in the time of food availability in mice also led to a change in the circadian rhythm of ACSF3. This suggested that the diet can influence mitochondrial processes through this enzyme.

The work was published in the journal Cell Reports. During the analysis, scientists considered ACSF3 as a possible link between meal timing, protein regulation in mitochondria, and daily metabolic changes in the liver.

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The enzyme linked nutrition to metabolism

To understand the mechanism, scientists have studied a process called lysine malonylation. It is a chemical modification of proteins that can alter their activity. The researchers were interested in how this process is related to mitochondria and liver metabolism and whether it changes during the day.

It turned out that lysine malonylation in mitochondria does indeed follow the circadian rhythm. When the researchers changed the feeding schedule of the mice, this rhythm also changed. The observed changes were related to the activity of ACSF3, which indicated a possible role of the enzyme in transmitting a signal from the diet to the molecular processes inside the liver.

The scientists then reduced the expression of ACSF3 directly in the liver of mice. This allowed us to see what would happen to the metabolism if there were fewer enzymes. The changes affected several metabolic pathways at once, but the most pronounced effects were related to fat metabolism: the role of mitochondria in fatty acid oxidation decreased, lipid synthesis increased, and the circadian rhythms of lipids in the liver changed.

Changes were also observed in glucose metabolism: in animals, the processes associated with the regulation of glucose in the liver and the transmission of insulin signals changed. Thus, ACSF3 turned out to be associated not with one single reaction, but with several processes at once, which must work in concert depending on the availability of nutrients and the time of day.

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Autophagy was activated when the diet was changed.

Another result was a change in autophagy, the process of cellular "recycling" in which the body gets rid of damaged or unnecessary cell components and reuses their parts. When the level of ACSF3 in the liver of mice decreased, the activity of autophagy, on the contrary, increased during the day.

Scientists have not yet determined the exact cause of this reaction. According to one of the proposed versions, increased autophagy may be a compensatory response to metabolic changes that occur with a decrease in ACSF3 activity. The observation also points to a possible link between mitochondrial function, nutrient processing, and cell maintenance mechanisms.

The data obtained allow us to consider the meal time as a separate biological signal. When nutrients enter the body, the liver reacts to them, but the nature of this reaction may depend on the time of day. According to the experimental results, ACSF3 is able to link the food intake signal with the regulation of mitochondrial proteins and the general circadian metabolic system.

At the same time, the researchers emphasize that the work does not allow us to name any specific time of day that is universally useful for eating. The experiments were conducted on mice, so it is not yet possible to say that the discovered mechanism works the same way in humans. The next step should be to study whether ACSF3 and lysine malonylation in the human body react to dietary changes in a similar way and whether prolonged eating disorders can affect the development of metabolic diseases.