Hunger is good for the intestines

Short-term fasting improved the small intestine of mice

Ekaterina Rusakova, N+1

Researchers have found that short-term (during the day) fasting improves the condition of the small intestine in young and elderly mice. As the authors write in Cell Stem Cell, during fasting, the stem cells of the mucous membrane switch from glucose breakdown to fatty acid utilization and this improves the functioning of stem cells and regeneration of the intestinal epithelium.

In the small intestine, which is located between the stomach and colon, there is a partial digestion of food and absorption of the products of digestion into the lymphatic and blood vessels. The mucous membrane of the small intestine consists of numerous villi, circular folds and intestinal glands or crypts, which multiply the absorption surface. In crypts — tiny depressions in the mucous membrane — there are, among other things, stem cells, from which mature cells with different "specialization" develop. Previously, scientists have shown that the diet affects the functions of small intestine stem cells (SCTC). Thus, calorie restriction in the diet increases their number, and a high-fat diet worsens the functioning of stem cells, and the resulting mature cells form tumors more easily.

With aging in multicellular organisms, the number of SCTC decreases and their functions deteriorate. Thus, it is known that in drosophila flies, the deterioration of the SCTC affects the occurrence of epithelial dysfunction. In aging mammals , the activity of SCTC decreases and their ability to recover after radiation exposure. But until now it was unknown how the old SCTCS react to starvation.

American, Belgian and Finnish biologists led by David Sabatini and Emir Yilmaz from MIT decided to look at how the SCTCS of young and old mice adapt to short-term fasting, which lasts 24 hours.

First, the researchers evaluated the ability of stem cells to produce so-called "mini—intestines" - self-renewing cellular organelles, from which different types of mature cells can later develop. It turned out that this ability in the stem cells of starved mice is higher than in animals from the control group.

The stem cells of mice that starved during the day (right) form much larger organoids than the cells of mice in the control group. Figure from the MIT press release Fasting boosts stem cells’ regenerative capacity – VM.

To find out how fasting increases the activity of SCTC, the authors of the article analyzed transcriptomes of stem cells isolated from the small intestine of starved and fed mice. Transcriptome analysis allows you to look at the activity of genes and understand which proteins were synthesized in cells.

It turned out that the stem cells of starving mice switched from splitting carbohydrates to beta-oxidation of fatty acids (this is one of the ways to obtain ATP — a substance that takes part in most of the energy processes occurring in cells). Also, in the stem cells of hungry mice, the synthesis of the CPT1A protein involved in the transfer of fatty acids through the mitochondrial membrane increased and the level of free fatty acids increased. The researchers found that a short-term "shutdown" of the CPT1A protein negates the effect of starvation, and its three-month absence leads to a decrease in the number of stem cells and deterioration of the remaining ones.

In conclusion, the authors compared the state of small intestine stem cells in young (3-4 months) and old (17-24 months) mice. It turned out that with age in mice, the number of SCTC decreases by 62 percent compared to young mice, their ability to divide and differentiate into epithelial cells decreases. Also, the stem cells of old mice regenerated worse after radiation exposure.

Then the scientists looked at how the stem cells of young and old animals react to daily starvation. This time, the researchers not only forced the animals to starve, but also initiated the beta-oxidation of fatty acids by pharmacological means. As a result, the activity of stem cells in old mice increased, they began to synthesize more cellular organelles, and their number of stem cells increased. It is worth noting that the number of mature cells increased slightly (in the case of pharmacological activation of fatty acid oxidation) and in both cases it was still less than in young animals.

The researchers were unable to give a clear answer as to how the oxidation of fatty acids is associated with an increase in the activity of mouse stem cells. According to a recent study, in the progenitor cells of blood cells, it affected the rate of division in experiments "in vitro". But in living organisms, such a pattern was not revealed. Other work has shown that the limited oxidation of grape acid promotes the growth of stem cells of the small intestine and hair follicles. It is possible that fatty acids have a similar effect on SCTC. This assumption is also confirmed by the fact that aging is accompanied by a deterioration in the metabolism and oxidation of fatty acids in the mitochondria of some tissues.

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