Harmful chromosome

The X chromosome increased the chances of mice having atherosclerosis

It enhances the breakdown and absorption of fats in the intestine, regardless of sex hormones

Polina Loseva, "The Attic"

Female sex hormones reduce the risk of cardiovascular diseases, in particular, atherosclerosis. But after the onset of menopause, when their production is significantly reduced, women not only catch up with men in the frequency of these diseases, but also outstrip them. In search of the causes of this injustice, American researchers studied the effect of sex hormones and sex chromosomes separately on the body of mice. It turned out that the second X chromosome causes the intestines to absorb more fat and puts older females in a less advantageous position than males.

One of the main risk factors for atherosclerosis, doctors consider an increased concentration of cholesterol and other lipids in the blood. In young women, atherosclerosis — the deposition of fat in the vascular wall — and related diseases of the cardiovascular system are less common than in men, probably due to the action of estrogen hormones. But in old age, their concentration decreases, and atherosclerosis develops even more often in women than in men. This allowed a group of American researchers to assume that in addition to sex hormones, some unknown factor is also responsible for the amount of lipids in the blood, but also related to gender.

To test their hypothesis, they used the method of four basic genotypes. To do this, scientists created four groups of mice with a different combination of sex chromosomes and sex glands: XX + ovaries, XY + testes, XY + ovaries, XX + testes. At the same time, as part of the experiment, scientists considered mice to have testes, and girls to have ovaries, without taking into account differences in the set of chromosomes.

To begin with, they were fed a high-calorie ("Western") diet and their body weight was assessed. It turned out that XX mice gained more weight, including adipose tissue, than XY mice, and the effect was more noticeable in male mice. After 4 months of the diet, cholesterol concentrations in the blood were higher in XX-than in XY-mice.

Mice participating in the experiment (left) and their adipose tissue (right). Figures from the article by AlSiraj et al. XX sex chromosome complement promotes atherosclerosis in mice, published in the journal Nature Communications.

To separate the influence of sex chromosomes from the sex glands, scientists also used castrated mice. However, in them, regardless of what sex they were before the removal of glands, genotype XX was associated with an increased level of lipids.

Lipid levels in mice with XX-chromosome (left) and XY-chromosome (right).

The researchers then calculated the surface area of the aorta covered with fat deposits. In females-XX, the percentage of atherosclerosis was higher than in females-XY, and in males XX and XY was approximately the same. But after castration, the ratios changed: in the absence of sex hormones, males and females with genotype XX had much more fat in the aorta, which confirmed the hypothesis of scientists about the influence of sex chromosomes.

The amount of fat in the aorta of mice of each group.

The authors of the article suggested that excess fat can be produced by the liver of XX-animals. However, in liver cells, they found increased activity of genes associated with the immune system, but not with cholesterol synthesis. Then the scientists turned their attention to the intestines. Already in the cells of the intestinal wall of XX-animals, they revealed a high expression of genes that are responsible for the breakdown and absorption of fats.

Interestingly, these genes are located on non-sex chromosomes, which means they are a target for some regulatory genes from the X chromosome. Based on this, the researchers concluded that the X chromosome enhances the absorption of fats from food. This can be useful for the body of a young woman who is preparing for reproduction.

But if in the reproductive period the effect of a large amount of fat is leveled by sex hormones, then after menopause they disappear, and the X chromosome continues to work, provoking the development of atherosclerosis. However, whether sex chromosomes act in a similar way in humans, scientists have yet to confirm.

Portal "Eternal youth" http://vechnayamolodost.ru