Орексин-А и его рецепторы в гипоталамусе мышей с диета-индуцированным и меланокортиновым ожирением

Abstract

Orexin-A is one of the regulators of food intake and energy metabolism. In the brain, this peptide is formed in the neurons of the perifornical hypothalamic area from prepro-orexin, and its action is realized through two types of orexin receptors (OX1R, OX2R). In the diet-induced obesity (DIO), the activity of the hypothalamic orexin system changes, but the data on the orexin-А level and the expression of OX1R and OX2R are few and contradictory. In the case of melanocortin obesity, these data are not available. The aim of the work was to study the orexinergic system in the hypothalamus of mice with the different forms of obesity: with DIO, induced by a high-calorie diet (8 and 16 weeks) in C57Bl/6J (a/a) mice, and agouti mice, C57Bl/6J (Ay/a), with genetically determined melanocortin obesity. The level of orexin-A in neurons was evaluated in brain sections by immunohistochemistry; the gene expression of prepro-orexin (pOx), Ox1r and Ox2r in the hypothalamus was measured by quantitative PCR. In DIO mice, the level of orexin-A and the expression of the pOx and Ox1r genes in the hypothalamus were changed depending on the duration of the diet: increased after 8 weeks and returned to the control values after 16 weeks. At the same time, the expression of the Ox2r gene did not change. In agouti mice, a decrease in the immunopositive orexin-A level in the perifornical area neurons of the hypothalamus was shown. The expression of the pOx, Ox1r and Ox2r genes in the hypothalamus of agouti mice did not change significantly. The findings suggest that reducing orexin-A level in conditions of prolonged, heavy obesity may be a compensatory response aimed at reducing calorie intake, and the orexin system of the hypothalamus can be considered as one of the targets for correcting and preventing the different forms of obesity.