Влияние диета-индуцированного и меланокортинового ожирения на экспрессию триптофангидроксилазы 2 в нейронах среднего мозга и гипоталамуса мышей

Abstract

The brain serotonin system plays a key role in the regulation of behavior and cognitive functions, but also in the control of food intake and energy metabolism. This involves the serotonergic midbrain neurons expressing the type 2 tryptophan hydroxylase (TPH-2), which catalyzes the synthesis of serotonin, and the hypothalamic neurons expressing the serotonin receptors. Currently, the changes in the expression and distribution of TPH-2 in midbrain neurons in obesity remain poorly understood. Along with this, it is assumed that serotonin can also be synthesized in the hypothalamic neurons, affecting the serotonin system within the hypothalamus, but there are no data on the expression and possible localization of TPH-2 in the hypothalamic neurons. The aim of the work was to study the TPH-2 expression in the midbrain and its distribution in the neurons of the arcuate, paraventricular and supraoptic nuclei of the hypothalamus in mice with diet-induced obesity (DIO) and in agouti mice with genetically-induced obesity of the melanocortin type. The TPH-2 gene expression was detected in the hypothalamus of C57Bl/6J mice, and the double immunolabeling showed the localization of this enzyme in proopiomelanocortin (POMC) -immunopositive neurons and paraventricular of the arcuate nuclei and in vasopressin-immunopositive neurons of the paraventricular and supraoptic nucleus. In both types of obesity, the number of TPH-2-immunopositive granules in the POMC- and vasopressin-immunopositive neurons was increased, although the expression of the Tph2 gene was increased only in agouti mice. In the midbrain of DIO mice, the content of TPH-2 was decreased, while in agouti mice it did not change. These results indicate the important role of serotonin synthesized in the hypothalamus, which, together with serotonin coming from the midbrain, is involved in the compensatory changes of hypothalamic signaling in obesity. The detection of TPH-2-immunopositive hypothalamic neurons of different types, capable of synthesizing serotonin, indicates the existence of new mechanisms of the autocrine and paracrine serotonin regulation in the hypothalamus, including the obesity conditions.