Participation of STAT3 in hypothalamus SF1 neurons under the effects of estradiol in energy homeostasis

Abstract

Obesity constitutes an emerging issue for public health due to the high morbidity and mortality associated with this disease, which has presented a substantial increase in its prevalence. The central nervous system is essential to the regulation of energy homeostasis and to the control of food intake as well as body weight. The hypothalamus, centre of convergency and of integration of signals related to the energetic state, contains diverse nuclei, such as the arcuate nucleus (ARC), paraventricular nucleus (PVN), lateral hypothalamic area (HLA), ventromedial nucleus (VMH), and dorsomedial nucleus (DMH). The VMH is an important site of regulation for body weight and for energy homeostasis. In this nucleus, the specific expression for the NR5AI gene, which codifies the SF-1 transcription factor, was described. Data from literature evidenced the crucial participation of VMH neurons that express SF-1 in control of food intake and body weight. The leptin, produced by adipocytes and active in the inhibition of food intake and increase of energetic expenditure, has significant signalling in the VMH when circulating in levels proportional to body adiposity, in addition to regulating the sympathetic tonus to peripheral tissues. The hypothalamic actions of the leptin are meadiated by STAT3. Gonadal hormones also associate themselves with the regulation of food intake and body weight. The estradiol (E2) performs its activity in energy homeostasis through the receptor ERa, whose expression was demonstrated in the VMH. As a result, the present project aims to investigate the involvement of the signalling means of STAT3 in VMH SF-1 neurons in energy homeostasis and its relation to the estradiol activity. To this end, the CRE-LOX methodology will be used for the achievement of specific deletion of STAT3 in SF-1 neurons in ovariectomized females with and without estradiol reposition.