Role of STAT3 in SF1 neurons of the hypothalamus on the effects of estradiol on energy homeostasis

• Grant number: 24/22685-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Lucila Leico Kagohara Elias
• Grantee: Gabriela Lucas Ferreira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/18071-5 - Hydroelectrolytic and energy homeostasis: from cellular metabolism to endocrine systems in different phases of development, AP.TEM

Abstract

Energy homeostasis involves a complex integration of multiple signals about the body's energy demand. Several hypothalamic regions, such as the paraventricular nucleus (PVN), arcuate nucleus (ARC), ventromedial nucleus (VMH), dorsomedial nucleus (DMH), and lateral hypothalamic area (LHA), are involved in the neural circuit that regulates food intake and are responsible for integrating these signals. These regions, especially the VMH, have neurons that are sensitive to the action of leptin, an adipocyte derived hormone whose actions in controlling food intake and energy expenditure are mediated by its interaction with the LepRb receptor. The STAT3 signaling pathway has been identified in the literature as the major signaling pathway mediating the actions of leptin. The VMH also contains neurons that express SF-1, an essential regulatory transcription factor for development and endocrine function, involved in the activity of genes mainly related to the gonads and adrenal glands. In particular, gonadal hormones play an influential role in food intake and body weight. The role of estradiol in the control of energy homeostasis was initially demonstrated by the increase in food intake and body weight gain after ovariectomy in rats - changes that can be reversed by treatment with estradiol. Although the effects of estradiol on feeding behavior and body weight are well established, the mechanisms underlying these effects on the central nervous system are still unknown. Therefore, this project aims to investigate the relationship between estradiol and the STAT3 signaling pathway in VMH SF-1 neurons in the regulation of energy homeostasis using the CRE-LOX recombination method for specific deletion of STAT3 in SF-1 neurons in ovariectomized females, with and without estradiol replacement.