PI3K role in the effects of estradiol on SF-1 neurons in the control of energy homeostasis

• Grant number: 20/07368-7
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): June 01, 2021
• Effective date (End): April 30, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal researcher: Lucila Leico Kagohara Elias
• Grantee: Aline Alves de Jesus
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Obesity occurs due to an imbalance between food intake and caloric expenditure and affects millions of people around the world, being linked to an increased risk for heart disease, Diabetes Mellitus and metabolic syndrome. Women at the end of their reproductive life (menopause) are at higher risk of developing Obesity when compared to men. Several studies have shown that this event occurs due to the decrease in menopause, the production of ovarian hormone 17² estradiol (E2) that plays an important role in energy homeostasis. The hypothalamus, considered the main regulator for promoting the homeostasis of the organism in the Central Nervous System (CNS), receives hormonal signals such as E2 and nutrients from the peripheral system that act in populations of arched nucleus (ARC) neurons, which express pro- opiomelanocortin (POMC) and Cocaine and Amphetamine-Regulated Transcript (CART), neuropeptides that promote anorectic effects (reduce food intake and induce satiety), and another population of neurons that express neuropeptide Y (NPY) and Agouti protein (AgRP), orexigenic neuropeptides (stimulate appetite). The stimulation of POMC neurons induces neuronal firing for second order nucleus neurons, such as the SF-1 neurons of the ventromedial hypothalamic nucleus (VMH), which increase the sympathetic activity for white adipose tissue (TAB) and brown adipose tissue ( TAM), inducing the process of thermogenesis, which contributes to the reduction of body weight, by increasing energy expenditure. These effects of the VMH SF-1 neurons are, at least in part, mediated via the PI3K pathway. In addition, VMH has a high expression of the ±2 type E2 receptor (ER±), which has already been shown to be important for the anti-obesogenic effects exerted by the ovarian hormone, however there are few studies that show which intracellular signaling pathway is involved. on the effects of E2 on VMH SF-1 neurons, on the induction of thermogenesis. Thus, the present project aims to evaluate the participation of phosphatidyl inositol kinase 3 (PI3K) signaling in the effects of E2 on VMH SF-1 neurons in energy homeostasis. (AU)