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

• Grant number: 14/17248-8
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2015
• End date: August 31, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Lucila Leico Kagohara Elias
• Grantee: Lucila Leico Kagohara Elias
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant(s): 16/50015-2 - Development of mouse models using CRISPR-Cas9 technology, AP.R SPRINT

Abstract

The leptin, an adipocyte-derived hormone, and estradiol , , play an important role in the control of energy homeostasis. Through their actions in the central nervous system (CNS), more specifically in the hypothalamus, leptin promotes a state of negative energy balance (decreased food intake and increased energy expenditure). Many of these actions of leptin are mediated by the activation of the STAT3 and ERK signaling pathway in hypothalamic neurons. Of the many neuronal nuclei that express leptin receptors (LepRs) and estradiol receptor (ER), the ventromedial nucleus of the hypothalamus (VMH) is already known to mediate some effects of leptin and estradiol in the energy balance. Studies have shown that the specific deletion of LepRs in this hypothalamic area in mice causes an increase in the body weight and induces obesity by high fat diet (HFD) challenge. However, although the VMH role in mediate the anorexigenic and body weight reduction effects of leptin is already very well determined, little is known about the intracellular mechanisms which leptin activates to mediates its effects in this hypothalamic area. This project aims to evaluate the role of the STAT3 and ERK signaling in mediate the leptin and estradiol effects in the energy balance via VMH. To accomplish that, using cre-lox technology, we will generate mice that do not express STAT3 or ERK only in neurons that express the steroidogenic fator 1 (SF1) in the VMH and, then, we will evaluate the effects of STAT3 or ERK disruption in energy and glucose homeostasis in mice. We will also evaluate leptin sensitivity and its effects on body weight and food intake after chronic leptin infusion. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GONCALVES, GABRIEL HENRIQUE MARQUES; TRISTAO, SABRINA MARA; VOLPI, RAFAELLA EDUARDA; ALMEIDA-PEREIRA, GISLAINE; DE CARVALHO BORGES, BEATRIZ; DONATO, JR., JOSE; DE CASTRO, MARGARET; ANTUNES-RODRIGUES, JOSE; ELIAS, LUCILA LEICO KAGOHARA. STAT3 but Not ERK2 Is a Crucial Mediator Against Diet-Induced Obesity via VMH Neurons. Diabetes, v. 70, n. 7, p. 1498-1507, JUL 2021. (14/17248-8, 18/10090-0, 13/09799-1)