Role of STAT3 in SF1 neurons of hypothalamus in the effects of leptin in the energy homeostasis

• Grant number: 14/08592-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2014
• End date: June 30, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Lucila Leico Kagohara Elias
• Grantee: Gabriel Henrique Marques Gonçalves
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

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