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Role of STAT3 and PI3K signaling in SF1 neurons of the hypothalamus on energy homeostasis

Grant number: 18/10090-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2018
Effective date (End): February 28, 2019
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Margaret de Castro
Grantee:Gabriel Henrique Marques Gonçalves
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The leptin, an adipocyte-derived hormone, plays an important role in the control of energy homeostasis. Through its 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 signaling pathway in hypothalamic neurons. Of the many neuronal nuclei that express leptin receptors (LepRs), the ventromedial nucleus of the hypothalamus (VMH) is 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 the body weight and induces Obesity by High Fat Diet (HFD) challenge. However, although the role of VMH in mediating the anorexigenic and body weight reduction effects of leptin is very well determined, little is known about the intracellular mechanisms which leptin activates to mediate its effects in this hypothalamic area. Previous data have shown that both STAT3 and PI3K signalling pathways are crucial to protect against Obesity induced by high fat diet possible by diferent mechanisms: the first by reducing food intake and the second by increasing energy expenditure. To test this hypothesis, this project aims to evaluate the effect of the deletion of both signalling pathways in the VMH through generation of mice with specific deletion of STAT3 and PI3K in SF1 neurons and, then, we will evaluate the effects of disruption of these pathways on energy homeostasis with regular chow diet and HFD. (AU)