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Chronic insulin receptor blockade in amygdala: effects on energy metabolism

Grant number: 13/22321-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2013
Effective date (End): December 31, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Mario Jose Abdalla Saad
Grantee:Fernanda Machado Chaves
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Obesity is growing exponentially worldwide and is associated with multiple comorbidities. Therefore, the study of the molecular mechanisms related to the development of obesity is extremely relevant today. Most studies focused on the action and insulin signaling in the hypothalamus in the regulation of energy homeostasis. However, insulin has effects on other regions of the nervous system, such as the amygdala. This region includes the dopamine reward system, and metabolic profile, and have been considered as a possible field of regulation of food intake. Thus, the first aim of this study is to investigate whether chronic inhibition of insulin receptor expression by siRNA, specifically changes in the amygdala: body weight, fat mass, food intake, energy expenditure and respiratory quotient. As a complement, the second objective of the study is to investigate whether animals with siRNA have changes in serum insulin, leptin, ghrelin, adiponectin and glucose. Along the same lines, the third objective of the study is to investigate the animals with siRNA exhibit alterations in glucose metabolism and insulin through glucose tolerance test, test of pyruvate and insulin tolerance test. The amygdala is a brain region important for the control of responses to stress and anxiety. These responses are mediated by the release of neuropeptides. The fourth objective of this study is to investigate whether chronic inhibition of expression of the insulin receptor specifically in the amygdala alters the expression of neuropeptides related to energy metabolism as NPY and CRH in this brain region.