Evaluation of the temporal progression of the installation of inflammation, endoplasmic reticulum stress and mitochondrial dysfunction in the hypothalamus of mice subjected to a high fat diet

• Grant number: 13/26319-3
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): April 01, 2014
• Effective date (End): January 31, 2016
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Licio Augusto Velloso
• Grantee: Rodrigo Scarpari Carraro
• Host 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

In several experimental models of obesity is observed a progressive loss of the ability of the hypothalamus in maintaining energy homeostasis. This is due to the fact that neurons in the medial-basal hypothalamus develop resistance to main controlling factors of hunger and thermogenesis, leptin being the most important of them. Studies conducted in the past decade have elucidated some of the mechanisms responsible for induction of leptin resistance in the hypothalamus in obesity. Long chain saturated fatty acids in the diet induces a precocious inflammatory response in the hypothalamus that activates TLR4 receptors and induce the endoplasmic reticulum stress. Recent studies also showed mitochondrial dysfunction as a precocious component during installation of hypothalamic dysfunction. The hypothalamic expression of inflammatory cytokines is already detected 24 hours after the start of the consumption of a diet rich in saturated fatty acids. However, there is no study has comparatively evaluated the temporal evolution of the installation of these three mechanisms described as inducers of this disorder yet, which are: inflammation, endoplasmic reticulum stress and mitochondrial dysfunction. Our hypothesis is that the inflammation precedes and plays a determining role in the development of both the endoplasmic reticulum stress and the mitochondrial dysfunction. The objective of this project is to conduct a study of temporal assessment of the installation of these three biological phenomena during the exposure to a diet rich in saturated fatty acids. In our opinion, the identification of the first mechanisms leading to the development of hypothalamic dysfunction in obesity should help the development of more effective preventive approaches for this disease.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CARRARO, Rodrigo Scarpari. Inflammation precedes endoplasmic reticulum stress and mitochondrial dysfunction in the hypothalamus during the initial stages of obesity progression. 2016. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.