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Hypothalamic autophagy evaluation in response to treatment with saturated fatty acid in vitro and in vivo: connections with inflammatory pathways

Grant number: 15/25710-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2016
Effective date (End): August 31, 2019
Field of knowledge:Health Sciences - Nutrition
Principal Investigator:Marciane Milanski Ferreira
Grantee:Andressa Reginato
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID
Associated scholarship(s):17/08151-9 - Neuronal autophagy in response to palmitate treatment: crosstalk with microglial cells, BE.EP.DR

Abstract

Obesity is a disease characterized by excess body fat that compromises health and has become a global public health problem in developed and in the development countries. One of the main aspects related to obesity is the presence of chronic low-grade inflammation that culminates in many disorders, including the loss of control on food intake by a small region of the central nervous system, the hypothalamus. Part of the inflammatory signaling is due to activation of TLR4 (Toll like receptor 4) in the hypothalamus as a consequence of excess fatty acids, especially saturated, that is generally ingested in obesity. Recent studies showed the role of autophagy in the control of energy balance exercised by the hypothalamus. Autophagy is defined as a powerful process of lysosomal degradation which maintains cell viability by degrades organelles and senescent protein aggregates. Changes in the activity of autophagy appear to disrupt the hypothalamic homeostasis. However, the molecular mechanisms involved in the failure of autophagy in hypothalamic neurons in response to high fat diet-induced obesity are not yet known. Therefore, the aim of this study is to investigate the relationship between activation of inflammatory pathways including TLR4 activation and autophagy pathway in the hypothalamus of experimental animals and cell lines. For this, we will use lines of neuronal cells and microglia treated with addition of fatty acids and mice swiss lineage fed for different times with high fat diet rich in saturated fatty acid to elucidate the connection between these processes and potential therapeutic targets for the treatment of obesity.