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Modulation of hypothalamic autophagy in hypothalamus of mice fed with high-fat diet

Author(s):
Mariana Portovedo de Oliveira Araújo
Total Authors: 1
Document type: Master's Dissertation
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
Defense date:
Examining board members:
Pratícia de Oliveira Prada; Vanessa Arantes
Advisor: Marciane Milanski Ferreira
Abstract

The mediobasal hypothalamus is known as the primary site which coordinates the balance between food ingestion and energy expenditure. In this context, diets with high content of saturated fatty acids are pointed as the main diet factor responsible for the development of obesity. Recent data have shown that autophagy, a process which regulates cellular homeostasis by degrading dysfunctional proteins and organelles, is crucial to maintain the functionality of hypothalamic AgRP and POMC neurons, which in turn are responsible for coordinate body energy homeostasis. In this study we evaluated the hypothalamic distribution and content of autophagy’s machinery proteins in an animal model of diet-induced obesity at 8 or 16 weeks of high-fat diet and in response to intracerebroventricular injections of a saturated fatty acid. We demonstrate that chronic exposure to a high-fat diet can lead to an increased expression of inflammatory markers and downregulation of autophagy. Also, intracerebroventricular treatment with stearic acid appears to contribute to the decrease of hypothalamic autophagy, suggesting that saturated fatty acids can contribute to the downregulation of autophagy found in obese mice. Finally, induction of autophagy in obese mice with rapamycin was able to improved glucose homeostasis and reverse inflammatory and apoptosis markers, the main mechanisms involving dysregulation of energy balance related to hypothalamic neurons, while no weight loss was observed during the treatment. Understanding the cellular and molecular mechanisms of these processes is crucial for identifying new therapeutic targets for obesity. (AU)

FAPESP's process: 11/14565-4 - Characterization of autophagy in the hypothalamus of different animal models of obesity
Grantee:Mariana Portovedo de Oliveira Araújo
Support type: Scholarships in Brazil - Master