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| Author(s): |
Rodrigo Scarpari Carraro
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2016-01-28 |
| Examining board members: |
Licio Augusto Velloso;
Gabriel Forato Anhê;
José Donato Júnior
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| Advisor: | Licio Augusto Velloso |
| Abstract | |
Long-chain saturated fatty acids present in the diet induce a very early inflammatory response in the hypothalamus through the activation of TLR4 and induction of endoplasmic reticulum stress (ER stress). Recent studies have suggested that changes in mitochondrial function could play a pathophysiological role during the installation of obesity-associated hypothalamic dysfunction. In this study we evaluated inflammatory markers, endoplasmic reticulum stress and mitochondrial alterations in the initial stages of diet-induced obesity. Our results showed an early increase in the expression of proteins related to inflammation, IL-1'beta', IL-6, IL-10, TNF-'alfa' and fractalkine in Swiss mice subjected to a diet rich in saturated fat. The exposure of mice to 3 hours fat diet was capable of increasing the content of fractalkine. Six hours dietary exposure to fat resulted in the increase of the chaperone GRP78, which is involved in the unfolded protein response (UPR) in the endoplasmic reticulum. This increase remained steady as far as the high-fat diet was maintained. The ER stress sensor proteins were affected after the induction of the inflammatory response; thus, IRE-1'alfa' and ATF6 increased 3 and 7 days after dietary fat introduction, respectively. Mitofusin 2, which is involved in mitochondrial morphological dynamics, was reduced after 24 hours exposure and increased after 7 days of dietary fat exposure. Because these changes suggest morphological rearrangements of the mitochondria, we next employed electron microscopy and identified changes in contacts between mitochondria and the endoplasmic reticulum. However, exposure to high-fat diet did not alter the mitochondrial respiration as evaluated in hypothalamic explants. Thus, we conclude that the consumption of a high-fat diet induces rapid inflammatory response in the hypothalamus of mice, which is followed by ER stress. Although we detected changes in the expression of at least one protein involved in mitochondrial morphology and dynamics and on the number of contacts between mitochondria and the endoplasmic reticulum this was not accompanied by changes in mitochondrial respiration in the hypothalamus (AU) | |
| FAPESP's process: | 13/26319-3 - 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 |
| Grantee: | Rodrigo Scarpari Carraro |
| Support Opportunities: | Scholarships in Brazil - Master |