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| Author(s): |
Camila Ideli Morales Fenero
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2020-12-08 |
| Examining board members: |
Niels Olsen Saraiva Câmara;
Luis Fernando Fernandes Marins;
Eliana Faquim de Lima Mauro;
Luis David Solis Murgas
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| Advisor: | Niels Olsen Saraiva Câmara |
| Abstract | |
The consumption of diets rich in fats and carbohydrates, and a sedentary lifestyle are factors that can lead to the development of obesity. Obesity is characterized by excessive accumulation of body fat and is associated with a state of low-grade chronic inflammation, with the participation of inflammatory infiltrate in adipose tissue and systemic release of pro- inflammatory cytokines. The microbiota has been identified as one of the main factors in the pathogenesis of obesity, since germ-free (GF) animals have less capacity to capture energy in the intestine than conventional animals (CV), participating in the induction of weight gain. The dysbiosis generated during obesity is linked to the increased permeabilization of the intestinal wall, leading to a greater influx of lipopolysaccharide (LPS) in the blood, causing endotoxemia and systemic inflammation. The zebrafish emerges as an interesting model for the study of immuno-metabolic and microbiota diseases, due to its small size and easy manipulation, ability to generate germ-free animals and metabolic response similar to that of mammals. Thus, we propose the hypothesis that the microbiota of animals subject to a high-fat diet is necessary to induce low-grade inflammation in these animals. In this study, we established a new model of weight gain by feeding zebrafish adults with a homemade high-fat diet. The impact of the microbiota on low-grade inflammation was analyzed in these animals. At the end of a 6-week period, we observed a significant increase in weight in animals with a high fat diet (HFD) compared to animals in the control group (normal diet - ND), as well as higher basal glycemia, accumulation of lipids in the liver and increased visceral and subcutaneous fat, as well as increased triglycerides and cholesterol values. The HFD group showed an increase in the infiltration of immune cells in the intestine and an increase in inflammatory cytokines compared to ND. HFD myd88-/- animals showed greater weight gain than wild-type animals. HFD fish showed decreased genes of tight junctions proteins, bacterial translocation in the intestine and intestinal dysbiosis with increased Firmicutes. <i>In silico</i> analysis indicated activation of the HIF pathway induced by the microbiota, which was also increased in HFD animals. In conclusion, the administration of a hyperlipidic diet for 6 weeks reproduces a model of weight gain in zebrafish with characteristics of metabolic syndrome, low grade inflammation and dysbiosis of the intestinal microbiota with activation of the HIF pathway in the intestines of HFD animals. (AU) | |
| FAPESP's process: | 15/21644-9 - Obesity-induced inflammation, alterations in the microbiota and their effects on the enteric nervous system: study in an experimental model of zebrafish. |
| Grantee: | Camila Idelí Morales Fénero |
| Support Opportunities: | Scholarships in Brazil - Doctorate |