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Evaluation of the anti-inflammatory potential of omega-3 fatty acids through its GPR120 receptor, on the pulmonary parenchyma of obese and diabetic type 2 mice, induced by high-fat diet

Grant number: 17/18665-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2018
Effective date (End): August 31, 2021
Field of knowledge:Health Sciences - Nutrition
Principal Investigator:Dennys Esper Corrêa Cintra
Grantee:Camila de Oliveira Ramos
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

The relationship between the trinomial obesity-asthma-diabetes has increasingly been evidenced by clinical studies. Certainly, it happens due to the pandemic evolution and uncontrolled increasing of obesity worldwide, however, without a clear explanation of the underlying mechanism. Chronic and low-grade inflammation is one of the common denominators present in the genesis of the triad along with insulin resistance and leptin. In the case of type 2 diabetes (DM2) concomitant to obesity, hyperinsulinemia and hyperleptinemia together with molecules such as TNFa, IL1b, IL6, INFg, IL17 also interfere with the pulmonary parenchyma, precipitating the asthmatic genesis. Macrophages infiltrated in the tissue together with hyperleptinemia, potentiate the local inflammatory process, while hyperinsulinemia reduces contractility and dilatation of the organ, although with no defined mechanisms. On the other hand, omega-3 fatty acids (n3) act by reducing systemic inflammatory tone, improving insulin and leptin resistance in various tissues. Several studies have related the benefits of these fatty acids in the pathophysiology of lung disease by inducing bronchial epithelial cell proliferation, reducing inflammation and accelerating the recovery of airways damaged by external stimuli, however, with the mechanics poorly investigated. The purpose of this project is to evaluate the role of the GPR120 protein, a newly described n3 receptor, in the inflammatory lung outcomes of obese and DM2 animals induced by a diet rich in saturated fat. In addition to GPR120, its b-arrestin coupling protein participates, that corroborates part of the disarticulation of the inflammatory process by interfering with the triggering of Toll-like and TNF receptors, as well as the dismantling of the inflammatory structure. Studies with molecules isolated from n3 present contradictory results, probably due to the dose. However, this work intends to investigate the wide molecular orchestration involved in the phenomenon, by offering n3 directly through its exuberant food source (52-58%), namely, flaxseed oil. The experimental design proposed by this project comes very close to human reality, regarding quantity compatible with food consumption, accessibility and reduced chance of fraud in this product, compared to fish oils. Studies show that n3 present in flax (C18:3) exhibits similar binding capacity to GPR120 compared to those from marine sources, EPA (C20: 5) and DHA (C22:6).