Role of high-fat diets in the gut-microbiota-heart axis: A translational approach based on lipid metabolism, oxidative metabolism and inflammation

• Grant number: 22/09893-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2023
• End date: April 30, 2027
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Nágila Raquel Teixeira Damasceno
• Grantee: Ribanna Aparecida Marques Braga
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiovascular diseases (CVDs) remain the leading cause of death in Brazil and worldwide. Although a large number of studies show a positive relationship between excessive fat intake and CVDs, more recently, hyperlipidic diets have been the focus of popular and scientific interest as a strategy for prevention and management of diseases and risk factors for cardiovascular events. These controversies have required more robust and integrative scientific approaches, and in this context, established markers (lipid, inflammatory and oxidative) have been investigated with newer methods (microbiota and omics strategies). From the point of view of Nutrition, the qualitative aspects of fats have shown superiority to the quantitative ones. In this context, the present study aims to evaluate the role of fatty acid quality in hyperlipidic diets in modulating the gut-microbiota-heart axis through a translational approach. Aiming to identify mechanistic pathways linking the gut-microbiota-heart axis two studies will be conducted. Study 1 will be experimental with 60-day segment, and will consist of 56 male Wistar P40 rats distributed into 6 groups (n=6): group1 - standard chow; group 2 - standard chow for rats with status epilepticus; group 3 - hyperlipidic diet rich in saturated fatty acids; group 4 - d rich in saturated fatty acids hyperlipidic diet rich in saturated fatty acids for rats with status epilepticus; group 5: hyperlipidic diet rich in omega-3 fatty acids; and group 6 - hyperlipidic diet rich in omega-3 fatty acids for rats with status epilepticus. Throughout the follow-up, feed and water consumption; weight gain, length will be monitored. From plasma the following biomarkers will be monitored: Ketone bodies (B-hydroxybutyrate), inflammatory cytokines (IL1 ², IL6, IL8, IFN gamma, TNF-± and anti-inflammatory IL10), assessment of intestinal barrier integrity (LPS, FBAP, lithostamine 1-beta), lipid metabolism markers (total cholesterol, triacylglycerols, HDL-c, LDL-c, non-esterified fatty acids, LDL and HDL subfractions. The heart and intestine will be removed and, after appropriate treatments, the following analyses will be performed: oxidation markers (oxidized low density lipoprotein, antioxidant capacity - Lag time and thiobarbituric acid reactive substances - TBARS), expression of inflammatory cytokines, histomorphometric and immunohistochemical analyses. Furthermore, analysis of the intestinal microbiota in fecal samples will be performed by sequencing the 16S rRNA gene. The translational approach of this study will be based on the baseline cross-section of the Life and Health Cohort in Pomerode - SHIP - BRAZIL conducted in the period 2014 and 2018. Socioeconomic and demographic data, lifestyle, clinical aspects, examination of subclinical atherosclerosis, nutritional and dietary status will be used. From these parameters cardiovascular risk will be estimated using the predictive equation proposed by the ACC/AHA. Based on the plasma and fecal samples collected, the same biochemical parameters analyzed in Study 1 will be evaluated. All results obtained in Study 1 and 2 will be analyzed in the SPSS v 23.0 program with a significance level of p<0.05 for all tests.