Impact of ketogenic diets on cardiac muscle: an experimental and mechanistic approach

• Grant number: 23/17805-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2024
• End date: September 30, 2028
• Field of knowledge: Health Sciences - Nutrition
• Principal Investigator: Nágila Raquel Teixeira Damasceno
• Grantee: Chayane Gomes Marques
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiometabolic diseases, including CVD, are among the main causes of morbidity and mortality in Brazil and worldwide. Diet is one of the main risk behaviors related to these diseases and, therefore, is part of primary prevention measures in national and international guidelines. In recent years, the possibility of clinically implementing the ketogenic diet (KD) as a non-pharmacological strategy in the treatment of some CVDs has been studied. However, there are many gaps and controversies regarding the metabolic, molecular and cellular responses caused by the medium and long-term use of the KD and its variations. Therefore, this study aims to assess the impact of two types of KD at the heart level, in the context of health and disease, using an experimental and mechanistic approach. The study will last 75 days and will consist of 18 male Wistar P40 rats, divided into 3 groups (n=6): Control group, composed of animals that will receive a standard diet (AIN-93); Classic Ketogenic Diet group (CKD, n = 6) which will receive a ketogenic diet containing around 90% lipids, especially saturated fatty acids; Modified Ketogenic Diet group (MKD, n = 6), whose animals will receive a ketogenic diet containing around 90% lipids, mainly MUFAS and PUFAS, being rich in É-3. Monitoring of feed, water consumption, weight gain and length will be carried out throughout the experiment. The following biomarkers will be monitored from the plasma: ketone bodies (²-hydroxybutyrate), inflammatory cytokines (IL1 ², IL6, IL8, IFN gamma, TNF-± and anti-inflammatory IL10), markers of lipid metabolism (total cholesterol, triglycerides , HDL-c, LDL-c, non-esterified fatty acids, LDL and HDL subfractions) and transcription factors (Nrf2 and NF-kB). The heart will be removed and, after appropriate treatments, the following analyses will be carried out: oxidative stress markers (oxidized low-density lipoprotein, antioxidant capacity - Lag time and thiobarbituric acid reactive substances - TBARS), fatty acid oxidation markers (CPT1a, CPT2, HMGCS2, OXCT1, PPAR-³1 and UCP3), expression of inflammatory cytokines, histomorphometric and immunohistochemical analyses. The results obtained will be analyzed using the SPSS v 23.0 program and p values < 0.05 will be noted as significant.