Intermittent fasting and digestive adaptation surgery: translational assessment of impact of cardiovascular risk factors and atherogenesis

• Grant number: 11/22970-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2012
• End date: March 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Bruno Caramelli
• Grantee: Fernanda Reis de Azevedo
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 10/19827-4 - Intermittent fasting and the digestive adaptation III surgery: translational assessment of its effects on cardiovascular risk factors and atherogenesis, AP.TEM

Abstract

Primary prevention is the most important strategy for controlling pathogenic global burden of cardiovascular disease. In clinical practice, food restriction represents a valuable preventive resource. However, low adherence rates and the abandonment of the diet are major obstacle to treatment. Considering the discovery of new markers and mechanisns relating food restriction to cardiovascular risk factors, it is possible and necessary to seek for efficient alternatives to improve adherence and efficacy in preventive dietetic treatment. Intermittent Fasting (IF) is an option in which individuals are subject to fast every other day. Previous studies reported that adherence to this kind of diet was higher. For more severe cases, refractory to treatment of obesity and its associated comorbidities such as Diabetes type II, there is the alternative of surgery. The technic known as Digestive Adaptations III is directed to this gruop of patients. This surgery changes the intestinal tract by reducing the gastric volume and performing an anastomosis between the ileum and the stomach, creating a bipartition in the intestine. This structural modification promotes satiety and increased insulin sensitivity more intensively than other surgical strategies. The effects of Intermittent fasting and Digetsive Adaptations III Surgery over cardiovascular risk factors and markers related to the development of atherosclerosis are not yet established. Objectives - to investigate mechanims and genetic and molecular bases related to food restriction and its relation with cardiovascular risk factors. Methods - we will carry out an experimental study in a murine model and a clinical trial. In the murine model (mice LDLR-/ -), we will perform genetic analysis through a "genetic screening" followed by confirmation of the groups of genes of interest by RT-PCR and Western blotting, flow cytometric analysis of apoptosis of lymphocytes, monocytes and endothelial progenitor cells, lipid peroxidation rate, aortic vascular reactivity and zymography of metalloproteinases 2 and 9 in addition to insulin, glucose, lipid profile, blood pressure and heart rate. In the clinical trial, besides lipid profile and glucose, the incretin hormones, adipokines will be determine, as well as the amount of epicardial fat before and after surgery. (AU)