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Effects of low carbohydrate and high fat diet associated or not to resistant training on extracellular matrix remodeling and cardiac ventricular fibrosis in rats

Grant number: 19/17737-2
Support type:Scholarships in Brazil - Master
Effective date (Start): July 01, 2020
Effective date (End): June 30, 2021
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal researcher:Heloisa Sobreiro Selistre de Araújo
Grantee:Bianca Caruso Moreira
Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Obesity is an important modifiable risk factor responsible for the development of cardiovascular disease. The heart, as an organ responsible for regulate and supply diverse nutritional and hemodynamic requirements of the body, has several cellular and non-cellular components, which are organized in a three-dimensional network, the cardiac extracellular matrix (CECM). Fibrillar collagen type I and III are the main structural proteins of CECM and provide to the heart the adequate conditions for its functioning. The deposition and removal of collagen fibers are regulated particularly by the activity of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) which, in a balanced manner, prevent collagen fiber deposition at pathological levels in the CECM. The unbalance of this regulatory mechanism may be associated with chronic inflammatory dysfunctions, mainly generated by obesity, which activate signaling pathways that promote pathological remodeling and cardiac fibrosis. Thus, aiming to promote benefits to cardiovascular health, the use of diets like the low carb/high fat (LCHF) approach and physical exercise such as resistance training (RT) has gaining strength and notoriety. However, there is a controversy about the effects of LCHF diet and RT on the promotion of long-term cardiovascular health, considering that the studies did not involve prolonged intervention periods. Therefore, our objective is to study the long-term effects of the LCHF diet, associated or not with RT, on cardiac ventricular tissue remodeling and fibrosis. Thus, we will use an animal model of RT (climb a vertical ladder) and analyze the expression of genes related to collagen synthesis (TGF-²1, CTGF, COL-1 and COL-3), CECM degradation (TIMP- 1, TIMP-2, MMP-2, MMP-9, MMP-13 and MMP-14) and inflammation (TNF-±, IL-6 and 10, IFN-³, MCP-1 and Osteopontin); quantification of enzymatic activity of MMPs by zymography (MMP-2 and MMP-9); western blotting for collagen type I and III and left ventricular morphology of male rats. We believe that our findings may have important clinical implications for the use of LCHF diets and their association with RT in the cardiac ventricle.