Cardioprotection in diabetes mediated by aerobic physical training and association with fibroblast growth factor 21 (FGF21)

• Grant number: 20/12005-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): April 01, 2022
• Effective date (End): February 28, 2026
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Fabiana de Sant'Anna Evangelista
• Grantee: Bruno Vecchiatto
• Host Institution: Escola de Artes, Ciências e Humanidades (EACH). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The development of diabetic cardiomyopathy is a multifactorial process that includes changes in substrate metabolism, increased oxidative stress, inflammation, fibrosis, induction of apoptosis and microvascular disease. Due to the increasing prevalence of diabetes in the population and the negative clinical outcomes for the heart, more and more has been invested in studies aimed at the discovery of cardioprotective strategies. Evidence in the literature revealed that the fibroblast growth factor 21 (FGF-21), a protein with a molecular weight of 23kDa, plays a cardioprotective role and that part of the action is related to the improvement of oxidative metabolism and reduction of cardiac remodeling. Although pharmacological agents are primarily investigated, more and more is known about the efficiency of aerobic physical training (TFA) for the prevention and treatment of cardiometabolic diseases. Considering that metabolic damage and cardiac remodeling may progress to diabetic cardiomyopathy, that FGF21 is associated with cardioprotection and that TFA induces beneficial effects for the heart, the present project aims to evaluate the effect of TFA on oxidative metabolism and cardiac remodeling in an experimental model of diabetes and the association with FGF21. The hypothesis to be tested is that TFA prevents damage to oxidative metabolism and cardiac morphology induced by diabetes and that this response is associated with increased expression of FGF21 and the FGFR1 / 2-klotho receptor.