Cardioprotection in Diabetes mediated by aerobic physical training and the role of brown adipose tissue

Abstract

The development of cardiomyopathy in diabetics can lead to an unfavorable clinical outcome, and due to the high prevalence, the search for understanding the pathophysiology and forms of prevention and treatment are increasing in the literature. Key factors such as cardiomyocyte metabolic imbalance, lipotoxicity, fibrosis and cardiac hypertrophy mediate cardiac damage, and part of the mechanisms may be related to the remote action of adipose tissue. While the excess of white adipose tissue is associated with cardiovascular disease and comorbidities, brown adipose tissue (BAT) can improve cardiovascular health via increased substrate oxidation and endocrine action. One of the proteins secreted by BAT with the greatest cardioprotective property is the fibroblast growth factor 21 (FGF-21). Among the strategies to combat cardiometabolic diseases, aerobic physical training (APT) has been shown to be effective in inducing beneficial adaptations in energy metabolism, in the heart and in adipose tissue. In addition, it is known that APT increases the production of FGF-21, as well as its FGFR1 receptor and the ²-Klotho transmembrane protein. Knowing that maintaining BAT functionality is important for metabolic and cardiovascular health, investigating the relationship between BAT and diabetic cardioprotection through APT, as well as the participation of FGF21, can answer a knowledge gap that still exists in the literature. Thus, the present project aims to test the hypothesis that BAT participates in APT-induced cardioprotection in diabetic animals, and that this response is associated with increased levels of FGF21 and FGFR1/²-klotho. (AU)