Favorable Prognostics of Post-Exercise Irisine Released as Prophylaxis of Serious Covid-19 in Obese Elderly

Abstract

Studies sought epidemiological profiles to establish risk groups for Covid-19’s evolution and discovered that the age group above 65 years old is one of the most severely affected, due to the presence of other comorbidities. In the USA approximately 55 million individuals are above that age range and more than 23 million are elderly obese individuals, alongside the high mortality rate in this population and lack of proven effective medicine against Covid-19, therapeutic alternatives against this disease are sought. With the occurrence of inflammatory pulmonary conditions increased by SARS-Cov-2 infection, irisin was indicated as having a potential preventive action. This peptide is secreted endogenously by striated skeletal muscles with fibronectin type III domain-containing protein 5 (FNDC5) proteolysis, when preceded by continued exercise of low to moderate intensity for more than 20 uninterrupted minutes. Regarding the weight variant, previous studies showed low levels of FNDC5 in people with excess fatty acids (in humans, adipose tissue divides into white, favoring the deposit of lipids, triglycerides and fat, more easily inflamed, and brown that stimulates thermogenesis). Among other functions, FNDC5 also stimulates the coactivator 1-alpha of PPAR gamma (PGC-1α) which corroborates with the uncoupling between the Uncoupling Protein 1 (UCP1) and the mitochondria. When UCP1 is disincorporated from this organelle, it becomes active and inhibits ATP synthesis, releasing heat, as well as favoring fatty acid oxidation and provides the mechanism of browning of white fat. After this conversion, irisin reduces ¼ of lipid accumulation present in the adipocyte by lipolysis, significantly increasing the levels of serum triglycerides and glycerols, as well as considerably reducing oxidative stress and DNA damage. Other genes expressed by irisin also assist in the fat browning process, such as TMEM26, ELOVL3, CIDEa and COX7a. Regarding the age variant, the SARS-CoV-2 Spike protein benefits from the high concentration of angiotensin-converting enzyme 2 (ACE2) receptors, present in elderly pulmonary alveoli, which bind to the airway and enable contagion. However, ACE2 is negatively regulated by Tribbles homolog 3 (TRIB3) protein from its connection to the nucleocapsid protein of the virus, generating some protection for the individual when TRIB3 is at satisfactory levels. In elderly men, this protein is below normal levels, making this population more vulnerable to SARS-CoV-2 infection. Moreover, it was verified that irisin’s weekly synthesis promoted by regular physical exercises triples TRIB3 levels in pulmonary alveoli. In short, this hormone was able to negatively modulate two important risk factors related to the inflammatory profile of this elderly population (weight and age), and thus irisin should be considered a potential molecule in the prevention against Covid-19.