Irisin is a hormone secreted from muscles in response to exercise. It can help maintain a healthy weight, slow aging, and improve cognition, among other powerful health benefits. Researchers from São Paulo State University (UNESP) also recently found that irisin modulated genes are linked with replication of the novel Covid-19 in human cells.
ACE-2: How is it linked to coronavirus?
The study, which appeared in the journal Molecular and Cellular Endocrinology, suggests that the irisin hormone could have a therapeutic effect on Covid-19 patients. In the abstract of their study, the team said that obese patients are more susceptible to develop Covid-19 severe outcomes because of the role of ACE-2 called the angiotensin-converting enzyme 2.
In search treatments for Covid-19, many researchers focused their attention on ACE-2 as it is a protein that enables the coronavirus to infect human cells. They said that ACE-2 provides the entry point for the virus to infect and hook into a wide range of cells. Previously, Paul Insel, a Professor of Pharmacology and Medicine from the University of California San Diego and colleagues, highlighted that ACE-2 is present in many tissue and cell types, including the lungs, gastrointestinal tract, liver, kidneys, and blood vessels.
Normally, ACE-2 is critical to regulating processes, such as wound healing, inflammation, and blood pressure. However, not everyone has the same number of ACE-2 on their cells. Their quantity can vary in different cells and tissue and among individuals. Insel and team are not part of the UNESP research.
In the recent study by the UNESP team, they analyzed the transcriptome - set of all RNA transcripts – of adipose cells not infected by Covid-19 and they treated it with irisin. Adipose tissue is specialized in storing energy as fat. The team then compared the data for genes tied to Covid-19 with their transcriptomic data to find a link.
The result shows that irisin treatment increases the levels of gene TRIB3 to 3-fold and decreased the levels of other genes. A previous study demonstrated the significance of maintaining the expression of the TRIB3 gene. Expression of such is even frequently diminished in other people, a finding that could also be linked to a higher risk of Covid-19 and replication of SARS-CoV-2 in said group of population.
The team said that their result provides a clue in the search for the treatment of Covid-19. However, they highlight that their findings merely suggest the therapeutic potential in Covid-19 cases. There needs to be further research to determine whether the effects of irisin on patients with the coronavirus can indeed be beneficial. The team’s data was produced by Miriane de Oliveira, a researcher at UNESP's Medical School, and supported by the São Paulo Research Foundation. It furthermore focused on the action of thyroid and irisin hormones in adipocytes.
The authors used RNA-seq technology, which is a sequencing technology to reveal the quantity and presence of RNA, to identify 14,857 genes that are expressed in human subcutaneous adipocytes. When cells were treated with irisin hormones, the team observed changes in gene expression.
Effects of irisin on genes
The team decided to investigate the possible effects of the exercise hormone on genes because of the pandemic. They also found that irisin treatment reduced the expression of genes, ADAM10, TLR3, RAB1A, FURIN, SIRT1, HDAC2, KDM5B, and HAT1. As a result, it regulates ACE-2.
Another important finding is that adipose tissue seems to serve as a repository for the coronavirus, according to Oliveira. This can help explain why obese people have a higher risk of developing a severe form of Covid-19. People with obesity also tend to have higher levels of the receptor molecule used by ACE-2 and lower levels of irisin compared to non-obese individuals.
According to Worldometer, countries with the highest reported cases of Covid-19 as of September 23 includes USA (7,098,291 total cases), India (5,650,540), Brazil (4,595,335), Russia (1,122,241), and Colombia (777,537).
Irisin is produced endogenously during a continuous exercise and is thought to be involved in the browning of adipose tissue. White adipose tissue (WAT) or white fat is one of the two types of adipose tissue found in mammals, the other is brown adipose tissue. In non-overweight and healthy humans, white adipose comprises as much as 25% of the body weight in women and 20% in men. White fat stores energy in the form of lipids and triglycerides and can be inflamed. On the other hand, brown fat breaks down fat molecules and sugar to create heat and maintain body temperature, as explained by medical research platform Medical Xpress.
In short, the irisin hormone is a part of the calorie-burning process that helps treat obesity and other metabolic disorders. It is believed to control the activity of macrophages, which are important cells of the immune system that are formed in response to an accumulating damaged or dead cell or an infection.
The Brazilian study is an example of how managing information gathered in basic research can serve as the foundation for other research and discoveries. Oliveira told Medical Xpress that they started their research with a comparative analysis of the action of thyroid and irisin hormones in modulating genes in adipose cells and moderating fat accumulation. Then, they were able to produce a large amount of data. The discovery of other research teams of genes linked with the replication of Covid-19 and as the pandemic continues to grow, the Brazilian researchers decided to utilize their database to know how irisin may influence the coronavirus.
Their original investigation started to discover how the thermogenic (tendency to produce heat) role of two hormones in generating energy in adipocytes and reducing adipose tissue.
UN Report shows that when it comes to physical activity, the USA ranks near the bottom, at 143 out of 168 surveyed countries. The least physically active countries include Kuwait as 67% do not meet the minimum suggested guidelines for physical activity, which is 2.5 hours of moderate activity weekly. It is followed by Saudi Arabia (53%), Iraq (52%), Costa Rica (46%), Portugal (43%), and the USA (40%). Meanwhile, ergonomics platform ErgonomicTrends.com shared that sedentary behavior increases the risk of colon cancer by 24%, endometrial cancer by 66%, and lung cancer by 21%.
The UNESP findings do not just provide us an understanding of how irisin hormone modulates genes linked with Covid-19 replication, it also highlights the significance of physical activity and exercise during the pandemic.