A study conducted at the Universidade Estadual Paulista (Unesp) suggests that the hormone irisin, which is released by muscles during physical activity, can have a therapeutic effect on Covid-19. When analyzing gene expression data from fat cells, the researchers observed that the substance has a modulating effect on genes that are associated with greater replication of the new coronavirus (SARS-CoV-2) in human cells.
The finding was based on transcriptome data (a set of RNA molecules expressed in a tissue) from fat cells that were not infected with SARS-CoV-2 and received doses of irisin. Transcriptome data to establish correlations.
The result is a positive signal for the search for new therapies in this emergency situation with the pandemic. It should be noted that these are preliminary data, an indication of Irisin̵'s therapeutic potential in cases of Covid-19. We provide a research pathway to prove the beneficial effects of the hormone or not in infected patients, ”says Miriane de Oliveira, researcher at the Unesp School of Medicine in Botucatu (SP).
The article, published in the journal Molecular and Cellular Endocrinology, describes data generated in Oliveira’s postdoctoral study, which analyzed the effects of irisin and thyroid hormones in adipocytes. The work was supported by FAPESP.
Using sequencing techniques, the researchers identified 14,857 genes expressed in a line of subcutaneous adipocytes. When cells were treated with irisin, they observed that the expression of several genes was altered.
Due to the pandemic, the researchers decided to investigate possible effects of irisin on genes related to SARS-CoV-2 replication. At the data cross, they found that irisin treatment in fat cells decreased the expression of the TLR3, HAT1, HDAC2, KDM5B, SIRT1, RAB1A, FURIN and ADAM10 genes, regulators of the ACE2 gene – fundamental to virus replication in human cells. ACE2 codes for the protein that the virus needs to enter human cells.
Another positive aspect of the study was that Irisin tripled the transcription levels of the TRIB3 gene. A previous study showed the importance of maintaining TRIB3 expression. In the elderly, it is common to reduce the expression of this gene, which may be related to the increased replication of SARS-CoV-2 and the increased risk of this population for Covid-19.
“A third important aspect is the discovery of other research groups on adipose tissue, which apparently serves as a repository for the virus. This helps to understand why obese people are at a higher risk of developing the severe form of Covid-19. That being said, obese individuals tend to have lower levels of irisin as well as higher amounts of the virus receptor molecule [ACE2]compared to non-obese people, ”it continues (read more at: agencia.fapesp.br/33612/)
Irisin, which is normally produced endogenously during continuous exercise, is known to function in the metabolic modification of white adipose tissue – which stores triglycerides and lipids, accumulates fat, and can become inflamed – and has a function similar to that of brown adipose tissue. This process favors energy consumption, which makes irisin an endogenous therapeutic for metabolic diseases such as obesity.
The hormone’s capacity to modulate the activity of macrophages (defense cells of the immune system) is also known, which confers potential anti-inflammatory properties.
Oliveira’s study is an example of how managing data from basic research can lead to other discoveries and lines of research.
“We first conducted a comparative analysis between the effects of irisin and thyroid hormones in reducing lipid accumulation and in modulating genes in fat cells. The study generated a huge volume of data, and when the pandemic came and other research groups discovered the genes associated with SARS-CoV-2 replication, we decided to look at our database to see how Irisin works [e os hormônios tireoidianos] could influence the disease ”, reports Agência FAPESP.
The research group’s original investigation sought to find out how these hormones play a thermogenic role in reducing adipose tissue and producing energy in adipocytes. “To do this, we created the transcriptome and identified which genes are affected in the presence of these hormones. Data that served as the basis for the study on Covid-19, ”he says.
With the study, Oliveira identified that irisin not only decreased lipid accumulation, but also increased the expression of uncoupling protein 1 (UCP1), which is associated with higher calorie consumption. The increased expression of this protein is compatible with a reduction in DNA damage and oxidative stress.
With a better understanding of irisin’s role in obesity-related factors, and also its possible relationship with Covid-19 cases, the research group will analyze the effects of the hormone in cells infected with SARS-CoV-2. The work, which is also coordinated by the professor at the Faculty of Medicine of Unesp in Botucatu Célia Regina Nogueira de Camargo, is supported by the Coordination for the Improvement of University Staff (Capes).
“The aim is to take a further step in this study and to verify the results of our bioinformatics work in a three-dimensional model of the adipocyte cell culture. We want to understand how irisinmodulation occurs in the genes associated with replication of the new coronavirus, ”he says.
Maria Fernanda Ziegler | FAPESP agency