Irisin modulates genes associated with severe coronavirus disease (COVID-19) outcome in human subcutaneous adipocytes cell culture

• Published in: Molecular and cellular endocrinology Vol. 515; p. 110917
• Main Authors: de Oliveira, Miriane, De Sibio, Maria Teresa, Mathias, Lucas Solla, Rodrigues, Bruna Moretto, Sakalem, Marna Eliana, Nogueira, Célia Regina
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 15.09.2020
• Subjects: ADAM10; ADAM10 Protein - genetics; ADAM10 Protein - metabolism; adipocytes; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Adipose tissue; Amyloid Precursor Protein Secretases - genetics; Amyloid Precursor Protein Secretases - metabolism; Angiotensin-Converting Enzyme 2; Betacoronavirus - genetics; Betacoronavirus - metabolism; cell culture; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cells, Cultured; Coronavirus Infections - virology; COVID-19; COVID-19 infection; endocrinology; Fibronectins - genetics; Fibronectins - metabolism; Fibronectins - pharmacology; FURIN; Furin - genetics; Furin - metabolism; Gene Expression Regulation - drug effects; Gene Ontology; Histone Acetyltransferases - genetics; Histone Acetyltransferases - metabolism; Histone Deacetylase 2 - genetics; Histone Deacetylase 2 - metabolism; Humans; Irisin; Jumonji Domain-Containing Histone Demethylases - genetics; Jumonji Domain-Containing Histone Demethylases - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Models, Biological; Molecular Sequence Annotation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; obesity; Obesity - virology; Pandemics; peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Pneumonia, Viral - virology; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; rab1 GTP-Binding Proteins - genetics; rab1 GTP-Binding Proteins - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; SARS-CoV-2; sequence analysis; Severe acute respiratory syndrome coronavirus 2; Signal Transduction; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; therapeutics; Toll-Like Receptor 3 - genetics; Toll-Like Receptor 3 - metabolism; TRIB3; virus replication; Irisin; ADAM10; SARS-CoV-2; TRIB3; FURIN; Adipose tissue
• DOI: 10.1016/j.mce.2020.110917
• ISSN: 0303-7207; 1872-8057

Obesity patients are more susceptible to develop COVID-19 severe outcome due to the role of angiotensin-converting enzyme 2 (ACE2) in the viral infection. ACE2 is regulated in the human cells by different genes associated with increased (TLR3, HAT1, HDAC2, KDM5B, SIRT1, RAB1A, FURIN and ADAM10) or decreased (TRIB3) virus replication. RNA-seq data revealed 14857 genes expressed in human subcutaneous adipocytes, including genes mentioned above. Irisin treatment increased by 3-fold the levels of TRIB3 transcript and decreased the levels of other genes. The decrease in FURIN and ADAM10 expression enriched diverse biological processes, including extracellular structure organization. Our results, in human subcutaneous adipocytes cell culture, indicate a positive effect of irisin on the expression of multiple genes related to viral infection by SARS-CoV-2; furthermore, translatable for other tissues and organs targeted by the novel coronavirus and present, thus, promising approaches for the treatment of COVID-19 infection as therapeutic strategy to decrease ACE2 regulatory genes. •Positive effect of irisin on the expression of multiple genes related to viral infection by SARS-CoV-2.•FURIN and ADAM10, associated with increased SARS-CoV-2 replication, are diminished by irisin in human subcutaneous adipocytes.•TRIB3, associated with decreases SARS-CoV-2 replication, is increased by irisin in human subcutaneous adipocytes.