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

Mol Cell Endocrinol. 2020 Sep 15:515:110917. doi: 10.1016/j.mce.2020.110917. Epub 2020 Jun 25.

Abstract

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.

Keywords: ADAM10; Adipose tissue; FURIN; Irisin; SARS-CoV-2; TRIB3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM10 Protein / genetics
  • ADAM10 Protein / metabolism
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism
  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / genetics
  • Betacoronavirus / metabolism
  • COVID-19
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cells, Cultured
  • Coronavirus Infections / virology
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Fibronectins / pharmacology*
  • 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
  • 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 / virology
  • Pandemics
  • 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
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • SARS-CoV-2
  • Signal Transduction
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / metabolism
  • rab1 GTP-Binding Proteins / genetics
  • rab1 GTP-Binding Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • FNDC5 protein, human
  • Fibronectins
  • Membrane Proteins
  • Nuclear Proteins
  • RAB1A protein, human
  • Repressor Proteins
  • TLR3 protein, human
  • TRIB3 protein, human
  • Toll-Like Receptor 3
  • Jumonji Domain-Containing Histone Demethylases
  • KDM5B protein, human
  • Histone Acetyltransferases
  • histone acetyltransferase type B complex
  • Protein Serine-Threonine Kinases
  • Amyloid Precursor Protein Secretases
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • FURIN protein, human
  • Furin
  • ADAM10 Protein
  • ADAM10 protein, human
  • SIRT1 protein, human
  • Sirtuin 1
  • HDAC2 protein, human
  • Histone Deacetylase 2
  • rab1 GTP-Binding Proteins