title: Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice.
abstract: Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of insulin resistance has been established. Since neutrophil elastase and myeloperoxidase are critically involved in the release of neutrophil extracellular traps (NETs), we here hypothesized that NETs may be relevant to early adipose tissue inflammation. Thus, we tested the effect of the Peptidyl Arginine Deiminase 4 inhibitor Cl-amidine, a compound preventing histone citrullination and subsequent NET release, in a mouse model of adipose tissue inflammation. C57BL6 mice received a 60% high fat diet for 10 weeks and were treated with either Cl-amidine or vehicle. Flow cytometry of adipose tissue and liver, immunohistological analysis and glucose and insulin tolerance tests were performed to determine the effect of the treatment and diet. Although high fat diet feeding induced insulin resistance no significant effect was observed between the treatment groups. In addition no effect was found in leukocyte infiltration and activation in the adipose tissue and liver. Therefore we concluded that inhibition of neutrophil extracellular trap formation may have no clinical relevance for early obesity-mediated pathogenesis of the adipose tissue and liver.
authors.affiliation: Department of Pathology, Academic Medical Center (AMC), Amsterdam, the Netherlands.|Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany.
authors.forename: Quinte
authors.initials: Q
authors.lastname: Braster
authors.affiliation: Department of Pathology, Academic Medical Center (AMC), Amsterdam, the Netherlands.|Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany.
authors.forename: Carlos
authors.initials: C
authors.lastname: Silvestre Roig
authors.affiliation: Department of Pathology, Academic Medical Center (AMC), Amsterdam, the Netherlands.
authors.forename: Helene
authors.initials: H
authors.lastname: Hartwig
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center (AMC), Amsterdam, the Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Beckers
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center (AMC), Amsterdam, the Netherlands.
authors.forename: Myrthe
authors.initials: M
authors.lastname: den Toom
authors.affiliation: Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Döring
authors.affiliation: Department of Pathology, Academic Medical Center (AMC), Amsterdam, the Netherlands.
authors.forename: Mat J
authors.initials: MJ
authors.lastname: Daemen
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center (AMC), Amsterdam, the Netherlands.|Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Lutgens
authors.affiliation: Department of Pathology, Academic Medical Center (AMC), Amsterdam, the Netherlands.|Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D065206:Extracellular Traps / Q000187:drug effects*; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C558727:N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide; D009952:Ornithine