title: Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.
abstract: BACKGROUND
  Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models.
  
  
  METHODS
  Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity.
  
  
  RESULTS
  The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers.
  
  
  CONCLUSIONS
  This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Rodriguez-Perez
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Schiavi
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.|Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Frei
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.|Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Ferstl
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.|Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Wawrzyniak
authors.affiliation: Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland.|"ALL-MED" Medical Research Institute, Wroclaw, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Smolinska
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.|Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Sokolowska
authors.affiliation: Pulmonary Division, University Hospital of Zürich, Zürich, Switzerland.
authors.forename: N A
authors.initials: NA
authors.lastname: Sievi
authors.affiliation: Pulmonary Division, University Hospital of Zürich, Zürich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Kohler
authors.affiliation: Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.|Allergy Unit, Department of Dermatology, University Hospital of Zürich, Zürich, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Schmid-Grendelmeier
authors.affiliation: Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK.
authors.forename: D
authors.initials: D
authors.lastname: Michalovich
authors.affiliation: Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK.
authors.forename: K D
authors.initials: KD
authors.lastname: Simpson
authors.affiliation: Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK.
authors.forename: E M
authors.initials: EM
authors.lastname: Hessel
authors.affiliation: Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland.|"ALL-MED" Medical Research Institute, Wroclaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Jutel
authors.affiliation: Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martin-Fontecha
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Palomares
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.|Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
authors.forename: C A
authors.initials: CA
authors.lastname: Akdis
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
authors.forename: L
authors.identifier: http://orcid.org/0000-0003-4705-3583
authors.initials: L
authors.lastname: O'Mahony
mesh_terms: D000818:Animals; D001249:Asthma / Q000201:enzymology / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000201:enzymology; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D051379:Mice; D009765:Obesity; D012130:Respiratory Hypersensitivity / Q000201:enzymology; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D013230:Stearoyl-CoA Desaturase
keywords: asthma; epithelial cells; fatty acids; obesity; stearoyl-coenzyme A desaturase