title: Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota?
abstract: We tested whether oxidized linoleic acid metabolites (OXLAM) are associated with pediatric metabolic syndrome (MetS) and a proatherogenic lipoprotein profile in 122 obese adolescents. Furthermore, we examined whether genetic and metagenomic factors can modulate plasma OXLAM concentrations by genotyping thefatty acid desaturase 1/2(FADS) gene and by characterizing the gut microbiota. Subjects with MetS (n= 50) showed higher concentrations of 9- and 13-oxo-octadecadienoic acid (9- and 13-oxo-ODE) than subjects without MetS (n= 72). Both metabolites were associated with an adverse lipoprotein profile that was characterized by elevated very small-dense low-density lipoprotein (p< 0.005) and large very low-density lipoprotein particles (p= 0.01). Plasma 9- and 13-oxo-ODE were higher in subjects carrying the haplotype AA of theFADSgene cluster (p= 0.030 andp= 0.048, respectively). Furthermore, the reduced gut bacterial load was associated with higher 9-oxo-ODE concentrations (p= 0.035). This is the first study showing that high plasma OXLAM concentrations are associated with MetS and suggesting that the leading factors for high plasma concentrations of OXLAM might be the genetic background and the composition of the gut microbiota. In conclusion, high concentrations of 9- and 13-oxo-ODE, which may be the result of a genetic predisposition and a reduced gut bacterial load, are associated with MetS and with a proatherogenic lipoprotein profile in obese adolescents.
authors.affiliation: 1 Department of Internal Medicine, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Domenico
authors.initials: D
authors.lastname: Tricò
authors.affiliation: 2 Department of Pediatrics, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Sessa
authors.affiliation: 2 Department of Pediatrics, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Sonia
authors.initials: S
authors.lastname: Caprio
authors.affiliation: 3 Department of Medicine, Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
authors.affiliation: 4 Purdue School of Pharmacy, Purdue University , West Lafayette, Indiana.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Liu
authors.affiliation: 3 Department of Medicine, Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Tiebing
authors.initials: T
authors.lastname: Liang
authors.affiliation: 5 Department of Molecular and Cell Biology, University of Connecticut , Hartford, Connecticut.
authors.forename: Joerg
authors.initials: J
authors.lastname: Graf
authors.affiliation: 1 Department of Internal Medicine, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Raimund I
authors.initials: RI
authors.lastname: Herzog
authors.affiliation: 6 Department of Pediatrics, University of California San Diego , San Diego, California.
authors.forename: Casey D
authors.initials: CD
authors.lastname: Johnson
authors.affiliation: 2 Department of Pediatrics, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Giuseppina Rosaria
authors.initials: GR
authors.lastname: Umano
authors.affiliation: 6 Department of Pediatrics, University of California San Diego , San Diego, California.
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Feldstein
authors.affiliation: 2 Department of Pediatrics, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers; D002648:Child; D000090943:Delta-5 Fatty Acid Desaturase; D004198:Disease Susceptibility; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D005260:Female; D000069196:Gastrointestinal Microbiome; D000068617:Genetic Background; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D019787:Linoleic Acid / Q000378:metabolism*; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D055442:Metabolome; D009765:Obesity / Q000150:complications / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D015415:Biomarkers; D000090943:Delta-5 Fatty Acid Desaturase; D008074:Lipoproteins; D019787:Linoleic Acid; D044943:Fatty Acid Desaturases; C533241:FADS2 protein, human
keywords: genetic predisposition; gut microbiota; linoleic acid; metabolic syndrome; oxidized low-density lipoproteins; oxidized metabolites of linoleic acid; pediatric obesity