Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota?

Antioxid Redox Signal. 2019 Jan 10;30(2):241-250. doi: 10.1089/ars.2017.7049. Epub 2017 Apr 7.

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 the fatty 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 the FADS gene cluster (p = 0.030 and p = 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.

Keywords: genetic predisposition; gut microbiota; linoleic acid; metabolic syndrome; oxidized low-density lipoproteins; oxidized metabolites of linoleic acid; pediatric obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Biomarkers
  • Child
  • Disease Susceptibility*
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism
  • Female
  • Gastrointestinal Microbiome
  • Genetic Background
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Linoleic Acid / metabolism*
  • Lipid Metabolism
  • Lipoproteins / metabolism
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / etiology*
  • Metabolic Syndrome / metabolism*
  • Metabolome
  • Obesity / complications
  • Obesity / metabolism
  • Oxidation-Reduction*

Substances

  • Biomarkers
  • Lipoproteins
  • Linoleic Acid
  • Fatty Acid Desaturases
  • FADS2 protein, human
  • delta-5 fatty acid desaturase