An individual participant data meta-analysis on metabolomics profiles for obesity and insulin resistance in European children

Sci Rep. 2019 Mar 25;9(1):5053. doi: 10.1038/s41598-019-41449-x.

Abstract

Childhood obesity prevalence is rising in countries worldwide. A variety of etiologic factors contribute to childhood obesity but little is known about underlying biochemical mechanisms. We performed an individual participant meta-analysis including 1,020 pre-pubertal children from three European studies and investigated the associations of 285 metabolites measured by LC/MS-MS with BMI z-score, height, weight, HOMA, and lipoprotein concentrations. Seventeen metabolites were significantly associated with BMI z-score. Sphingomyelin (SM) 32:2 showed the strongest association with BMI z-score (P = 4.68 × 10-23) and was also closely related to weight, and less strongly to height and LDL, but not to HOMA. Mass spectrometric analyses identified SM 32:2 as myristic acid containing SM d18:2/14:0. Thirty-five metabolites were significantly associated to HOMA index. Alanine showed the strongest positive association with HOMA (P = 9.77 × 10-16), while acylcarnitines and non-esterified fatty acids were negatively associated with HOMA. SM d18:2/14:0 is a powerful marker for molecular changes in childhood obesity. Tracing back the origin of SM 32:2 to dietary source in combination with genetic predisposition will path the way for early intervention programs. Metabolic profiling might facilitate risk prediction and personalized interventions in overweight children.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers*
  • Body Mass Index
  • Body Weights and Measures
  • Child
  • Child, Preschool
  • Chromatography, Liquid
  • Female
  • Follow-Up Studies
  • Humans
  • Insulin Resistance*
  • Male
  • Metabolome*
  • Metabolomics* / methods
  • Pediatric Obesity / etiology
  • Pediatric Obesity / metabolism*
  • Tandem Mass Spectrometry

Substances

  • Biomarkers