Plasma High-Resolution Metabolomics Differentiates Adults with Normal Weight Obesity from Lean Individuals

Obesity (Silver Spring). 2019 Nov;27(11):1729-1737. doi: 10.1002/oby.22654.

Abstract

Objective: This study explored underlying metabolism-related dysfunction by examining metabolomic profiles in adults categorized as lean, as having normal weight obesity (NWO), or as having overweight/obesity.

Methods: Participants (N = 179) had fasting plasma analyzed by liquid chromatography and high-resolution mass spectrometry for high-resolution metabolomics. Body composition was assessed by dual-energy x-ray absorptiometry. NWO was defined as BMI < 25 and body fat > 30% for women and > 23% for men. Differentiating metabolomic features were determined by using linear regression models and likelihood ratio tests with false discovery rate correction. Mummichog was used for pathway and network analyses.

Results: A total of 222 metabolites significantly differed between the groups at a false discovery rate of q = 0.2. Linoleic acid, β-alanine, histidine, and aspartate/asparagine metabolism pathways were significantly enriched (all P < 0.01) by metabolites that were similarly upregulated in the NWO and overweight/obesity groups compared with the lean group. A module analysis linked branched-chain amino acids and amino acid metabolites as elevated in the NWO and overweight/obesity groups compared with the lean group (all P < 0.05).

Conclusions: Metabolomic profiles of individuals with NWO reflected similar metabolic disruption as those of individuals with overweight/obesity. High-resolution metabolomics may help identify people at risk for developing obesity-related disease, despite normal BMI.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Body Composition
  • Body Mass Index
  • Female
  • Humans
  • Male
  • Metabolomics / methods*
  • Middle Aged
  • Obesity / metabolism*
  • Obesity / pathology