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

ObjectiveThis 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. MethodsParticipants (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. ResultsA total of 222 metabolites significantly differed between the groups at a false discovery rate of q=0.2. Linoleic acid, beta -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). ConclusionsMetabolomic 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.