Plasma metabolome analysis identifies distinct human metabotypes in the postprandial state with different susceptibility to weight loss-mediated metabolic improvements

Healthhasbeendefinedas the capability of the organismto adapt to challenges. Inthis study,we testedto what extent comprehensively phenotyped individuals reveal differences in metabolic responses to a standardized mixedmeal tolerance test (MMTT) and howthese responses changewhen individuals experiencemoderateweight loss.Metabolome analysiswas used in 70 healthy individuals.with profiling of~300 plasmametabolites during an MMTT over 8 h.Multivariate analysis of plasma markers of fatty acid catabolismidentified 2 distinct metabotype clusters (AandB). Individuals frommetabotypeBshowed slower glucose clearance, had increased intra-abdominal adipose tissuemass and higherhepatic lipid levelswhen comparedwith individuals frommetabotypeA.AnNMRbased urine analysis revealed that these individuals also to have a less healthy dietary pattern.After aweight loss of ~5.6 kg over 12wk, only the subjects frommetabotype B showed positive changes in the glycemic response during the MMTT and in markers of metabolic diseases. Our study in healthy individuals demonstrates that more comprehensive phenotyping can reveal discretemetabotypeswith different outcomes in a dietary intervention and that markers of lipid catabolism in plasma could allow early detection of the metabolic syndrome. 7copy; FASEB.