BACKGROUND & AIMS: Metabolically unhealthy overweight (MUO) individuals and metabolically healthy overweight (MHO) individuals differ in biomarkers of atherogenesis. Metabolomic approaches enable studies of the metabolic variables underlying these differences.

METHODS

We determined the metabolomes in plasma samples from 34 MUO and 34 MHO individuals matched for sex, age, and body mass index (BMI) to identify potential metabolic markers or pathways associated with atherogenic traits.

RESULTS

This analysis revealed that the MUO group had significantly higher levels of glycolic acid, 6 lysophosphatidylethanolamines (lysoPEs), and 12 lysophosphatidylcholines (lysoPCs). Although the two groups had similar total body fat percentages and lean body masses, MUO individuals had larger visceral fat areas (VFAs). They also had greater circulating lipoprotein-associated phospholipase A (Lp-PLA) activity and higher levels of oxidized low-density lipoprotein (ox-LDL) and urinary 8-epi-prostaglandin F (8-epi-PGF), reflecting higher risks for oxidative and lipid-related tissue damage. The following measures were positively correlated: VFA and ox-LDL; ox-LDL and Lp-PLA activity; and lysoPC, lysoPE, and 8-epi-PGF levels. Chronic plasma lysoPC increases were associated with atherogenic traits, higher levels of mean ox-LDL, 8-epi-PGF, Lp-PLA, and visceral fat accumulation in MUO compared to MHO individuals.

CONCLUSIONS

This panel of plasma metabolites distinguishes MUO from MHO individuals and will enable future research on fat dysregulation and obesity.