Metabolomic analysis of plasma from normal-weight adults with hypo-HDL cholesterolemia by UPLC-QTOF MS.

High-density lipoprotein cholesterol (HDL-C) is negatively correlated with atherosclerotic cardiovascular disease. The prevalence of hypo-HDL cholesterolemia is as high as 33.9%. The plasma metabolomic differences between hypo-HDL cholesterolemia populations and normal controls were investigated using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Participants with hypo-HDL cholesterolemia and normal controls were clearly discriminated from each other on the orthogonal partial least squares-discriminant analysis score plot and a total of 90 differential metabolites were identified, including down-regulated phosphatidylserine [18:0/20:3(8Z,11Z,14Z)], phosphatidylcholine [19:0/18:3(6Z,9Z,12Z)], phosphatidylserine, phosphatidylethanolamine [18:0/20:4(5Z,8Z,11Z,13E) (15Ke)], etc., and up-regulated triglyceride [15:0/18:1(9Z)/18:3(9Z,12Z,15Z)][iso6], 13-methyl-1-tritriacontene, tridodecylamine, etc. Most of the changed metabolites were lipids, notably, a significant part of which were odd chain fatty acid incorporated lipids. Carnitine shuttle was the most significant metabolic pathway, except for the disturbed glycerophospholipid metabolism, glycosphingolipid metabolism and sphingolipid metabolism in participants with hypo-HDL cholesterolemia. We identified the key metabolites and metabolic pathways that may be changed in hypo-HDL cholesterolemia participants, providing useful clues for studying the metabolic mechanisms and for early prevention of hypo-HDL cholesterolemia and dyslipidemia.