Plasma lipid profiling in a large population-based cohort

Melissa A. Greeve,Joanne E. Curran,Jonathan Shaw,Anthony G. Comuzzie,Jacquelyn M. Weir,John Blangero,Adam Kowalczyk,Michael C. Mahaney,Gerard Wong,Laura Almasy,Christopher K. Barlow,Peter J. Meikle,Jeremy B.M. Jowett

doi:10.1194/jlr.p035808

Abstract

We have performed plasma lipid profiling using liquid chromatography electrospray ionization tandem mass spectrometry on a population cohort of more than 1,000 individuals. From 10 μl of plasma we were able to acquire comparative measures of 312 lipids across 23 lipid classes and subclasses including sphingolipids, phospholipids, glycerolipids, and cholesterol esters (CEs) in 20 min. Using linear and logistic regression, we identified statistically significant associations of lipid classes, subclasses, and individual lipid species with anthropometric and physiological measures. In addition to the expected associations of CEs and triacylglycerol with age, sex, and body mass index (BMI), ceramide was significantly higher in males and was independently associated with age and BMI. Associations were also observed for sphingomyelin with age but this lipid subclass was lower in males. Lysophospholipids were associated with age and higher in males, but showed a strong negative association with BMI. Many of these lipids have previously been associated with chronic diseases including cardiovascular disease and may mediate the interactions of age, sex, and obesity with disease risk.

Highlights

We have performed plasma lipid profiling using liquid chromatography electrospray ionization tandem mass spectrometry on a population cohort of more than 1,000 individuals
This analysis highlighted the complexity of the plasma lipidome and the potential of plasma lipid profiling for disease classification, risk assessment, and to uncover changes in lipid metabolism associated with disease states
The reverse phase chromatography resulted in the coelution of different lipid classes (Fig. 1), it did provide clear separation of isobaric species within each class such that isobaric species of PC(O), PC(P), and PC were well separated (Fig. 2A, supplementary Table I)

Summary

Introduction

We have performed plasma lipid profiling using liquid chromatography electrospray ionization tandem mass spectrometry on a population cohort of more than 1,000 individuals. Plasma lipid profiling has been used to identify lipidomic biomarkers associated with a variety of diseases and activities related to obesity [3], hypertension [4], smoking [5], cystic fibrosis [6], weight loss [7], and type 2 diabetes [8] These studies have, in general, have been conducted using relatively small cohorts (

Methods

Results

Conclusion