Sex-specific differences of plasma lipidomic profile in young healthy individuals

Lipidomics of human tissues and fluids continuously gains importance for the identification of new biomarker as risk indicators for a wide variety of diseases. However, due to the differences in analytical methods and biased selection of study populations there are no generally accepted reference values. We aimed to define sex-specific reference values and their variance for major lipid classes of human blood plasma.

The study cohort comprised 35 women and 36 men, age 19 to 33 years, with normal laboratory data and BMI within a clinically acceptable range. 205 lipid species from 13 major lipid classes were quantified by shotgun lipidomics on a Q Exactive mass spectrometer and sex-hormone profile was characterized by estradiol (E2), testosterone, cortisol, DHEA, LH, and FSH.

Non-parametric tests established statistically significant sex-specific differences of cholesterol esters (CE), phosphatidylethanolamines (PE), phosphatidylinositols (PI), sphingomyelins (SM), phosphatidylcholines (PC), lysophosphatidylcholines (LPC), and lysophosphatidylethanolamine ethers (LPC-O). Significantly lower plasma concentrations in men were observed for 9 out of 10 PE species, 7 out of 8 PI species, 24 out of 26 SM species, and 22 out of 29 PC species, whereas 11 out of 13 LPC and 3 out of 3 LPC-O species were significantly higher in men. Analyzing quartiles of E2 revealed a stepwise decrease of PE-, PI-, and PC-species, whereas SM and PC-O remained unchanged. Also a stepwise decrease of TAG 58:6 and 58:7 could be associated with higher E2 level. We observed strong impact of sex-specific hormones in females, however free testosterone did not affect plasma lipidome in males.

Our data indicated the importance of representative gender-specific cohorts for clinical lipidomics population screens together with accurate accounting of individual hormonal status of each female subject.