Healthy plasma lipidomic signatures depend on sex, age, body mass index, and contraceptives but not perceived stress

Perceived stress is thought to contribute to the pathogenesis of metabolic, vascular, mental, and immune diseases, with different susceptibilities in women and men. The present study investigated if and how perceived stress and/or demographic variables including sex, age, body mass index, regular prescription drugs, occasional analgesics, or dietary supplements manifested in plasma lipidomic profiles, obtained by targeted and untargeted mass spectrometry analyses. The study included 217 healthy women and 108 healthy men, aged 18-68 years, who were recruited in a 2:1 female:male ratio to account for women with/without contraceptives. As expected, dehydroepiandrosterone sulfate (DHEAS) and ceramides were higher in men than women, and DHEAS decreased with age, while ceramides increased. Contrary to expectations, neither DHEAS nor ceramides were associated with perceived stress (PSQ30 questionnaire), which was however, associated with BMI in men, but not in women. None of the lipid species or classes showed a similar "age X sex X BMI" interaction, but the endocannabinoid palmitoylethanolamide (PEA) correlated with BMI and hypertension. Independent of perceived stress, lysophosphatidylcholines (LPCs) were lower in women than men, whereas LPC metabolites, lysophosphatidic acids (LPAs), were higher in women. The LPA:LPC ratio was particularly high in women using oral contraceptives suggesting a strong hormone-induced extracellular conversion of LPCs to LPAs, which is catalyzed by the phospholipase D, autotaxin. The results reveal complex sex differences in perceived stress and lipidomic profiles, the latter being exacerbated by contraceptive use, but perceived stress and lipids were not directly correlated.