Plasma lipid profiling in a large population-based cohort

Abstract

This article is available online at http://www.jlr.org Circulating lipids, their biosynthesis, metabolism, and biological functions are intimately involved in many complex disease processes ( 1 ). Traditional clinical chemistry uses measurements of total cholesterol, triglycerides, and HDL as tools for determining health status and disease risk. The tests for these lipids are low cost, high throughput, and well established. The development of soft ionization techniques, particularly electrospray ionization has proven to be a watershed for lipidomics, allowing the detection and quantifi cation of individual molecular species. Recently, the Lipid Maps Consortium described a detailed analysis of the plasma lipidome, reporting on the concentration of nearly 600 lipids in pooled human plasma from healthy individuals ( 1, 2 ). This analysis highlighted the complexity of the plasma lipidome and the potential of plasma lipid profi ling for disease classifi cation, risk assessment, and to uncover changes in lipid metabolism associated with disease states. To date, plasma lipid profi ling has been used to identify lipidomic biomarkers associated with a variety of diseases and activities related to obesity ( 3 ), hypertension ( 4 ), smoking ( 5 ), cystic fi brosis ( 6 ), weight loss ( 7 ), and type 2 diabetes ( 8 ). These studies have, in general, have been conducted using relatively small cohorts (<100 participants) ( 3, 4, 6, 7 ) and/or limited coverage of the lipidome (<100 species) ( 4, 6, 8 ).Abstract We have performed plasma lipid profi ling using liquid chromatography electrospray ionization tandem mass spectrometry on a population cohort of more than 1,000 individuals. From 10 l 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 identifi ed statistically signifi cant 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 signifi cantly 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. -Weir, J. M., G.

Demographic and clinical variables affecting mid‐ to late‐life trajectories of plasma ceramide and dihydroceramide species

“…A number of cross‐sectional studies have reported sex differences in circulating ceramides (Hammad et al ., 2010; Bui et al ., 2012; Ishikawa et al ., 2013; Weir et al ., 2013). Typically, women have higher blood levels of most ceramides compared with men.…”

“…Previous, carefully validated, studies have utilized small sample sizes of 10–15 individuals aged 20–40 years (Hammad et al ., 2010; Bui et al ., 2012) or have used pooled samples (Quehenberger et al ., 2010). A recent population‐based study performed plasma lipid profiling in over 1000 individuals, median age of 36, enrolled in the San Antonio Family Heart Study (Weir et al ., 2013). This study showed important cross‐sectional associations between ceramides and dihydroceramides (DHCer) and psychological and demographic factors.…”

Circulating ceramides are inversely associated with cardiorespiratory fitness in participants aged 54–96 years from the Baltimore Longitudinal Study of Aging

“…Independent of potential confounders, sex differences were confirmed for C16:0, C18:0, C20:0, C24:1 ceramides and C20:0 dihydroceramide, with men showing a significantly stronger association between higher levels of ceramides and poor aerobic capacity as compared to women. This interesting finding is in keeping with previous cross‐sectional studies that reported gender differences in plasma levels of ceramides, with women generally showing higher concentrations of ceramides then men (Hammad et al ., 2010; Bui et al ., 2012; Ishikawa et al ., 2013; Weir et al ., 2013). Longitudinal sex differences in the levels of ceramides with aging were also previously described in BLSA population, with women showing a steeper trajectory of increase than men (Mielke et al ., 2015).…”

The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice

“…Extracts were centrifuged (3,350 g, 5 min), and the supernatant stored in glass vials with Teflon insert caps at À 80°C until required. Lipid analysis was performed on lipid extracts (5 ml; sonicated in a water bath for 30 min at RT before use) by liquid chromatography electrospray ionization tandem mass spectrometry using an Agilent 1,200 liquid chromatography system and an Applied Biosystems API 4,000 Q/TRAP mass spectrometer with a turbo-ionspray source (350°C) 66,67 . Data were analysed in Multiquant 2.1 software and specific lipid species normalized to total phosphatidylcholine levels.…”