Abstract
BackgroundRecent technical advances in the extraction of dermal interstitial fluid (ISF) have stimulated interest in using this rather unexploited biofluid as an alternative to blood for detection and prediction of disease. However, knowledge about the presence of useful biomarkers for health monitoring in ISF is still limited. In this study, we characterized the lipidome of human suction blister fluid (SBF) as a surrogate for pure ISF and compared it to that of plasma.MethodsPlasma and SBF samples were obtained from 18 healthy human volunteers after an overnight fast. Total lipids were extracted and analyzed by liquid chromatography-tandem mass spectrometry. One hundred ninety-three lipid species covering 10 complex lipid classes were detected and quantified in both plasma and SBF using multiple reaction monitoring. A fraction of the lipid extract was subjected to alkaline transesterification and fatty acid methyl esters were analyzed by gas chromatography–mass spectrometry.ResultsThe total concentration of lipids in SBF was 17% of the plasma lipid concentration. The molar fraction of lipid species within lipid classes, as well as total fatty acids, showed a generally high correlation between plasma and SBF. However, SBF had larger fractions of lysophospholipids and diglycerides relative to plasma, and consequently less diacylphospholipids and triglycerides. Principal component analysis revealed that the interindividual variation in SBF lipid profiles was considerably larger than the within-subject variation between plasma and SBF.ConclusionsPlasma and SBF lipid profiles show high correlation and SBF could be used interchangeably with blood for the analysis of major lipids used in health monitoring.
Highlights
The interstitial space in tissue is filled with interstitial fluid (ISF), which enables cell-to-cell interactions and provides a matrix for the transport of nutrients and metabolic waste between cells and capillaries
Comparison of lipid profiles in plasma and suction blister fluid To compare the overall lipid profiles of plasma and SBF, a total lipid extract was prepared from pooled plasma or SBF samples from 18 healthy individuals and analyzed by liquid chromatography–mass spectrometry (LC-MS) in MS2 scan mode with positive (ESI+)(Fig. 1a) and negative (ESI-) ionization (Fig. 1b)
Analysis in positive mode primarily yielded [M + H]+ ions for phospholipids and [M + NH4]+ for neutral lipids, including cholesteryl esters (CEs) and di- and triglycerides (DGs and TGs, respectively)
Summary
The interstitial space in tissue is filled with interstitial fluid (ISF), which enables cell-to-cell interactions and provides a matrix for the transport of nutrients and metabolic waste between cells and capillaries. Recent technical advances allowed the development of a new generation of minimally invasive devices aimed at extracting ISF, and thereby evoked a resurgence of interest in this matrix for health status monitoring. Microneedles have been demonstrated to extract an analytical volume of dermal ISF from humans that is sufficient for determining transcriptomic [3] and proteomic signatures [3, 4] as well as other biomarkers [5]. ISF is a Nilsson et al Lipids in Health and Disease (2019) 18:164 relatively simple matrix compared to blood, allowing more facile isolation and characterization of certain molecular compounds. Recent technical advances in the extraction of dermal interstitial fluid (ISF) have stimulated interest in using this rather unexploited biofluid as an alternative to blood for detection and prediction of disease. We characterized the lipidome of human suction blister fluid (SBF) as a surrogate for pure ISF and compared it to that of plasma
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