Lipids are important structural and functional components of the skin. Alterations in the lipid composition of the epidermis can lead to diminished barrier function of the skin and are associated with diseases like atopic dermatitis. SHARPIN-deficient cpdm mice develop a chronic dermatitis with similarities to atopic dermatitis in humans. Here, we used a new mass spectrometry analytical strategy named multiple reaction monitoring (MRM) profiling to rapidly identify discriminative lipid ions. Shorter fatty acyl residues and increased relative amounts of sphingosine ceramides were observed in cpdm epidermis compared to wild type mice. These changes were accompanied by downregulation of the Fasn gene which encodes fatty acid synthase. Fast screening of more than 300 ion pairs (representing a parent molecule and a fragment) related to diverse lipids allowed phenotypical profiling and discrimination of cpdm and wild type mice. Tentative attribution of the most significant ion pairs was confirmed by product ion screening (MS/MS). Relative quantification of sphingosine ceramides CerAS(d18:1/24:0)OH, CerAS(d18:1/16:0)OH and CerNS(d18:1/16:0) could discriminate between the two groups with 100% accuracy, while the free fatty acids cerotic acid, 16-hydroxy palmitic acid, and docosahexaenoic acid (DHA) had a 96.4% of accuracy. MRM profiling is proposed as an accelerated prospective biomarker discovery approach.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Atopic dermatitis, Metabolomics
Principal Investigators: (in alphabetical order) |
Harm HogenEsch |
Submitting User: | francojackeline |
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