Effects of atopic dermatitis and gender on sebum lipid mediator and fatty acid profiles

Authors: AGRAWAL, KARAN - University Of California, Davis; HASSOUN, LAUREN - University Of California, Davis; FOOLAD, NEGAR - University Of California, Davis; PEDERSEN, THERESA - Advanced Analytical Tech, Inc; SIVAMANI, RAJA - University Of California, Davis; Newman, John

Submitted to: Prostaglandins Leukotrienes and Essential Fatty Acids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/10/2018
Publication Date: 5/17/2018
Citation: Agrawal, K., Hassoun, L.A., Foolad, N., Pedersen, T.L., Sivamani, R.K., Newman, J.W. 2018. Effects of atopic dermatitis and gender on sebum lipid mediator and fatty acid profiles. Prostaglandins Leukotrienes and Essential Fatty Acids. 134:7-16. https://doi:10.1016/j.plefa.2018.05.001.
DOI: https://doi.org/10.1016/j.plefa.2018.05.001

Interpretive Summary: The study of skin relies heavily on the analysis of tissue biopsies or skin scrapings, however the secretions of the skin including sebum (the skins oily secretion) and sweat (the skins watery secretion) can also provide samples with biologically relevant information with a lower burden to subjects. Lipids are a broad class of important biologically relevant chemicals derived both from the diet and processes within the body, that have roles as fuels, structural components, and regulators of biological processes including skin barrier integrity, inflammation and cell growth. Some skin diseases alter lipid mediator metabolism in this tissue, however how these effects are expressed in skin secretions are poorly studied. While lipid mediators in sweat can be altered by disease, the influences of skin diseases on sebum lipid mediators are understudied. In this study we characterized sebum from subjects with and without atopic dermatitis (AD) from whom we previously characterized sweat. Specifically we measured lipid mediators including oxylipins, endocannabinoids, ceramides, sphingoid bases, and fatty acids in sebum from unaffected areas of skin from the cheeks of subjects with and without AD. Using mass spectrometry we detected 58 lipid mediators, 20 non-esterified fatty acids and 29 fatty acids from complex lipids in the sebum. Despite collection from unaffected skin, AD was associated with decreased levels of a specific subclass of lipids (i.e. C36 [NS] and [NdS] ceramide) with roles in skin barrier function. Moreover, compared to men, women showed higher concentrations of a wide variety of fatty acids and oxylipins and lower concentrations of a longer subclass of ceramides (ie. C42 [NS] and [NdS] ceramides). Additionally, sebum and sweat profiles were distinct, with sebum showing higher concentrations of most targets, but fewer highly polar lipids. Therefore, AD appears to alter sebocyte lipid metabolism even in non-lesional skin of subjects. The role of these bioactive lipids in sebum are as yet unknown, however this matrix appears valuable for the investigation of cutaneous biology in health and disease.

Technical Abstract: Lipid mediator metabolism in skin is altered in some diseases. If mediators in skin secretions are influenced by skin health, they may provide useful clinical matrices with low subject burden. While lipid mediators in sweat can be altered by disease, the influences of skin diseases on sebum lipid mediators are understudied. Here, sebum oxylipins, endocannabinoids, ceramides, sphingoid bases, and fatty acids were quantified from non-lesional bilateral cheeks of subjects with and without atopic dermatitis (AD). Using LC-MS/MS and GC-MS we quantified 58 lipid mediators, 20 non-esterified fatty acids and 29 fatty acids. AD decreased C36 [NS] and [NdS] ceramide concentrations. Females demonstrated increased concentrations of lipoxygenase-derived alcohol and ketone metabolites of linoleate, arachidonate, eicosapentanoate and docosahexanoate, increased saturated and monounsaturated non-esterified fatty acids, and decreased concentrations of C42 [NS] and [NdS] ceramides compared to males. Additionally, sebum and sweat profiles were distinct, with sebum showing higher concentrations of most targets, but fewer highly polar lipids. Therefore, AD appears to alter sebocyte lipid metabolism even in non-lesional skin of quiescent subjects. The role of these bioactive lipids in sebum are as yet unknown, however this matrix appears valuable for the investigation of cutaneous biology in health and disease.