Dysregulated lipidome of sebum in patients with atopic dermatitis

Abstract

Background: Lipids are the major components of skin barrier, mainly produced by keratinocytes and sebaceous glands. Previous studies on barrier dysfunction of atopic dermatitis (AD) mainly focus on the lipids from keratinocytes, whereas the role of sebaceous gland-derived lipids in AD has long been underrecognized. Methods:The sebum secreted on the skin surface of AD patients was measured using the Delfin Sebum Scale. Sebum was collected using Sebutape patches and subjected for liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis.Multivariate data analysis was applied to explore the relationship among the lipidome, clinical features, and sebaceous gland-related molecules. Results:The amount of sebum secreted from sebaceous glands was decreased in AD patients and was negatively correlated with the barrier function and disease severity. LC-MS/MS revealed the lipidome of sebum, which clustered distinctly between AD patients and healthy individuals. Among the differential lipid subclasses, triglycerides (TG) were exclusively decreased in AD patients and correlated with disease severity.The first principal component scores of AD patients, which represented the main signature of the lipidome, were positively correlated with the SCORAD scores and were significantly different across the patient groups with differential clinical symptoms such as skin dryness and pruritus. Further analysis on the previously published transcriptome data revealed aberrant expression of lipid metabolism-related genes in non-lesional skin of AD patients, which was associated with skin inflammation and barrier dysfunction and mainly derived from inner root sheath keratinocytes and sebaceous gland cells.

Biosignatures of defective sebaceous gland activity in sebum‐rich and sebum‐poor skin areas in adult atopic dermatitis

“…39 A recent paper has reported dysregulation of sebum production in AD in keeping with aberrant expression of genes regulating lipid biosynthetic pathways, including FA de novo synthesis, elongation and desaturation. 52 While the lipid domains evaluated in previous studies differed from those addressed here, coincident results were obtained on the significant depletion of TGs in AD sebum. Our approach addressed sebum-specific biomarkers, e.g., squalene, sapienate and branched FFAs, indicating compromised early events in the lipid cascade leading to sebaceous end products, including TGs and WEs.…”

“…Expression of enzymes involved in the elongation of FFAs present with different distribution in AD epidermis 39 . A recent paper has reported dysregulation of sebum production in AD in keeping with aberrant expression of genes regulating lipid biosynthetic pathways, including FA de novo synthesis, elongation and desaturation 52 . While the lipid domains evaluated in previous studies differed from those addressed here, coincident results were obtained on the significant depletion of TGs in AD sebum.…”

“…Omics technologies, which include metabolomics and lipidomics, are strategic in the interpretation of the complexity opposed by the barrier anomalies in AD. 23,[49][50][51][52] This study focused on the occurrence of AD skin manifestations in facial areas in addition to the forearm, which is a SGP area. We evaluated non-invasive samples of the skin surface lipids from SGR and SGP areas.…”

Recent advances in the epithelial barrier theory

“…Dysbiosis of the skin microbiota and opportunistic bacteria colonization is common in AD ( 163 ). Recent studies found that the opportunistic pathogen S. aureus was shown to cause barrier damage via disruption of the lipid composition, which is crucial for skin barrier integrity and causing inflammation in skin ( 116 , 161 , 164 , 165 ). Interestingly, Stuvel et al .…”

Resolving the etiology and treatments of allergic diseases

“…The role of lipids from sebaceous glands in barrier dysfunction of atopic dermatitis (AD) has been under‐recognized. Yin and colleagues 9 noticed that aberrant lipid metabolism in sebaceous glands was correlated with skin inflammation and barrier dysfunction, and contributed to the pathogenesis of AD. Another group indicated that human CST1 protein suppressed asthma symptoms by protecting the asthmatic bronchial epithelial barrier through inhibiting allergenic protease activity, indicating CST1 as a potential biomarker for asthma control 10 .…”