Impact of solar irradiation on lipidome dynamics and disruption using an in vitro 3D reconstructed epidermis model and a combination of advanced analytical methods.

Objective: Solar irradiation can lead to harmful effects such as skin ageing and cancer. Therefore, the aim of this work was to provide a better understanding of the skin composition and the molecular mechanisms underlying solar-induced damage.

Methods: We measured the impact of sun exposure on the lipidome of a 3D reconstructed human epithelial (RHE) in vitro model, as well as the protective role of a commercial SPF50+ sunscreen on the lipid modulations. MALDI-MSI was used to locate several lipids identified using LC-MS/MS to determine changes in their distribution in the epidermis.

Results: There were 252 lipids in RHE models deregulated by irradiation, including multiple phospholipid classes, triacylglycerols, diacylglycerols, sphingolipids, and ceramides. Of these, only four were still modulated when the sunscreen was applied prior to irradiation. MALDI-MSI imaging of control RHE sections alongside optical images detected 4115 lipids which were tentatively identified using the LipidMaps database associated with distinct areas in the tissue. One key lipid linked to keratinocyte differentiation during photoaging, 25-hydroxycholesterol, was present in low levels in control RHE models but increased significantly after irradiation. The increase was prevented by applying sunscreen prior to irradiation.

Conclusion: A combination of LC-MS/MS and MALDI-MSI enabled the analysis of lipids involved in key pathways altered by irradiation, as well as their location in the epidermis. Importantly, the SPF50+ sunscreen exhibited a protective effect on the epidermis lipidome against modulations due to irradiation. This technology will enable biomarker and pathway-specific events in the epidermis to be monitored after different treatments.