Lipidomics for translational skin research: A primer for the uninitiated

Healthy skin depends on a unique lipid profile to form a barrier that confers protection and prevents excessive water loss, aids cell‐cell communication, and regulates cutaneous homeostasis and inflammation. Alterations in the cutaneous lipid profile can have severe consequences for skin health and have been implicated in numerous inflammatory skin conditions. Thus, skin lipidomics is increasingly of interest, and recent developments in mass spectrometry‐based analytical technologies can deliver in‐depth investigation of cutaneous lipids, providing insight into their role and mechanism of action. The choice of tissue sampling technique and analytical approach depends on the location and chemistry of the lipid of interest. Lipidomics can be conducted by various mass spectrometry approaches, including different chromatography and ionisation techniques. Targeted mass spectrometry is a sensitive approach for measuring low‐abundance signaling lipids, such as eicosanoids, endocannabinoids, and ceramides. This approach requires specific extraction, chromatography and mass spectrometry protocols to quantitate the lipid targets. Untargeted mass spectrometry reveals global changes and allows analysis of hundreds of complex lipids across a range of lipid classes, including phospholipids, glycerophospholipids, cholesteryl esters and sphingolipids. Mass spectrometry lipid imaging, including matrix‐assisted laser desorption ionisation mass spectrometry and desorption electrospray ionisation mass spectrometry, can reveal information about abundance and anatomical distribution of lipids within a single skin sample. Skin lipidomics can provide qualitative and quantitative data on hundreds of biologically‐relevant lipid species with different properties and activities, all found within a single skin sample, and support translational studies exploring the involvement of lipids in skin health and disease.