Lipid functions in skin: Differential effects of n-3 polyunsaturated fatty acids on cutaneous ceramides, in a human skin organ culture model

Abstract

Ceramides are important for skin health, with a multitude of species found in both dermis and epidermis. The epidermis contains linoleic acid-Ester-linked Omega-hydroxylated ceramides of 6-Hydroxy-sphingosine, Sphingosine and Phytosphingosine bases (CER[EOH], CER[EOS] and CER[EOP], respectively), that are crucial for the formation of the epidermal barrier, conferring protection from environmental factors and preventing trans-epidermal water loss. Furthermore, a large number of ceramides, derivatives of the same sphingoid bases and various fatty acids, are produced by dermal and epidermal cells and perform signalling roles in cell functions ranging from differentiation to apoptosis.Supplementation with the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise as therapeutic agents in a number of inflammatory skin conditions, altering the lipid profile of the skin and production of bioactive lipids such as the eicosanoids, docosanoids and endocannabinoids. In this study we wished to investigate whether EPA and DHA could also affect the ceramide profile in epidermis and dermis, and, in this way, contribute to formation of a robust lipid barrier and ceramide-mediated regulation of skin functions.Ex vivo skin explants were cultured for 6 days, and supplemented with EPA or DHA (50 μM). Liquid chromatography coupled to tandem mass spectrometry with electrospray ionisation was used to assess the prevalence of 321 individual ceramide species, and a number of sphingoid bases, phosphorylated sphingoid bases, and phosphorylated ceramides, within the dermis and epidermis.EPA augmented dermal production of members of the ceramide families containing Non-hydroxy fatty acids and Sphingosine or Dihydrosphingosine bases (CER[NS] and CER[NDS], respectively), while epidermal CER[EOH], CER[EOS] and CER[EOP] ceramides were not affected. DHA did not significantly affect ceramide production. Ceramide-1-phosphate levels in the epidermis, but not the dermis, increased in response to EPA, but not DHA.This ex vivo study shows that dietary supplementation with EPA has the potential to alter the ceramide profile of the skin, and this may contribute to its anti-inflammatory profile. This has implications for formation of the epidermal lipid barrier, and signalling pathways within the skin mediated by ceramides and other sphingolipid species. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

Seasonal changes in epidermal ceramides are linked to impaired barrier function in acne patients

“…Healthy skin produced higher levels of CER[NH] and CER[AH] in winter, suggesting adaptation to temperature, humidity or UV changes, while acne‐affected skin appears less able to do so. Currently, the mechanisms underlying seasonal changes in skin ceramides are not understood, but are likely to involve both the ceramide salvage and de novo biosynthesis pathways …”

“…A single tape‐strip per donor was used (uppermost layer of SC) to extract ceramides. A total of 283 ceramides from 10 classes were identified and analysed by ultraperformance liquid chromatography coupled to electrospray ionisation‐tandem mass spectrometry (UPLC/ESI‐MS/MS) (Appendix ) . Relative semi‐quantitation was performed using CER[N(25)S(18)] as internal standard, a ceramide found in negligible levels endogenously.…”

Lipidomics for translational skin research: A primer for the uninitiated

“…Ceramides have been implicated in diseases of epidermal barrier dysfunction, including psoriasis, atopic dermatitis and ichthyosis, and so are of clinical interest. The analysis of ceramides has progressed from simple, thin‐layer chromatography, which provides total ceramide content or analysis of the ceramide classes found in skin lipid extracts, including the complex acylceramides, through qualitative identification of individual species, to accurate identification and quantitation or semiquantitation of more than 320 ceramide species using multiple reaction monitoring by MS/MS …”

Noninvasive quantitative analysis of ceramide in skin of healthy Chinese population

“…These ceramides and cholesterol and free fatty acids, together constitute the stratum corneum lipid matrix, is an important part of the skin barrier to protect the skin from the external environment damage, reduce the loss of epidermal water. A large number of ceramides and sphingosine derivatives, a variety of fatty acids produced by the skin and epidermal cells, and in the cell function within the signal play a role in regulating cell differentiation and apoptosis . The content of ceramides directly affects the function of the skin barrier, and is closely related to the occurrence and development of many skin diseases.…”

“…A large number of ceramides and sphingosine derivatives, a variety of fatty acids produced by the skin and epidermal cells, and in the cell function within the signal play a role in regulating cell differentiation and apoptosis. 4 The content of ceramides directly affects the function of the skin barrier, and is closely related to the occurrence and development of many skin diseases. In patients with atopic dermatitis (AD), the skin shows that the cuticle lipid is damaged, the amount of physiological lipid is reduced, particularly the lack of ceramide.…”