Abstract

Sphingolipids are one of the major components of cell membranes and are ubiquitous in eukaryotic organisms. Ceramide 2-aminoethylphosphonate (CAEP) of marine origin is a unique and abundant sphingophosphonolipid with a C-P bond. Although molluscs such as squids and bivalves, containing CAEP, are consumed globally, the dietary efficacy of CAEP is not understood. We investigated the efficacy of marine sphingophosphonolipids by studying the effect of dietary CAEP on the improvement of the skin barrier function in hairless mice fed a diet that induces severely dry-skin condition. The disrupted skin barrier functions such as an increase in the transepidermal water loss (TEWL), a decrease in the skin hydration index, and epidermal hyperplasia were restored by CEAP dietary supplementation. Correspondingly, dietary CAEP significantly increased the content of covalently bound ω-hydroxyceramide, and the expression of its biosynthesis-related genes in the skin. These effects of dietary CAEP mimic those of dietary plant glucosylceramide. The novel observations from this study show an enhancement in the skin barrier function by dietary CAEP and the effects could be contributed by the upregulation of covalently bound ω-hydroxyceramide synthesis in the skin.

Highlights

  • The mammalian skin barrier is in the stratum corneum, the outermost layers of the epidermis, which protects against excessive transepidermal water loss (TEWL) and to block of irritants

  • We evaluated the effect of dietary ceramide 2-aminoethylphosphonate (CAEP) in comparison with GluCer on the skin barrier function to elucidate its mechanism of action by focusing on the synthesis of covalently bound ω-hydroxyceramides

  • Dietary GluCer significantly upregulated mRNA expression of ELOVL1 and CERS3 in the skin, compared with the HR-atopic dermatitis (AD) diet (Fig. 6A and D). These results suggested that dietary CAEP and GluCer promoted the synthesis of covalently bound ω-hydroxyceramides

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Summary

Introduction

The mammalian skin barrier is in the stratum corneum, the outermost layers of the epidermis, which protects against excessive transepidermal water loss (TEWL) and to block of irritants. Dietary sphingomyelin and GluCer enhanced mRNA expression of epidermal ceramide synthases (CERS), contributing to ultra-long-chain ceramide synthesis in the dry-skin hairless mouse ­model[26]. Sphingoid bases from dietary sphingolipids might participate in the upregulation of epidermal ultra-long-chain ceramide synthesis because sphingoid bases increase the expression of these CERS genes in normal human foreskin k­ eratinocytes[26]. Dietary milk phospholipids (consisted mainly of phosphatidylcholine and sphingomyelin) increased epidermal covalently bound ω-hydroxyceramides, and improved skin barrier function in hairless m­ ice[16]. We evaluated the effect of dietary CAEP in comparison with GluCer on the skin barrier function to elucidate its mechanism of action by focusing on the synthesis of covalently bound ω-hydroxyceramides

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