Dietary ceramide 2-aminoethylphosphonate, a marine sphingophosphonolipid, improves skin barrier function in hairless mice

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. 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. In this study, we focused on the function to retain water in the epidermis as the skin barrier and the epidermal structures which conducive to the barrier. Lipid lamellae in the extracellular space of corneocytes play a vital role in the barrier function and maintain a hydrophobic environment. These lipids, consisting of 50% ceramides, 25% cholesterol, and 15% fatty acids (on a total lipid mass basis), contribute to the water-holding properties and prevent desiccation by TEWL 1,3. Ceramide formation occurs by binding of a fatty acid to an amide group of the sphingoid base. The molecular structures of ceramides are various. Ceramides are essential for the skin barrier function since changes in ceramide profile of the lipid lamellae have been associated with impaired barrier function 4-10. The structure formed by the binding of ω-hydroxyceramides to cornified envelope proteins is important for the skin barrier 11,12. The cornified envelope is a rigid structure with an outer lipid layer and an inner protein, which is produced by the crosslinking of precursor proteins such as involucrin and loricrin 13. Ultra-long-chain ceramide participates in the formation of covalently bound ω-hydroxyceramides 14,15. The amount of covalently bound ω-hydroxyceramides correlates with skin hydration and skin barrier function 11,12,16. Sphingoid base is a common structure of sphingolipids which are one of the major families of lipids. Since sphingolipids are components of cell membranes, they are ubiquitous in eukaryotic organisms 17. However, the polar head groups and ceramide structure of sphingolipids vary amo...

Metabolomic analysis of gut metabolites in patients with colorectal cancer: Association with disease development and outcome

“…The metabolomic analysis of the present study revealed that several metabolites, such as 2-aminoethylphosphonate, were enriched in the CRA and CRC groups compared with the HC group. 2-Aminoethylphosphonate is a potentially nutritionally active phosphatidyl sphingolipid that significantly increases the content of hydroxy ceramides, which play an important role in the expression of genes related to its biosynthesis-related genes in the skin ( 29 ). Amino acids play an important role in several steps of protein biosynthesis, where they maintain redox homeostasis as both electron donors and acceptors and act as energy sources ( 30 ).…”

Dietary Phospholipids Prepared From Scallop Internal Organs Attenuate the Serum and Liver Cholesterol Contents by Enhancing the Expression of Cholesterol Hydroxylase in the Liver of Mice

“…No studies have reported the inhibition of cholesterol absorption by CAEP, a sphingolipid possessing a carbon-phosphorus bond, and is often found in bivalves. However, CAEP is hydrolyzed to sphingoid base during the digestive process and can interfere with cholesterol absorption ( 44 ). In this study, SOY-PL contained PtdCho and PtdEtn, and SCO-PL contained PtdCho, PtdEtn, and CAEP.…”

Sphingolipids as Functional Food Components: Benefits in Skin Improvement and Disease Prevention

“…Although most of these animal studies were conducted using models with disrupted skin caused by ultraviolet (UV) exposure, sodium dodecyl sulfate (SDS) treatment, tape-stripping, and a special commercial diet (HR-AD), a few reports on animals under normal conditions are available (Table ). HR-AD is a magnesium-deficient diet that induces skin damage and atopic dermatitis-like skin symptoms, although the causative mechanism is not clear. , After causing skin perturbation by feeding hairless mice a HR-AD, dietary supplementation of plant-derived glucosylceramide, sphingomyelin, and CAEP can accelerate the recovery of their skin damage, such as increased TEWL and decreased stratum corneum hydration, by changing to a normal diet. − In addition, the direct addition of sphingolipids, including plant-derived glucosylceramide and milk-derived sphingomyelin, to the HR-AD diet drastically suppresses skin damage. − Exposure to UV radiation is a key factor in the initiation of photoaging and can be characterized by dryness, wrinkling, and mottled pigmentation . Mice with a single-dose UVB-irradiated dorsal skin (20–200 mJ/cm 2 ) were used as the damaged skin model.…”

“…The structure formed by the binding of ω-hydroxyceramides to cornified envelope proteins plays an important role in skin barrier function . In addition, dietary CAEP (from squid) and glucosylceramide (from maize) significantly increased the content of covalently bound ω-hydroxyceramides, and the expression of their biosynthesis-related genes in the skin of HR-AD mice . Considering this evidence, the difference in sphingolipid structures, especially sphingoid bases, is not crucial for the activation of de novo ceramide synthesis in the epidermis.…”