Application of mevalonolactone prevents deterioration of epidermal barrier function by accelerating the lamellar granule lipid transport system

BACKGROUND: Fatty acids increase ATP‐binding cassette ABC transporter A12 (ABCA12) levels via an increase in peroxisome proliferator‐activated receptor β/δ (PPAR β/δ). Promoting lipid transport to lamellar granules has been suggested to improve epidermal barrier function in patients with dry skin. OBJECTIVE: We investigated whether mevalonolactone (MVL) produced by Saccharomycopsis fibuligera improves dry skin by promoting ABCA12 expression and the amount of free fatty acids in epidermal keratinocytes. METHODS: We examined whether MVL increases ABCA12 mRNA and protein levels and the amount of Nile red‐positive lipids in cultured epidermal keratinocytes and in a three‐dimensional epidermal model by cell staining. Promotion of fatty acid production by MVL was analyzed by liquid chromatography‐mass spectrometry. We also evaluated whether MVL addition increases PPAR β/δ mRNA expression in cultured keratinocytes. Based on the results, a randomized controlled trial was conducted in which milky lotions containing MVL and placebo were applied to dry facial skin of healthy female volunteers in winter. RESULTS: MVL increased ABCA12 mRNA and protein levels and lamellar granule number and size. Fatty acid analysis revealed that MVL elevated myristic acid, palmitic acid, and palmitoleic acid levels as well as PPAR β/δ mRNA expression. In human tests, milky lotions containing MVL were shown to significantly improve transepidermal water loss (TEWL) in the stratum corneum compared to placebo. CONCLUSION: The results suggest that MVL increases fatty acid uptake and ABCA12, promotes fatty acid transport to lamellar granules, and improves epidermal barrier function in dry skin through increased expression of PPAR β/δ.