33261 Topically applied skin natural fatty acids and 12-hydroxystearic acid boosts barrier lipids

Abstract

When properly formulated into lotions and cleansers to enable deposition and delivery into skin it has been previously shown that skin-natural fatty acids (palmitic acid and stearic acid) elongate into longer chain fatty acids and ceramides which are critical for skin barrier health. In separate studies, 12-hydroxystearic acid (12-HSA) has been shown to act as a PPAR agonist to help with epidermal homeostasis and barrier function. Exploring potential synergy between topically applied skin-natural fatty acids and 12-HSA is of interest to understand mechanisms for improving barrier health and develop more efficacious products. To determine if 12-HSA, applied topically with deuterated palmitic acid (C16:0), promotes its elongation and integration into skin ceramides and sphingosine. Monolayer keratinocytes were dosed with 1 uM of deuterated palmitic acid and varying levels of 12-HSA for 7 days prior to cell harvesting and lipid extraction. Ex vivo human skin explants were dosed topically with 3% deuterated palmitic acid, with or without 3% 12-HSA, for 5 days prior to lipid extraction. Analysis was conducted by LC/MS/MS. Deuterated fatty acids with chain lengths higher than palmitic were detected in each of the combinations of palmitic acid and 12-HSA tested in keratinocytes. Correspondingly, 12-HSA boosted levels of deuterated longer chain fatty acids in skin explants compared with the controls without 12-HSA and increased integration of deuterated palmitic acid into ceramides. Topical application of 12-HSA and skin-natural fatty acids show synergistic metabolic effect by enhancing lipid elongation and ceramide production, consistent with building and supporting a healthy barrier.