Epidermal Lipids: Key Mediators of Atopic Dermatitis Pathogenesis

Abstract

Skin barrier keeps the "inside-in" and the "outside-out" forming a protective blanket against external insults. Epidermal lipids such as ceramides, fatty acids, triglycerides and cholesterol are integral components in driving the formation and maintenance of epidermal permeability barrier (EPB). A breach in this lipid barrier sets the platform for the subsequent onset and progression of atopic dermatitis (AD). Such lipids are also important in the normal functioning of different organisms, both plants and animals and in diseases including cancer. A double increase in AD rate in the recent years and the chronic nature of this disorder emphasizes the need of this review to shed light on the multifaceted role of the diverse types of lipids in mediating AD pathogenesis.

Epidermal mammalian target of rapamycin complex 2 controls lipid synthesis and filaggrin processing in epidermal barrier formation

“…However, although it is widely accepted that epidermal lipids are integral components driving the formation and maintenance of the epidermal permeability barrier, the exact mechanistic link how epidermal lipids regulate epidermal barrier function and/or vice versa, is not entirely resolved. 59,60 Therefore, although our findings in Ric EKO mice suggest that the quantitative and qualitative perturbations in lipid composition is causative for the observed skin barrier defect in Ric EKO mice, at this stage, we cannot exclude the possibility that perturbed epidermal architecture contributes to perturbed lipid synthesis. 59,60 It will be of interest to investigate in future studies additional downstream mediators of mTORC2 signaling to understand how epidermal de novo lipogenesis and SC lipid homeostasis is regulated by mTORC2.…”

Topical Pioglitazone Nanoformulation for the Treatment of Atopic Dermatitis: Design, Characterization and Efficacy in Hairless Mouse Model

“…AD is characterized by having a defective or weakened epidermal barrier and lipid abnormalities that promote an increase in TEWL and a decline in SCH. Therefore, the noninvasive assessment of these biophysical parameters is successfully utilized to analyze the skin barrier function in patients with AD [37,38]. In this study, repeated application of oxazolone significantly increased TEWL and reduced SCH, indicating disruption of the epidermal permeability barrier.…”

Lipidomics profiling of skin surface lipids in senile pruritus

“…Cer-EOS and Cer-NS are the two main subclasses of Cers. These Cers are related to the formation of the corneocyte lipid envelope in the SC and play a crucial role in formation of an intact epidermal permeability barrier [23]. In the present study, the relationships between Cers and skin barrier function were determined by Pearson's correlation analysis.…”