Peroxisomal fatty acid oxidation and glycolysis are triggered in mouse models of lesional atopic dermatitis.

Abstract

Abstract Alterations of the lipid profile of the stratum corneum have an important role in the pathogenesis of atopic dermatitis (AD) because they contribute to epidermal barrier impairment. However, they have not previously been envisioned as a cellular response to altered metabolic requirements in AD epidermis. Here, we report that the lipid composition in the epidermis of flaky tail (ft/ft) mice mimics that of human lesional AD (ADL), both showing a shift towards shorter lipid species. The amounts of C24 and C26 free fatty acids and C24- and C26-ceramides — oxidized exclusively in peroxisomes — were reduced in ft/ft epidermis despite increased lipid synthesis, similar to human ADL. Increased ACOX1 protein and activity in granular keratinocytes of ft/ft epidermis, altered lipid profile in human epidermal equivalents overexpressing ACOX1 and increased ACOX1 immunostaining in skin biopsies from ADL patients suggest that peroxisomal β-oxidation significantly contributes to lipid signature in ADL epidermis. Moreover, we show that increased anaerobic glycolysis in ft/ft mouse epidermis is essential for keratinocyte proliferation and ATP synthesis, but does not contribute to local inflammation. Thus, this work evidenced a metabolic shift towards enhanced peroxisomal β-oxidation and anaerobic glycolysis in ADL epidermis.