Skin inflammation and impaired adipogenesis in a mouse model of acid ceramidase deficiency

• DOI: 10.1002/jimd.12552
• Publication Date: 2022-09-09T21:15:57Z
• Authors: Jitka Rybova; Ladislav Kuchar; Jakub Sikora; William M. McKillop; Jeffrey A. Medin
• Keywords: Sphingolipid; Lipid droplet

Abstract Acid ceramidase catalyzes the degradation of ceramide into sphingosine and a free fatty acid. deficiency results in lipid accumulation many tissues leads to development Farber disease (FD). Typical manifestations classical FD include formation subcutaneous nodules joint contractures as well hoarse voice. Healthy skin depends on unique profile form barrier that confers protection from pathogens, prevents excessive water loss, mediates cell–cell communication. Ceramides comprise ~50% total epidermis lipids regulate cutaneous homeostasis inflammation. Abnormal including visual lesions has been reported patients, but detailed study not performed. We conducted pathophysiological our mouse model FD. observed altered composition dominated by all studied species buildup abnormal storage structures affecting mainly dermis. A acid activity also led activation inflammatory IL‐6/JAK/signal transducer activator transcription 3 noncanonical NF‐κB signaling pathways. Last, we report reduced proliferation fibroblasts adipose‐derived stem/stromal cells (ASC) along with impaired differentiation ASCs mature adipocytes.