981 Adiponectin downregulation in lesional skin contributes to enhanced mTORC1 activation and skin inflammation in rosacea

Rosacea is a chronic inflammatory skin disease whose pathogenesis is poorly understood. Adiponectin plays a critical role in maintenance of metabolic homeostasis. In recent years, accumulating evidence indicates rosacea development is associated with metabolic abnormalities. Here, we demonstrated the expression of adiponectin is reduced in skin lesion of patients with rosacea. Rosacea associated cyto-chemokines produced from keratinocytes downregulated production and secretion of adiponectin from primary subcutaneous adipocytes. Interestingly, we observed adiponectin deficiency aggravates rosacea-like dermatitis in mouse model. These findings implicate adiponectin level reduction and rosacea inflammation form vicious cycle. Mechanistically, activation of mTORc1 signaling by cathelicidin treatment in keratinocyte was suppressed by adiponectin. Furthermore, we exhibited intraperitoneal supplementation of adiponectin, and transdermally deliverable adiponectin receptor 1 agonist application improves the skin inflammation in mouse rosacea-like model. Thus, we validated a role of adiponectin in the pathogenesis of rosacea and formulated a rationale for the use of adiponectin’s biological effect in the treatment of rosacea.