Comparison of the dietary omega-3 fatty acids impact on murine psoriasis-like skin inflammation and associated lipid dysfunction

Persistent skin inflammation and impaired resolution are the main contributors to psoriasis and associated cardiometabolic complications. Omega-3 fatty acids (FA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to exert beneficial effects on inflammatory response and lipid function. However, a specific role in psoriasis disease and accompanied pathological mechanisms are still a matter of debate. Here, we aimed to perform a direct comparison between EPA and DHA diet treatment for 12 weeks of psoriasis-like skin inflammation in the K14-Rac1V12 mouse model. By utilizing sensitive high throughput techniques, we targeted EPA- and DHA-derived specialized pro-resolving mediators (SPMs) and identified tightly connected signaling pathways by RNA sequencing. Treatment with experimental diets significantly decreased circulating pro-inflammatory cytokines and plasma lipids, altered psoriasis macrophages phenotype and affected genes of atherosclerosis related pathways. The superficial role of these changes was related to DHA treatment and included skin abundance in resolvin D5, protectin X and maresin 2. EPA treated mice expressed less pronounced effects but resulted in decreasing skin accumulation of prostaglandin E2 and thromboxane B2. These results indicate that altering psoriasis with the omega-3 FA might have clinical significance and DHA treatment should be considered over EPA in this specific population. Overall design: Comparison of 3 experimental diets treatment in K14-Rac1 psoriasis mouse model