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

持续性皮肤炎症及炎症消退受损是银屑病（psoriasis）及其伴随的心血管代谢并发症的主要致病因素。已知ω-3脂肪酸（Omega-3 fatty acids, FA）、二十碳五烯酸（EPA）及二十二碳六烯酸（DHA）可对炎症反应与脂质功能发挥有益作用。然而，其在银屑病发病及伴随病理机制中的特定作用仍存在争议。本研究旨在针对K14-Rac1V12小鼠模型中的类银屑病皮肤炎症，对比EPA与DHA膳食干预12周的效果。本研究借助高灵敏度高通量技术，靶向检测EPA与DHA衍生的专门促消退介质（specialized pro-resolving mediators, SPMs），并通过RNA测序（RNA sequencing）鉴定出紧密关联的信号通路。实验膳食干预可显著降低循环促炎细胞因子与血浆脂质水平，改变银屑病相关巨噬细胞表型，并调控动脉粥样硬化相关通路的基因表达。上述变化的皮肤层面效应与DHA干预相关，具体体现为皮肤中消退素D5、保护素X及马雷斯菌素2的丰度升高。EPA干预小鼠的效应则相对较弱，但可降低皮肤中前列腺素E2与血栓素B2的蓄积量。上述结果表明，通过ω-3脂肪酸干预银屑病或具有临床价值，且针对该特定人群，应优先考虑DHA干预而非EPA。实验设计：在K14-Rac1银屑病小鼠模型中对比3种实验膳食的干预效果。