Comparative Modulation of Immune Responses and Inflammation by n-6 and n-3 Polyunsaturated Fatty Acids in Oxylipin-Mediated Pathways

Our study investigates the comparative effects of n-6 and n-3 polyunsaturated fatty acids (PUFAs) on immune modulation and inflammation using a fat-1 transgenic mouse model capable of endogenously converting n-6 PUFAs to n-3 PUFAs. The results show that n-6 PUFAs, particularly arachidonic acid (AA), promote a pro-inflammatory environment by increasing the production of inflammatory mediators, including leukotrienes and prostaglandins, while upregulating NFκB signaling and NLRP3 inflammasome activation. In contrast, n-3 PUFAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exhibit anti-inflammatory and pro-resolving properties by enhancing the production of resolvins, protectins, and maresins, and upregulating PPARα expression. Quantitatively, n-3 PUFAs led to a 4-fold increase in resolvin levels compared to the n-6 group (p < 0.001), promoting a resolution of inflammation. This study underscores the critical importance of maintaining an optimal balance between n-6 and n-3 PUFAs in the diet to prevent chronic inflammation and suggests that increasing dietary n-3 PUFAs may mitigate inflammation-driven diseases. The findings highlight the need for further research into the optimal dietary ratios of n-6 and n-3 PUFAs for immune health and disease prevention.