N-3 Polyunsaturated Fatty Acids and Inflammation in Obesity: Local Effect and Systemic Benefit

Figure 3

Putative mechanism by which adipose tissue mediates the systemic benefits derived from n-3 PUFA consumption. N-3 PUFA reduces adipose tissue inflammation via changing membrane phospholipid composition and activity of signaling pathways. The manipulation of membrane phospholipids composition and lipid raft microdomain with n-3 PUFA modify downstream processes mediated by membrane, such as signaling transduction, gene expression, and eicosanoid biosynthesis. Increased biosynthesis of resolvin and protectin contributes to resolution process. PPARγ activation mediated by n-3 PUFA leads to increased number of small adipocytes, M2 macrophages, and Treg cells, while normalizing secretory function featured by induced adiponectin synthesis, inhibited lipolysis, and reduced pro-inflammatory mediator secretion. As anticipated, NF-κB inhibition, which is partly dependent on PPARγ activation, downregulates the expression of proinflammatory gene directly and indirectly via determining the differentiation of monocytes. GPR120 is the functional receptor making response to n-3 PUFA and mediates the anti-inflammatory benefits by repressing several inflammatory signalings. The improved storage and secretory functions of adipose tissue lead to relief of AT-specific inflammation, followed by global improvement of metabolic profile. Adipose-specific blunting of inflammation primarily favors the functional improvement of several organ systems involving liver, skeletal muscle, and brain.