Omega-3 fatty acid supplementation influences the whole blood transcriptome in women with obesity, associated with pro-resolving lipid mediator production

• Supplementation for 3 months resulted in higher levels of DHA and EPA in plasma PC.
• n-3 PUFA supplementation increased pro-resolving lipid mediator production.
• n-3 PUFA supplementation decreased proinflammatory marker concentrations.
• n-3 PUFA supplementation led to decrease fasting TG and insulin.
• Resolvins through activity of NF-κB, PPAR-α NRF2 influenced gene expression.

The n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce low-grade inflammation associated with obesity. The relationship between therapeutic response to n-3 PUFAs and modification of the transcriptome in obesity or metabolic syndrome remains to be explored.Blood samples were obtained from women with obesity before and after three-months supplementation with a moderate dose of n-3 PUFAs (1.8 g EPA + DHA per day) or from controls. n-3 PUFAs (GC) and plasma concentrations of lipoxins, resolvins, protectin X (GC–MS/MS) and inflammatory markers (ELISA) were measured. Whole blood transcriptome was assayed using microarray.Women supplemented with n-3 PUFAs for 3 months had significantly higher levels of EPA and DHA in plasma phosphatidylcholine. n-3 PUFA supplementation, in contrast to placebo, significantly decreased the concentrations of several inflammatory markers (SELE, MCP-1, sVCAM-1, sPECAM-1, and hsCRP), fasting triglycerides and insulin and increased the concentrations of pro-resolving DHA derivatives in plasma. The microarray data demonstrated effects of n-3 PUFAs on PPAR-α, NRF2 and NF-κB target genes.N-3 PUFAs increased DHA-derived pro-resolving mediators in women with obesity. Elevated resolvins and up-regulation of the resolvin receptor occurred in parallel with activation of PPAR-α target genes related to lipid metabolism and of NRF2 up-regulated antioxidant enzymes.