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Excess energy intake can trigger an uncontrolled inflammatory response, leading to systemic low-grade inflammation and metabolic disturbances that are hypothesised to contribute to cardiovascular disease and type 2 diabetes. The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are suggested to mitigate this inflammatoryresponse,butthemechanismsareunclear,especiallyatthetissuelevel. Adiposetissues, the first tissues to give an inflammatory response, may be an important target site of action for EPA and DHA. To evaluate the effects of EPA and DHA in white and brown adipose tissues, we fed male C57Bl/6J mice either a high fat diet (HFD) with 5% corn oil, an HFD with 40% of the corn oil substituted for purified EPA and DHA triglycerides (HFD-ED), or normal chow, for 8 weeks. Fatty acid profiling and transcriptomics were used to study how EPA and DHA affect retroperitoneal whiteandbrownadiposetissues. HFD-EDfedmiceshowedreducedlipidaccumulationandlevelsof the pro-inflammatory fatty acid arachidonic acid in both white and brown adipose tissues, compared withHFD-cornoilfedanimals. Thetranscriptomicanalysisshowedchangesinβ-oxidationpathways, supporting the decreased lipid accumulation in the HFD-ED fed mice. Therefore, our data suggests that EPA and DHA supplementation of a high fat diet may be anti-inflammatory, as well as reduce lipid accumulation in adipose tissues.