Our study has shed new light on the mechanisms underlying the anti-obesity effects of n-3 PUFAs by demonstrating that their downstream epoxide metabolites, 17,18-EEQ and 19,20-EDP, when combined with t-TUCB, had similar regulatory effects on energy expenditure, thermogenesis, and glucose and lipid metabolism accompanied by changes in gene expression of Pgc1α and Ucp1. Here, UCP1 is linked to obesity due to melanocortin 4 receptor deficiency.