Considering the relevance of sEH for inflammation, cardiovascular disorders, potential lipid abnormalities, and regulation in adipose tissue, we investigated the role of sEH in HF-diet–induced lipid abnormalities and the associated changes in liver by treatment with sEH inhibition, gene knockout or overexpression with recombinant human sEH in mice. The gene discussed is EPHX2; the disease is hydrops fetalis.