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J Diabetes. 2016 May;8(3):305-13. doi: 10.1111/1753-0407.12358. Epub 2016 Jan 9.

Soluble epoxide hydrolase: A potential target for metabolic diseases.

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Collaborative Innovation Center of Tianjin for Medical Epigenetics, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China.


Epoxyeicosatrienoic acids (EETs), important lipid mediators derived from arachidonic acid, have many beneficial effects in metabolic diseases, including atherosclerosis, hypertension, cardiac hypertrophy, diabetes, non-alcoholic fatty liver disease, and kidney disease. Epoxyeicosatrienoic acids can be further hydrolyzed to less active diols by the enzyme soluble epoxide hydrolase (sEH). Increasing evidence suggests that inhibition of sEH increases levels of EETs, which have anti-inflammatory effects and can prevent the development of hypertension, atherosclerosis, heart failure, fatty liver, and multiple organ fibrosis. Arachidonic acid is the most abundant omega-6 polyunsaturated fatty acid (PUFA) and shares the same set of enzymes with omega-3 PUFAs, such as docosahexaenoic acid and eicosapentaenoic acid. The omega-3 PUFAs and metabolites, such as regioisomeric epoxyeicosatetraenoic acids and epoxydocosapentaenoic acids, have been reported to have strong vasodilatory and anti-inflammatory effects. Therefore, sEH may be a potential therapeutic target for metabolic disorders. In this review, we focus on our and other recent studies of the functions of sEH, including the effects of its eicosanoid products from both omega-3 and omega-6 PUFAs, in various metabolic diseases. We also discuss the possible cellular and molecular mechanisms underlying the regulation of sEH.


arachidonic acid; epoxyeicosatrienoic acids; metabolic disease; polyunsaturated fatty acids; soluble epoxide hydrolase; 代谢性疾病; 可溶性表氧化物水解酶; 多不饱和脂肪酸; 环氧-二十碳三烯酸; 花生四烯酸

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