title: EETs/sEH in diabetes and obesity-induced cardiovascular diseases.
abstract: Despite the optimization of blood glucose control and the therapeutic management of risk factors, obesity- and diabetes-induced cardiovascular diseases are still major health problems in the United States. Arachidonic acid (AA), an endogenous 20-carbon polyunsaturated fatty acid, is metabolized by cytochrome P450 (CYP) epoxygenases into epoxyeicosatrienoic acids (EETs), which are important lipid mediators with many beneficial effects in type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and obesity- and diabetes-induced cardiovascular diseases. EETs can be further metabolized to less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). It has been demonstrated that the use of sEH blockers, which prevent EET degradation, is a promising pharmacological approach to promoting insulin secretion, preventing endothelial dysfunction, decreasing blood pressure, and protecting against target organ damage in obesity and metabolic diseases. This review will focus on biochemistry of CYP monooxygenase system as well as the pharmacology and physiological significance of EETs and sEH. We will also discuss the role of EETs/sEH in T1DM, T2DM, and obesity- and diabetes-induced cardiovascular diseases.
authors.affiliation: Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China; Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Physiology, Augusta University, Augusta, GA 30912, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Weng
authors.affiliation: Department of Physiology, Augusta University, Augusta, GA 30912, United States. Electronic address: mwang@augusta.edu.
authors.forename: Mong-Heng
authors.initials: MH
authors.lastname: Wang
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism*; D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000201:enzymology / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009765:Obesity / Q000150:complications*; D012995:Solubility
chemical_list: D004851:Epoxide Hydrolases; D015126:8,11,14-Eicosatrienoic Acid
keywords: Cytochrome P450; Diabetes; Eicosanoids; Obesity; Soluble epoxide hydrolase