TY - JOUR
T1 - EETs/sEH in diabetes and obesity-induced cardiovascular diseases
AU - Huang, Hui
AU - Weng, Jing
AU - Wang, Mong-Heng
N1 - Funding Information:
Part of the work described in this review was supported by NSFC ( 81422011 , 81370837 , and 81170647 ) to H. Huang and an American Heart Association Grant-in-Aid Grant ( AHASE 00090 ) to M. H. Wang.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - Cytochrome P450
KW - Diabetes
KW - Eicosanoids
KW - Obesity
KW - Soluble epoxide hydrolase
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U2 - 10.1016/j.prostaglandins.2016.05.004
DO - 10.1016/j.prostaglandins.2016.05.004
M3 - Review article
C2 - 27184755
AN - SCOPUS:84970028145
SN - 1098-8823
VL - 125
SP - 80
EP - 89
JO - Prostaglandins and Other Lipid Mediators
JF - Prostaglandins and Other Lipid Mediators
ER -