Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats

Iyer, Abishek and Kauter, Kathleen and Alam, Md. Ashraful and Hwang, Sung Hee and Morisseau, Christophe and Hammock, Bruce D. and Brown, Lindsay (2012) Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats. Experimental Diabetes Research, 2012. pp. 1-11. ISSN 1687-5214

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Abstract

The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral adipose deposition, hyperglycaemia, glucose and insulin intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH) during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndrome in vivo including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. The present study describes the pharmacological responses to this selective sEH inhibitor in rats with the signs of diet-induced metabolic syndrome.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Copyright © 2012 Abishek Iyer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Depositing User: Professor Lindsay Brown
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 07 Feb 2012 07:14
Last Modified: 27 Aug 2014 23:03
Uncontrolled Keywords: metabolic syndrome; hypertension; obesity
Fields of Research (FOR2008): 11 Medical and Health Sciences > 1101 Medical Biochemistry and Metabolomics > 110107 Metabolic Medicine
06 Biological Sciences > 0606 Physiology > 060699 Physiology not elsewhere classified
11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111504 Pharmaceutical Sciences
Socio-Economic Objective (SEO2008): C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920104 Diabetes
Identification Number or DOI: doi: 10.1155/2012/758614
URI: http://eprints.usq.edu.au/id/eprint/19935

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