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

Abishek Iyer, Kathleen Kauter, Md Ashraful Alam, Sung Hee Hwang, Christophe Morisseau, Bruce D. Hammock, Lindsay Brown

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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.

Original languageEnglish (US)
Article number758614
JournalExperimental Diabetes Research
Volume2012
DOIs
StatePublished - 2012

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ASJC Scopus subject areas

  • Medicine(all)
  • Endocrinology, Diabetes and Metabolism
  • Music

Cite this

Iyer, A., Kauter, K., Alam, M. A., Hwang, S. H., Morisseau, C., Hammock, B. D., & Brown, L. (2012). Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats. Experimental Diabetes Research, 2012, [758614]. https://doi.org/10.1155/2012/758614