title: Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats.
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.
authors: School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia.
authors: Abishek
authors: A
authors: Iyer
authors: Kathleen
authors: K
authors: Kauter
authors: Md Ashraful
authors: MA
authors: Alam
authors: Sung Hee
authors: SH
authors: Hwang
authors: Christophe
authors: C
authors: Morisseau
authors: Bruce D
authors: BD
authors: Hammock
authors: Lindsay
authors: L
authors: Brown
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001565:Benzoates / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D002319:Cardiovascular System / Q000473:pathology / Q000503:physiopathology; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D010179:Pancreas / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C524106:4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid; D001565:Benzoates; D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004791:Enzyme Inhibitors; D008055:Lipids; D014508:Urea; D004851:Epoxide Hydrolases