title: Hydroxytyrosol ameliorates metabolic, cardiovascular and liver changes in a rat model of diet-induced metabolic syndrome: Pharmacological and metabolism-based investigation.
abstract: Metabolic syndrome is a clustering of interrelated risk factors for cardiovascular disease and diabetes. The Mediterranean diet has been proposed as an important dietary pattern to confer cardioprotection by attenuating risk factors of metabolic syndrome. Hydroxytyrosol (HT) is present in olive fruit and oil, which are basic constituents of the Mediterranean diet. In this study, we have shown that treatment with HT (20mg/kg/d for 8 weeks) decreased adiposity, improved impaired glucose and insulin tolerance, improved endothelial function with lower systolic blood pressure, decreased left ventricular fibrosis and resultant diastolic stiffness and reduced markers of liver damage in a diet-induced rat model of metabolic syndrome. These results were accompanied by reduced infiltration of monocytes/macrophages into the heart with reduced biomarkers of oxidative stress. Furthermore, in an HRMS-based metabolism study of HT, we have identified 24 HT phase I and II metabolites, six of them being over-produced in high-starch, low-fat diet fed rats treated with HT compared to obese rats on high-carbohydrate, high-fat diet. These results provide direct evidence for cardioprotective effects of hydroxytyrosol by attenuation of metabolic risk factors. The implications of altered metabolism of HT in high-carbohydrate, high-fat diet fed obese rats warrant further investigation.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, The Hakubi Centre for Advanced Research, Kyoto University, Kyoto, Japan; School of Health and Wellbeing, University of Southern Queensland, Toowoomba 4350, Australia.
authors.forename: Hemant
authors.initials: H
authors.lastname: Poudyal
authors.affiliation: Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Lemonakis
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Efentakis
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Gikas
authors.affiliation: Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Halabalaki
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Andreadou
authors.affiliation: Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, 15771, Greece. Electronic address: skaltsounis@pharm.uoa.gr.
authors.forename: Leandros
authors.initials: L
authors.lastname: Skaltsounis
authors.affiliation: School of Health and Wellbeing, University of Southern Queensland, Toowoomba 4350, Australia. Electronic address: Lindsay.Brown@usq.edu.au.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Brown
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004040:Dietary Carbohydrates / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D004040:Dietary Carbohydrates; D004041:Dietary Fats; C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol
keywords: Cardiovascular; Hydroxytyrosol; Metabolic syndrome; Obesity; Olive oil; Olives