Hydroxytyrosol ameliorates metabolic, cardiovascular and liver changes in a rat model of diet-induced metabolic syndrome: pharmacological and metabolism-based investigation

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 cardioprotectionby 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 treatmentwith HT (20 mg/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 andresultant diastolic stiffness and reduced markers of liver damage in a diet-induced rat model of metabolicsyndrome. These results were accompanied by reduced infiltration of monocytes/macrophages into theheart with reduced biomarkers of oxidative stress. Furthermore, in an HRMS-based metabolism study ofHT, 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. Theseresults provide direct evidence for cardioprotective effects of hydroxytyrosol by attenuation of metabolicrisk factors. The implications of altered metabolism of HT in high-carbohydrate, high-fat diet fed obeserats warrant further investigation