Metabolomics study of hydroxytyrosol's administration in a metabolic syndrome rat model

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 a single phenol present in large amount in olive byproducts and in lower amounts in olive oil and in olive fruits, which are basic constituents of the Mediterranean diet. In the context of identifying the features of HT that are responsible for its effects on the metabolic syndrome, an experimental protocol has been setup encompassing isolated HT administration in a diet induced model of metabolic syndrome in young Wistar rats. Rats were randomly divided into four groups as cornstarch (CS), cornstarch + HT (CSHT), high-carbohydrate high-fat (HF) and high-carbohydrate high-fat + HT (HFHT) (n = 6/group). HT (20 mg/kg/d oral gavage, water vehicle) was administered for 8 weeks on the basal diet (CS or HF). In order to gain insight on the metabolic effects of HT administration on the total biochemical profile (metabolome), an untargeted approach (metabolomics) has been developed and attempted on the rat plasma and urine samples from the metabolic syndrome model. The new biomarkers discovered from multivariate analysis have been identified by comparison with public domain metabolome libraries but also by confirmation using HRMS/MS, highlighting the differences in the biochemistry of HFHT animals versus controls as well as versus CSHT. Fatty acid metabolism was found to be down regulated in HFHT rats while glycerol, which releases from triacylglycerols, was the main up regulated metabolite in HFHT rats and correlates to fatty acid transportation catabolism. HT supplementation for 8 weeks reduced visceral obesity and was associated with improved left ventricular structure and function, reduced blood pressure, improved glucose disposal and reduced hepatic steatosis.

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