Metabolic syndrome (MetS) represents a group of abnormalities that enhances the risk for cardiovascular disease, diabetes and stroke. The Mediterranean diet seems to be an important dietary pattern, which reduces the incidence of MetS. Hydroxytyrosol (HT) - a simple phenol found in olive oil - has received increased attention for its antioxidant activity. Recently, the European Foods Safety Authority (EFSA) claimed that dietary consumption of HT exhibits a protective role against cardiovascular disease. In this study, an experimental protocol has been setup, including isolated HT administration in a diet induced model of MetS in young Wistar rats, in order to find out whether HT has a protective effect against MetS. Rats were randomly divided into two groups nurtured by high-carbohydrate high-fat (H) (MetS inducing diet) and high-carbohydrate high-fat + HT (HHT). HT (20 mg/kg/d oral gavage, water vehicle) was administered for 8 weeks on the basal diet. Previous pharmacological evaluation of HT showed that hepatic steatosis was reduced and the inflammatory cells into the liver were infiltrated. These indicate that HT shows bioactivity against metabolic syndrome. Therefore, the metabolomics evaluation of liver extracts would indicate the putative biochemical mechanisms of HT activity. Thus, the extracts of liver tissues were analyzed using Ultra Performance Liquid Chromatography – High Resolution Mass Spectrometry (UPLC-HRMS, Orbitrap Discovery) and Nuclear Magnetic Resonance (NMR) spectroscopy (Bruker Avance III 600 MHz). Multivariate analysis was performed in order to gain insight on the metabolic effects of HT administration on the liver metabolome. Normalization employing multiple internal standards and Quality Control–based Robust LOESS (LOcally Estimated Scatterplot Smoothing) Signal Correction algorithm (QC-RLSC) was added in the processing pipeline to enhance the reliability of metabolomic analysis by reducing unwanted information. Experimentally, HHT rats were clearly distinguished from H in PLS-DA, showing differences in the liver metabolome between the groups and specific biomarkers were determined supporting the pharmacological findings. More specifically, HT has shown to be effective towards the mobilization of lipids as various lipid classes being differentially regulated between the H and HHT groups. Interestingly branched fatty acid esters of hydroxy oleic acids (OAHSA) lipids have been shown to be up regulated to the HHT group, denoting the alleviation of the MetS to the animals administered with HT.

代谢综合症（MetS）代表一组异常现象，会增加罹患心血管疾病，糖尿病和中风的风险。地中海饮食似乎是一种重要的饮食模式，可减少MetS的发生。羟基酪醇（HT）-一种在橄榄油中发现的简单酚-由于其抗氧化活性而受到越来越多的关注。最近，欧洲食品安全局（EFSA）声称，饮食中摄入HT对心血管疾病具有保护作用。在这项研究中，已经建立了实验方案，包括在年轻的Wistar大鼠的饮食诱导的MetS模型中单独给予HT，以了解HT是否对MetS具有保护作用。将大鼠随机分为两组，分别以高碳水化合物高脂（H）（MetS诱导饮食）和高碳水化合物高脂+ HT（HHT）培养。在基础饮食上给予HT（20 mg / kg / d口服强饲法，水媒）。先前对HT的药理评估表明，肝脂肪变性减少，并且进入肝脏的炎性细胞浸润。这些表明HT显示出对代谢综合症的生物活性。因此，肝提取物的代谢组学评估将表明HT活性的推测生化机制。因此，使用超高效液相色谱-高分辨率质谱（UPLC-HRMS，Orbitrap Discovery）和核磁共振（NMR）光谱（Bruker Avance III 600 MHz）分析了肝组织的提取物。进行多变量分析以了解HT给药对肝脏代谢组的代谢作用。在处理管道中添加了采用多个内部标准和基于质量控制的鲁棒LOESS（局部估计散点图平滑）信号校正算法（QC-RLSC）的标准化，以通过减少不需要的信息来增强代谢组学分析的可靠性。实验上，HHT大鼠在PLS-DA中与H明显不同，表明各组之间肝脏代谢组之间的差异，确定了特定的生物标志物以支持药理学发现。更具体地，HT已经显示出对脂质的动员有效，因为在H和HHT基团之间不同的脂质类别被不同地调节。