Hydroxytyrosol ameliorates metabolic, cardiovascular and liver changes in a rat model of diet-induced metabolic syndrome: Pharmacological and metabolism-based investigation
Hydroxytyrosol ameliorates metabolic, cardiovascular and liver changes in a rat model of diet-induced metabolic syndrome: Pharmacological and metabolism-based investigation
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DOI：
10.1016/j.phrs.2016.12.002
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发表时间：
2017-03-01
影响因子：
9.3
通讯作者：
Brown, Lindsay
中科院分区：
文献类型：
--
作者：
Poudyal, Hemant;Lemonakis, Nikolaos;Brown, Lindsay
代谢综合征是心血管疾病和糖尿病相关危险因素的聚类。地中海饮食被认为是一种重要的饮食模式，可以通过降低代谢综合征的危险因素来保护心脏。羟基酪醇（HT）存在于橄榄果实和橄榄油中，它们是地中海饮食的基本成分。在这项研究中，我们已经证明，在饮食诱导的代谢综合征大鼠模型中，HT治疗（20 mg/kg/d，持续8周）可以减少肥胖，改善葡萄糖和胰岛素耐量受损，改善内皮功能，降低收缩压，减少左心室纤维化和由此产生的舒张僵硬，减少肝损伤标志物。这些结果伴随着单核细胞/巨噬细胞向心脏的浸润减少，氧化应激的生物标志物减少。此外，在一项基于hrms的羟色胺代谢研究中，我们发现了24种羟色胺I期和II期代谢物，与高碳水化合物、高脂肪饮食的肥胖大鼠相比，高淀粉、低脂饮食喂养的大鼠羟色胺过量产生了其中的6种。这些结果为羟基酪醇通过降低代谢危险因素而具有心脏保护作用提供了直接证据。高碳水化合物、高脂肪饮食喂养的肥胖大鼠体内激素代谢改变的意义值得进一步研究。(C) 2016 Elsevier Ltd.版权所有。
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 (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 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. (C) 2016 Elsevier Ltd. All rights reserved.