Metabolomics Elucidates Dose-Dependent Molecular Beneficial Effects of Hesperidin Supplementation in Rats Fed an Obesogenic Diet
Metabolomics Elucidates Dose-Dependent Molecular Beneficial Effects of Hesperidin Supplementation in Rats Fed an Obesogenic Diet
复制标题
DOI：
10.3390/antiox9010079
复制
发表时间：
2020-01-01
期刊：
影响因子：
7
通讯作者：
Mayneris-Perxachs, Jordi
中科院分区：
文献类型：
--
作者：
Guirro, Maria;Gual-Grau, Andreu;Mayneris-Perxachs, Jordi
代谢综合征(METS)是一种全球性的流行病。多酚被认为是预防该病的良好候选物质，尽管其机制尚不完全清楚。肠道微生物区系似乎在多酚的有益作用中起着关键作用。在这里，我们评估了柑橘多酚橙皮苷结合非靶向代谢组学方法的效果，该方法具有阐明宿主-微生物组相互作用的内在潜力，具有广泛的人体测量学和生化特征，并将代谢组学结果与我们之前的16S rRNA细菌测序数据相结合。这些大鼠被喂以标准或肥胖的自助餐厅饮食(CAF)，为期17周。9周后，大鼠补充赋形剂；低(H1)或高(H2)橙皮苷剂量。CAF动物发展了METS特征。在CAF大鼠中补充橙皮苷可降低总胆固醇、低密度脂蛋白胆固醇和游离脂肪酸。最高剂量的橙皮苷还可以改善血压、胰岛素敏感性，并降低动脉僵硬和炎症的标志物。代谢组学显示，脂类成分得到改善，循环氨基酸减少，炎症和氧化应激相关代谢物的排泄减少。类杆菌科细菌在CAF-H2组中的增加与微生物衍生代谢物的更高排泄相平行。总体而言，我们的结果为橙皮苷对蛋氨酸的分子效应提供了详细的见解，并表明它是一种很有前途的益生素，用于治疗甲硫氨酸和相关疾病。
Metabolic syndrome (MetS) is a global epidemic concern. Polyphenols are proposed as good candidates for its prevention, although their mechanisms are not fully understood. The gut microbiota seems to play a key role in polyphenol beneficial effects. Here, we assessed the effects of the citrus polyphenol hesperidin combining an untargeted metabolomics approach, which has an inherent potential to elucidate the host-microbiome interplay, with extensive anthropometric and biochemical characterizations and integrating metabolomics results with our previous 16S rRNA bacterial sequencing data. The rats were fed either a standard or an obesogenic cafeteria diet (CAF) for 17 weeks. After nine weeks, rats were supplemented with vehicle; low- (H1), or high- (H2) hesperidin doses. CAF animals developed MetS features. Hesperidin supplementation in CAF rats decreased the total cholesterol, LDL-C, and free fatty acids. The highest hesperidin dose also ameliorated blood pressure, insulin sensitivity, and decreased markers of arterial stiffness and inflammation. Metabolomics revealed an improvement of the lipidomic profile, decreases in circulating amino acids, and lower excretions of inflammation- and oxidative stress-related metabolites. Bacteroidaceae increases in the CAF-H2 group paralleled higher excretions of microbial-derived metabolites. Overall, our results provide detailed insights into the molecular effects of hesperidin on MetS and suggest that it is a promising prebiotic for the treatment of MetS and related conditions.