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Open AccessArticle

Metabolomics Elucidates Dose-Dependent Molecular Beneficial Effects of Hesperidin Supplementation in Rats Fed an Obesogenic Diet

1
Eurecat, Centre Tecnològic de Catalunya, Technological Unit of Omics Sciences, 43204 Reus, Spain
2
Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili. Marcel.lí Domingo, 1, 43007 Tarragona, Spain
3
Eurecat, Centre Tecnològic de Catalunya, Technological Unit of Nutrition and Health, 43204 Reus, Spain
4
Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, and Girona Biomedical Research Institute (IDIBGI), 17007 Girona, Spain
5
Center for Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Antioxidants 2020, 9(1), 79; https://doi.org/10.3390/antiox9010079
Received: 3 December 2019 / Revised: 7 January 2020 / Accepted: 14 January 2020 / Published: 16 January 2020
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. View Full-Text
Keywords: metabolic syndrome; cafeteria diet; polyphenols; citrus flavanones; hesperidin; metabolomics; metabolic phenotyping; gut microbiome metabolic syndrome; cafeteria diet; polyphenols; citrus flavanones; hesperidin; metabolomics; metabolic phenotyping; gut microbiome
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Guirro, M.; Gual-Grau, A.; Gibert-Ramos, A.; Alcaide-Hidalgo, J.M.; Canela, N.; Arola, L.; Mayneris-Perxachs, J. Metabolomics Elucidates Dose-Dependent Molecular Beneficial Effects of Hesperidin Supplementation in Rats Fed an Obesogenic Diet. Antioxidants 2020, 9, 79.

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