title: Long-term supplementation with a low dose of proanthocyanidins normalized liver miR-33a and miR-122 levels in high-fat diet-induced obese rats.
abstract: Deregulation of miR-33 and miR-122, as major regulators of lipid metabolism in liver, has been related to obesity and metabolic syndrome. Proanthocyanidins repress these microRNAs in healthy animals. Hence, we hypothesized that long-term consumption of dietary proanthocyanidins can normalize the expression of miR-33a and miR-122. Therefore, the objective of this work was to determine whether the long-term consumption of proanthocyanidins could effectively normalize the expression of miR-33a and miR-122 in rats made obese by a high-fat diet and to determine the effective dose. Rats were maintained on the high-fat diet with or without supplementation with a grape seed proanthocyanidin extract at low, medium, or high dose in relation to human consumption. Results show that 3 weeks of supplementation with grape seed proanthocyanidin extract normalized the overexpression of miR-33a and miR-122 in obese rats' liver for all doses studied, with no dose-dependent outcome, and also reduced the levels of plasma and liver lipids in a dose-dependent manner. In conclusion, a low sustained dose of proanthocyanidins, lower than the estimated mean intake for a European population, is enough to normalize miR-33a and miR-122 levels in the livers of obese rats. Therefore, a proanthocyanidin-rich diet during obesity can improve some of the metabolic syndrome symptoms at least at the molecular level.
authors.affiliation: Nutrigenomic Research group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, C/Marcel.lí Domingo s/n, 43007 Tarragona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Baselga-Escudero
authors.affiliation: Nutrigenomic Research group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, C/Marcel.lí Domingo s/n, 43007 Tarragona, Spain.
authors.forename: Aïda
authors.initials: A
authors.lastname: Pascual-Serrano
authors.affiliation: Nutrigenomic Research group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, C/Marcel.lí Domingo s/n, 43007 Tarragona, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Ribas-Latre
authors.affiliation: Nutrigenomic Research group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, C/Marcel.lí Domingo s/n, 43007 Tarragona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Casanova
authors.affiliation: Nutrigenomic Research group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, C/Marcel.lí Domingo s/n, 43007 Tarragona, Spain.
authors.forename: M Josepa
authors.initials: MJ
authors.lastname: Salvadó
authors.affiliation: Nutrigenomic Research group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, C/Marcel.lí Domingo s/n, 43007 Tarragona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Arola
authors.affiliation: Nutrigenomic Research group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, C/Marcel.lí Domingo s/n, 43007 Tarragona, Spain. Electronic address: anna.arola@urv.cat.
authors.forename: Anna
authors.initials: A
authors.lastname: Arola-Arnal
authors.affiliation: Nutrigenomic Research group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, C/Marcel.lí Domingo s/n, 43007 Tarragona, Spain.
authors.forename: Cinta
authors.initials: C
authors.lastname: Bladé
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000188:drug therapy / Q000209:etiology; D005260:Female; D056604:Grape Seed Extract / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy*; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
chemical_list: D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; C580643:MIRN122 microRNA, rat; C580642:MIRN33 microRNA, rat; D035683:MicroRNAs; D044945:Proanthocyanidins; D014280:Triglycerides; D002784:Cholesterol
keywords: Abca1; Fas; Flavonoids; MicroRNAs; Obesity; Rat