title: Grape seed proanthocyanidins repress the hepatic lipid regulators miR-33 and miR-122 in rats.
abstract: METHODS
  One major health problem in westernized countries is dysregulated fatty acid and cholesterol metabolism that causes pathologies such as metabolic syndrome. Previous studies from our group have shown that proanthocyanidins, which are the most abundant polyphenols in the human diet, regulate lipid metabolism and are potent hypolipidemic agents. The noncoding RNAs, miR-33 and miR-122, regulate genes that are involved in lipid metabolism.
  
  
  RESULTS
  Here, we show that grape seed proanthocyanidins rapidly and transiently repressed the expression of miR-33 and miR-122 in rat hepatocytes in vivo and in vitro. Furthermore, the miR-33 target gene ATP-binding cassette A1 and the miR-122 target gene fatty acid synthase were also modulated by proanthocyanidins. Specifically, ATP-binding cassette A1 mRNA and protein levels were increased, and fatty acid synthase mRNA and protein levels were reduced after the miRNA levels were altered.
  
  
  CONCLUSIONS
  These results suggest that proanthocyanidin treatment increased hepatic cholesterol efflux to produce new HDL particles by repressing miR-33, and it reduced lipogenesis by repressing miR-122. These results highlight a new mechanism by which grape seed proanthocyanidins produce hypolipidemia through their effects on miRNA modulators of lipid metabolism.
authors.affiliation: Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Baselga-Escudero
authors.forename: Cinta
authors.initials: C
authors.lastname: Bladé
authors.forename: Aleix
authors.initials: A
authors.lastname: Ribas-Latre
authors.forename: Ester
authors.initials: E
authors.lastname: Casanova
authors.forename: M Josepa
authors.initials: MJ
authors.lastname: Salvadó
authors.forename: Lluis
authors.initials: L
authors.lastname: Arola
authors.forename: Anna
authors.initials: A
authors.lastname: Arola-Arnal
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D044948:Flavonols / Q000097:blood / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D056604:Grape Seed Extract / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008297:Male; D035683:MicroRNAs / Q000187:drug effects* / Q000235:genetics; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C491898:Fas protein, rat; D044948:Flavonols; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; C580643:MIRN122 microRNA, rat; C580642:MIRN33 microRNA, rat; D035683:MicroRNAs; D044945:Proanthocyanidins; D014280:Triglycerides; D019014:fas Receptor; D002784:Cholesterol