title: Plant-derived polyphenols regulate expression of miRNA paralogs miR-103/107 and miR-122 and prevent diet-induced fatty liver disease in hyperlipidemic mice.
abstract: BACKGROUND
  MicroRNAs have the potential for clinical application. Probable modulation by plant-derived polyphenols might open preventive measures using simple dietary recommendations.
  
  
  METHODS
  We assessed the ability of continuous administration of high-dose polyphenols to modulate hepatic metabolism and microRNA expression in diet-induced fatty liver disease in commercially available hyperlipidemic mice using well-established and accepted procedures that included the development of new antibodies against modified quercetin.
  
  
  RESULTS
  Weight gain, liver steatosis, changes in the composition of liver tissue, and insulin resistance were all attenuated by the continuous administration of polyphenols. We also demonstrated that metabolites of polyphenols accumulate in immune cells and at the surface of hepatic lipid droplets indicating not only bioavailability but a direct likely action on liver cells. The addition of polyphenols also resulted in changes in the expression of miR-103, miR-107 and miR-122.
  
  
  CONCLUSIONS
  Polyphenols prevent fatty liver disease under these conditions. The differential expression of mRNAs and miRNAs was also associated with changes in lipid and glucose metabolism and with the activation of 5'-adenosine monophosphate-activated protein kinase, effects that are not necessarily connected. miRNAs function via different mechanisms and miRNA-mRNA interactions are difficult to ascertain with current knowledge. Further, cell models usually elicit contradictory results with those obtained in animal models.
  
  
  CONCLUSIONS
  Our data indicate that plant-derived polyphenols should be tested in humans as preventive rather than therapeutic agents in the regulation of hepatic fatty acid utilization. A multi-faceted mechanism of action is likely and the regulation of liver miRNA expression blaze new trails in further research.
authors.affiliation: Unitat de Recerca Biomèdica (URB-CRB), Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain. jorge.joven@urv.cat
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
authors.forename: Eugenia
authors.initials: E
authors.lastname: Espinel
authors.forename: Anna
authors.initials: A
authors.lastname: Rull
authors.forename: Gerard
authors.initials: G
authors.lastname: Aragonès
authors.forename: Esther
authors.initials: E
authors.lastname: Rodríguez-Gallego
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
authors.forename: Vicente
authors.initials: V
authors.lastname: Micol
authors.forename: María
authors.initials: M
authors.lastname: Herranz-López
authors.forename: Javier A
authors.initials: JA
authors.lastname: Menéndez
authors.forename: Isabel
authors.initials: I
authors.lastname: Borrás
authors.forename: Antonio
authors.initials: A
authors.lastname: Segura-Carretero
authors.forename: Carlos
authors.initials: C
authors.lastname: Alonso-Villaverde
authors.forename: Raúl
authors.initials: R
authors.lastname: Beltrán-Debón
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control*; D031584:Hibiscus / Q000737:chemistry*; D006801:Humans; D006949:Hyperlipidemias / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D059808:Polyphenols / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015430:Weight Gain
chemical_list: C555364:MIRN103 microRNA, mouse; C555365:MIRN107 microRNA, mouse; D035683:MicroRNAs; C544354:Mirn122 microRNA, mouse; D059808:Polyphenols; D012333:RNA, Messenger; D055372:AMP-Activated Protein Kinases