Open AccessPotential miRNA involvement in the anti-adipogenic effect of resveratrol and its metabolites
Author(s) -
Itziar Eseberri,
Arrate Lasa,
Jonatan Miranda,
Ana Gràcia,
Marı́a P. Portillo
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0184875
Subject(s) - microrna , resveratrol , transcription factor , biology , peroxisome proliferator activated receptor , regulation of gene expression , mir 155 , microbiology and biotechnology , chemistry , receptor , biochemistry , gene
Objective Scientific research is constantly striving to find molecules which are effective against excessive body fat and its associated complications. Taking into account the beneficial effects that resveratrol exerts on other pathologies through miRNA, the aim of the present work was to analyze the possible involvement of miRNAs in the regulation of adipogenic transcription factors peroxisome proliferator-activated receptor γ (ppa r γ) , CCAAT enhancer-binding proteins α and β ( cebpβ and cebpα) induced by resveratrol and its metabolites. Methods 3T3-L1 maturing pre-adipocytes were treated during differentiation with 25 μM of trans -resveratrol (RSV), trans -resveratrol-3-O-sulfate (3S), trans -resveratrol-3'-O-glucuronide (3G) and trans -resveratrol-4'-O-glucuronide (4G). After computational prediction and bibliographic search of miRNAs targeting ppa r γ , cebpβ and cebpα , the expression of microRNA-130b-3p (miR-130b-3p), microRNA-155-5p (miR-155-5p), microRNA-27b-3p (miR-27b-3p), microRNA-31-5p (miR-31-5p), microRNA-326-3p (miR-326-3p), microRNA-27a-3p (miR-27a-3p), microRNA-144-3p (miR-144-3p), microRNA-205-5p (miR-205-5p) and microRNA-224-3p (miR-224-3p) was analyzed. Moreover, other adipogenic mediators such as sterol regulatory element binding transcription factor 1 ( srebf1 ), krüppel-like factor 5 ( klf5 ), liver x receptor α ( lxrα ) and cAMP responding element binding protein 1 ( creb1 ), were measured by Real Time RT-PCR. As a confirmatory assay, cells treated with RSV were transfected with anti-miR-155 in order to measure cebpβ gene and protein expressions. Results Of the miRNAs analyzed only miR-155 was modified after resveratrol and glucuronide metabolite treatment. In transfected cells with anti-miR-155, RSV did not reduce cebpβ gene and protein expression. 3S decreased gene expression of creb1 , klf5 , srebf1 and lxrα . Conclusions While RSV and glucuronide metabolites exert their inhibitory effect on adipogenesis through miR-155 up-regulation, the anti-adipogenic effect of 3S is not mediated via miRNAs.