title: Involvement of miR-539-5p in the inhibition of de novo lipogenesis induced by resveratrol in white adipose tissue.
abstract: The epigenetic mechanisms of action of resveratrol as an anti-obesity molecule have not been fully addressed so far. The aim of the present study was to assess changes produced by resveratrol in the microRNA (miRNA) profile in white adipose tissue (WAT) and to relate these changes to those induced in the expression of genes involved in triacylglycerol metabolism. Male Wistar rats were fed (6 weeks) an obesogenic diet: a control group and a group treated with resveratrol (30 mg kg(-1) d(-1)). A miRNA microarray was carried out in perirenal adipose tissue. The overexpression of miR-539-5p and miR-1224-5p was performed in 3T3-L1 cells. Protein expression was analysed by western-blot and gene expression by qRT-PCR. Associations between variables were assessed by Pearson's correlations. The microarray showed that 3 miRNAs were decreased and 13 were increased after resveratrol treatment. Among those miRNAs increased, miR-129, miR-328-5p and miR-539-5p showed predicted target genes relevant for triacylglycerol metabolism in WAT (pparγ: peroxisome proliferator-activated receptor gamma, hsl: hormone sensitive lipase and sp1: SP1 transcription factor) in the miRWalk database. Moreover, the literature shows that miR-1224, another miRNA up-regulated by resveratrol, can also regulate sp1. Among the three targets, only SP1 showed a reduction in protein expression. Correlation and overexpression studies revealed that the decrease in SP1 protein expression was only associated with the increase of miR-539-5p. In addition, significant reductions in SREBP1 protein expression and fasn gene expression were found in resveratrol-treated rats. In conclusion, the up-regulation of miR-539-5p is involved in the inhibition of de novo lipogenesis induced by resveratrol in WAT.
authors.affiliation: Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lacaray Research Institute, Vitoria, Spain. mariapuy.portillo@ehu.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Gracia
authors.affiliation: Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lacaray Research Institute, Vitoria, Spain. mariapuy.portillo@ehu.es and CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Miranda
authors.affiliation: Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lacaray Research Institute, Vitoria, Spain. mariapuy.portillo@ehu.es and CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fernández-Quintela
authors.affiliation: Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lacaray Research Institute, Vitoria, Spain. mariapuy.portillo@ehu.es and CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Eseberri
authors.affiliation: Department of Nutrition, Food Sciences and Physiology, Centre for Nutrition Research, University of Navarra, Pamplona, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Garcia-Lacarte
authors.affiliation: Department of Nutrition, Food Sciences and Physiology, Centre for Nutrition Research, University of Navarra, Pamplona, Spain and CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain.
authors.forename: Fermín I
authors.initials: FI
authors.lastname: Milagro
authors.affiliation: Department of Nutrition, Food Sciences and Physiology, Centre for Nutrition Research, University of Navarra, Pamplona, Spain and CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain.
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lacaray Research Institute, Vitoria, Spain. mariapuy.portillo@ehu.es and CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain.
authors.forename: Leixuri
authors.initials: L
authors.lastname: Aguirre
authors.affiliation: Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lacaray Research Institute, Vitoria, Spain. mariapuy.portillo@ehu.es and CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Spain.
authors.forename: María P
authors.initials: MP
authors.lastname: Portillo
mesh_terms: D041721:3T3-L1 Cells; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: C000601630:MIRN539 microRNA, mouse; C000612890:MIRN539 microRNA, rat; D035683:MicroRNAs; D047495:PPAR gamma; D013267:Stilbenes; D000077185:Resveratrol