title: Specific CpG hyper-methylation leads to Ankrd26 gene down-regulation in white adipose tissue of a mouse model of diet-induced obesity.
abstract: Epigenetic modifications alter transcriptional activity and contribute to the effects of environment on the individual risk of obesity and Type 2 Diabetes (T2D). Here, we have estimated the in vivo effect of a fat-enriched diet (HFD) on the expression and the epigenetic regulation of the Ankyrin repeat domain 26 (Ankrd26) gene, which is associated with the onset of these disorders. In visceral adipose tissue (VAT), HFD exposure determined a specific hyper-methylation of Ankrd26 promoter at the -436 and -431 bp CpG sites (CpGs) and impaired its expression. Methylation of these 2 CpGs impaired binding of the histone acetyltransferase/transcriptional coactivator p300 to this same region, causing hypo-acetylation of histone H4 at the Ankrd26 promoter and loss of binding of RNA Pol II at the Ankrd26 Transcription Start Site (TSS). In addition, HFD increased binding of DNA methyl-transferases (DNMTs) 3a and 3b and methyl-CpG-binding domain protein 2 (MBD2) to the Ankrd26 promoter. More importantly, Ankrd26 down-regulation enhanced secretion of pro-inflammatory mediators by 3T3-L1 adipocytes as well as in human sera. Thus, in mice, the exposure to HFD induces epigenetic silencing of the Ankrd26 gene, which contributes to the adipose tissue inflammatory secretion profile induced by high-fat regimens.
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Raciti
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Spinelli
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Desiderio
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Longo
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Parrillo
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nigro
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: D'Esposito
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mirra
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fiory
authors.affiliation: Bariatric and Metabolic Surgery Unit, University of Salerno, Salerno, 84084, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pilone
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Forestieri
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Formisano
authors.affiliation: Laboratory of Molecular Biology (LMB), National Cancer Institute (NCI), National Institute of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Miele
authors.affiliation: URT of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, Naples, 80131, Italy.|Department of Translational Medical Sciences, University of Naples "Federico II", Naples, 80131, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Beguinot
mesh_terms: D000107:Acetylation; D017667:Adipocytes / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins / Q000235:genetics*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism; D009765:Obesity / Q000209:etiology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: C526207:Ankrd26 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; C000717967:DNMT3A protein, human; D006657:Histones; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D009707:Nucleosomes; D014157:Transcription Factors; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D050880:p300-CBP Transcription Factors; D012319:RNA Polymerase II