title: Increased expression of DNA methyltransferase 3a in obese adipose tissue: studies with transgenic mice.
abstract: Epigenetic mechanisms are likely to be involved in the development of obesity. This study was designed to examine the role of a DNA methyltransferase (Dnmt3a), in obese adipose tissue. The gene expression of Dnmts was examined by quantitative real-time PCR analysis. Transgenic mice overexpressing Dnmt3a in the adipose tissue driven by the aP2 promoter were created (Dnmt3a mice). DNA methylation of downregulated genes was examined using bisulfite DNA methylation analysis. Dnmt3a mice were fed a methyl-supplemented or high-fat diet, and subjected to body weight measurement and gene expression analysis of the adipose tissue. Expression of Dnmt3a was markedly upregulated in the adipose tissue of obese mice. The complementary DNA (cDNA) microarray analysis of Dnmt3a mice revealed a slight decrease in the gene expression of secreted frizzled-related protein 1 (SFRP1) and marked increase in that of interferon responsive factor 9 (IRF9). In the SFRP1 promoter, DNA methylation was not markedly increased in Dnmt3a mice relative to wild-type mice. In experiments with a high-fat diet or methyl-supplemented diet, body weight did not differ significantly with the genotypes. Gene expression levels of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) were higher in Dnmt3a mice than in wild-type mice on a high-fat diet. This study suggests that increased expression of Dnmt3a in the adipose tissue may contribute to obesity-related inflammation. The data highlight the potential role of Dnmt3a in the adult tissue as well as in the developing embryo and cancer.
authors.affiliation: Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kamei
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suganami
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ehara
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kanai
authors.forename: Koji
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Miura
authors.forename: Osamu
authors.initials: O
authors.lastname: Ezaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Okano
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005838:Genotype; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D018932:Chemokine CCL2; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D004041:Dietary Fats; D050556:Fatty Acid-Binding Proteins; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C491768:Ccl2 protein, mouse; C000715535:Dnmt3a protein, mouse; C485539:Sfrp1 protein, mouse; D000094742:Secreted Frizzled-Related Proteins