PMID- 19680236
OWN - NLM
STAT- MEDLINE
DCOM- 20100222
LR  - 20211203
IS  - 1930-739X (Electronic)
IS  - 1930-7381 (Linking)
VI  - 18
IP  - 2
DP  - 2010 Feb
TI  - Increased expression of DNA methyltransferase 3a in obese adipose tissue: studies 
      with transgenic mice.
PG  - 314-21
LID - 10.1038/oby.2009.246 [doi]
AB  - 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.
FAU - Kamei, Yasutomi
AU  - Kamei Y
AD  - Department of Molecular Medicine and Metabolism, Medical Research Institute, 
      Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Suganami, Takayoshi
AU  - Suganami T
FAU - Ehara, Tatsuya
AU  - Ehara T
FAU - Kanai, Sayaka
AU  - Kanai S
FAU - Hayashi, Koji
AU  - Hayashi K
FAU - Yamamoto, Yuji
AU  - Yamamoto Y
FAU - Miura, Shinji
AU  - Miura S
FAU - Ezaki, Osamu
AU  - Ezaki O
FAU - Okano, Masaki
AU  - Okano M
FAU - Ogawa, Yoshihiro
AU  - Ogawa Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090813
PL  - United States
TA  - Obesity (Silver Spring)
JT  - Obesity (Silver Spring, Md.)
JID - 101264860
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Dietary Fats)
RN  - 0 (Dnmt3a protein, mouse)
RN  - 0 (Fatty Acid-Binding Proteins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interferon-Stimulated Gene Factor 3, gamma Subunit)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sfrp1 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
RN  - EC 2.1.1.37 (DNA Methyltransferase 3A)
SB  - IM
MH  - Adipose Tissue/*enzymology/pathology
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - DNA (Cytosine-5-)-Methyltransferases/genetics/*metabolism
MH  - DNA Methylation
MH  - DNA Methyltransferase 3A
MH  - Dietary Fats/adverse effects
MH  - Disease Models, Animal
MH  - Fatty Acid-Binding Proteins/genetics
MH  - Gene Expression Profiling/methods
MH  - Genotype
MH  - Inflammation Mediators/metabolism
MH  - Intercellular Signaling Peptides and Proteins/genetics
MH  - Interferon-Stimulated Gene Factor 3, gamma Subunit/genetics
MH  - Male
MH  - Membrane Proteins/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Obesity/*enzymology/genetics/pathology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phenotype
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/genetics
MH  - Up-Regulation
EDAT- 2009/08/15 09:00
MHDA- 2010/02/23 06:00
CRDT- 2009/08/15 09:00
PHST- 2009/08/15 09:00 [entrez]
PHST- 2009/08/15 09:00 [pubmed]
PHST- 2010/02/23 06:00 [medline]
AID - oby2009246 [pii]
AID - 10.1038/oby.2009.246 [doi]
PST - ppublish
SO  - Obesity (Silver Spring). 2010 Feb;18(2):314-21. doi: 10.1038/oby.2009.246. Epub 
      2009 Aug 13.