Obesity is associated with depot-specific alterations in adipocyte DNA methylation and gene expression

Si Brask Sonne, Rachita Yadav, Guangliang Yin, Marlene Danner Dalgaard, Lene Secher Myrmel, Ramneek Gupta, Jun Wang, Lise Madsen, Shingo Kajimura, Karsten Kristiansen

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Abstract

The present study aimed to identify genes exhibiting concomitant obesity-dependent changes in DNA methylation and gene expression in adipose tissues in the mouse using diet-induced obese (DIO) C57BL/6J and genetically obese ob/ob mice as models. Mature adipocytes were isolated from epididymal and inguinal adipose tissues of ob/ob and DIO C57BL/6J mice. DNA methylation was analyzed by MeDIP-sequencing and gene expression by microarray analysis. The majority of differentially methylated regions (DMRs) were hypomethylated in obese mice. Global methylation of long interspersed elements indicated that hypomethylation did not reflect methyl donor deficiency. In both DIO and ob/ob mice, we observed more obesity-associated methylation changes in epididymal than in inguinal adipocytes. Assignment of DMRs to promoter, exon, intron and intergenic regions demonstrated that DIO-induced changes in DNA methylation in C57BL/6J mice occurred primarily in exons, whereas inguinal adipocytes of ob/ob mice exhibited a higher enrichment of DMRs in promoter regions than in other regions of the genome, suggesting an influence of leptin on DNA methylation in inguinal adipocytes. We observed altered methylation and expression of 9 genes in epididymal adipocytes, including the known obesity-associated genes, Ehd2 and Kctd15, and a novel candidate gene, Irf8, possibly involved in immune type 1/type2 balance. The use of 2 obesity models enabled us to dissociate changes associated with high fat feeding from those associated with obesity per se. This information will be of value in future studies on the mechanisms governing the development of obesity and changes in adipocyte function associated with obesity.
Original languageEnglish
JournalAdipocyte (Philadelphia)
Volume6
Issue number2
Pages (from-to)124-133
Number of pages10
ISSN2162-3945
DOIs
Publication statusPublished - 2017

Keywords

  • Epididymal adipose tissue
  • Gene expression
  • Global DNA methylation
  • Inguinal adipose tissue
  • Obesity

Cite this

Sonne, Si Brask ; Yadav, Rachita ; Yin, Guangliang ; Dalgaard, Marlene Danner ; Myrmel, Lene Secher ; Gupta, Ramneek ; Wang, Jun ; Madsen, Lise ; Kajimura, Shingo ; Kristiansen, Karsten. / Obesity is associated with depot-specific alterations in adipocyte DNA methylation and gene expression. In: Adipocyte (Philadelphia). 2017 ; Vol. 6, No. 2. pp. 124-133.
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abstract = "The present study aimed to identify genes exhibiting concomitant obesity-dependent changes in DNA methylation and gene expression in adipose tissues in the mouse using diet-induced obese (DIO) C57BL/6J and genetically obese ob/ob mice as models. Mature adipocytes were isolated from epididymal and inguinal adipose tissues of ob/ob and DIO C57BL/6J mice. DNA methylation was analyzed by MeDIP-sequencing and gene expression by microarray analysis. The majority of differentially methylated regions (DMRs) were hypomethylated in obese mice. Global methylation of long interspersed elements indicated that hypomethylation did not reflect methyl donor deficiency. In both DIO and ob/ob mice, we observed more obesity-associated methylation changes in epididymal than in inguinal adipocytes. Assignment of DMRs to promoter, exon, intron and intergenic regions demonstrated that DIO-induced changes in DNA methylation in C57BL/6J mice occurred primarily in exons, whereas inguinal adipocytes of ob/ob mice exhibited a higher enrichment of DMRs in promoter regions than in other regions of the genome, suggesting an influence of leptin on DNA methylation in inguinal adipocytes. We observed altered methylation and expression of 9 genes in epididymal adipocytes, including the known obesity-associated genes, Ehd2 and Kctd15, and a novel candidate gene, Irf8, possibly involved in immune type 1/type2 balance. The use of 2 obesity models enabled us to dissociate changes associated with high fat feeding from those associated with obesity per se. This information will be of value in future studies on the mechanisms governing the development of obesity and changes in adipocyte function associated with obesity.",
keywords = "Epididymal adipose tissue, Gene expression, Global DNA methylation, Inguinal adipose tissue, Obesity",
author = "Sonne, {Si Brask} and Rachita Yadav and Guangliang Yin and Dalgaard, {Marlene Danner} and Myrmel, {Lene Secher} and Ramneek Gupta and Jun Wang and Lise Madsen and Shingo Kajimura and Karsten Kristiansen",
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Sonne, SB, Yadav, R, Yin, G, Dalgaard, MD, Myrmel, LS, Gupta, R, Wang, J, Madsen, L, Kajimura, S & Kristiansen, K 2017, 'Obesity is associated with depot-specific alterations in adipocyte DNA methylation and gene expression', Adipocyte (Philadelphia), vol. 6, no. 2, pp. 124-133. https://doi.org/10.1080/21623945.2017.1320002

Obesity is associated with depot-specific alterations in adipocyte DNA methylation and gene expression. / Sonne, Si Brask; Yadav, Rachita; Yin, Guangliang; Dalgaard, Marlene Danner; Myrmel, Lene Secher; Gupta, Ramneek; Wang, Jun; Madsen, Lise; Kajimura, Shingo; Kristiansen, Karsten.

In: Adipocyte (Philadelphia), Vol. 6, No. 2, 2017, p. 124-133.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Obesity is associated with depot-specific alterations in adipocyte DNA methylation and gene expression

AU - Sonne, Si Brask

AU - Yadav, Rachita

AU - Yin, Guangliang

AU - Dalgaard, Marlene Danner

AU - Myrmel, Lene Secher

AU - Gupta, Ramneek

AU - Wang, Jun

AU - Madsen, Lise

AU - Kajimura, Shingo

AU - Kristiansen, Karsten

PY - 2017

Y1 - 2017

N2 - The present study aimed to identify genes exhibiting concomitant obesity-dependent changes in DNA methylation and gene expression in adipose tissues in the mouse using diet-induced obese (DIO) C57BL/6J and genetically obese ob/ob mice as models. Mature adipocytes were isolated from epididymal and inguinal adipose tissues of ob/ob and DIO C57BL/6J mice. DNA methylation was analyzed by MeDIP-sequencing and gene expression by microarray analysis. The majority of differentially methylated regions (DMRs) were hypomethylated in obese mice. Global methylation of long interspersed elements indicated that hypomethylation did not reflect methyl donor deficiency. In both DIO and ob/ob mice, we observed more obesity-associated methylation changes in epididymal than in inguinal adipocytes. Assignment of DMRs to promoter, exon, intron and intergenic regions demonstrated that DIO-induced changes in DNA methylation in C57BL/6J mice occurred primarily in exons, whereas inguinal adipocytes of ob/ob mice exhibited a higher enrichment of DMRs in promoter regions than in other regions of the genome, suggesting an influence of leptin on DNA methylation in inguinal adipocytes. We observed altered methylation and expression of 9 genes in epididymal adipocytes, including the known obesity-associated genes, Ehd2 and Kctd15, and a novel candidate gene, Irf8, possibly involved in immune type 1/type2 balance. The use of 2 obesity models enabled us to dissociate changes associated with high fat feeding from those associated with obesity per se. This information will be of value in future studies on the mechanisms governing the development of obesity and changes in adipocyte function associated with obesity.

AB - The present study aimed to identify genes exhibiting concomitant obesity-dependent changes in DNA methylation and gene expression in adipose tissues in the mouse using diet-induced obese (DIO) C57BL/6J and genetically obese ob/ob mice as models. Mature adipocytes were isolated from epididymal and inguinal adipose tissues of ob/ob and DIO C57BL/6J mice. DNA methylation was analyzed by MeDIP-sequencing and gene expression by microarray analysis. The majority of differentially methylated regions (DMRs) were hypomethylated in obese mice. Global methylation of long interspersed elements indicated that hypomethylation did not reflect methyl donor deficiency. In both DIO and ob/ob mice, we observed more obesity-associated methylation changes in epididymal than in inguinal adipocytes. Assignment of DMRs to promoter, exon, intron and intergenic regions demonstrated that DIO-induced changes in DNA methylation in C57BL/6J mice occurred primarily in exons, whereas inguinal adipocytes of ob/ob mice exhibited a higher enrichment of DMRs in promoter regions than in other regions of the genome, suggesting an influence of leptin on DNA methylation in inguinal adipocytes. We observed altered methylation and expression of 9 genes in epididymal adipocytes, including the known obesity-associated genes, Ehd2 and Kctd15, and a novel candidate gene, Irf8, possibly involved in immune type 1/type2 balance. The use of 2 obesity models enabled us to dissociate changes associated with high fat feeding from those associated with obesity per se. This information will be of value in future studies on the mechanisms governing the development of obesity and changes in adipocyte function associated with obesity.

KW - Epididymal adipose tissue

KW - Gene expression

KW - Global DNA methylation

KW - Inguinal adipose tissue

KW - Obesity

U2 - 10.1080/21623945.2017.1320002

DO - 10.1080/21623945.2017.1320002

M3 - Journal article

VL - 6

SP - 124

EP - 133

JO - Adipocyte (Philadelphia)

JF - Adipocyte (Philadelphia)

SN - 2162-3945

IS - 2

ER -