title: An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss.
abstract: BACKGROUND
  Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans.
  
  
  RESULTS
  Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is observed in the 3' untranslated region and gene bodies relative to promoter regions. Differential methylation is found within genes associated with obesity, epigenetic regulation and development, such as CETP, FOXP2, HDAC4, DNMT3B, KCNQ1 and HOX clusters. We identify robust correlations between changes in methylation and clinical trait, including associations between fasting glucose and HDAC4, SLC37A3 and DENND1C in subcutaneous adipose. Genes investigated with differential promoter methylation all show significantly different levels of mRNA before and after gastric bypass.
  
  
  CONCLUSIONS
  This is the first study reporting global DNA methylation profiling of adipose tissue before and after gastric bypass and associated weight loss. It provides a strong basis for future work and offers additional evidence for the role of DNA methylation of adipose tissue in obesity.
authors: Miles C
authors: MC
authors: Benton
authors: Alice
authors: A
authors: Johnstone
authors: David
authors: D
authors: Eccles
authors: Brennan
authors: B
authors: Harmon
authors: Mark T
authors: MT
authors: Hayes
authors: Rod A
authors: RA
authors: Lea
authors: Lyn
authors: L
authors: Griffiths
authors: Eric P
authors: EP
authors: Hoffman
authors: Richard S
authors: RS
authors: Stubbs
authors: Donia
authors: D
authors: Macartney-Coxson
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D004777:Environment; D044127:Epigenesis, Genetic; D005260:Female; D015390:Gastric Bypass; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059647:Gene-Environment Interaction; D005801:Genes, Homeobox; D055106:Genome-Wide Association Study; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D011401:Promoter Regions, Genetic; D019655:Quantitative Trait, Heritable; D012333:RNA, Messenger / Q000235:genetics; D015203:Reproducibility of Results; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012333:RNA, Messenger; C531408:mirn199 microRNA, human
references: Am J Clin Nutr. 2012 Jul;96(1):196-207
references: 22648723
references: Biochem Biophys Res Commun. 2012 Apr 13;420(3):588-93
references: 22445754
references: Int J Epidemiol. 2007 Dec;36(6):1196-204
references: 17591638
references: Lancet. 2005 Nov 5;366(9497):1640-9
references: 16271645
references: Biochem Biophys Res Commun. 2012 Mar 23;419(4):782-9
references: 22390934
references: J Clin Endocrinol Metab. 2011 Feb;96(2):E413-8
references: 21047925
references: Nucleic Acids Res. 2013 Jul;41(Web Server issue):W77-83
references: 23703215
references: FASEB J. 2013 Jun;27(6):2504-12
references: 23475851
references: Am J Physiol Endocrinol Metab. 2013 Apr 1;304(7):E770-9
references: 23423172
references: BMC Med. 2010;8:88
references: 21176136
references: Epigenetics. 2013 May;8(5):522-33
references: 23644594
references: PLoS One. 2013;8(9):e75342
references: 24086512
references: Am J Physiol Endocrinol Metab. 2013 Jun 15;304(12):E1291-302
references: 23571711
references: Diabetologia. 2005 Jan;48(1):123-31
references: 15624093
references: Cell Rep. 2013 Apr 25;3(4):1020-7
references: 23583180
references: Physiol Behav. 2009 Mar 23;96(4-5):723-8
references: 19385027
references: Diabetes. 2012 Jun;61(6):1404-14
references: 22403301
references: PLoS One. 2009;4(10):e7419
references: 19823685
references: PLoS One. 2011;6(4):e17944
references: 21533135
references: Hum Mol Genet. 2009 Nov 1;18(21):4046-53
references: 19656776
references: Am J Clin Nutr. 2010 Feb;91(2):309-20
references: 19939982
references: Trends Pharmacol Sci. 2009 Aug;30(8):387-96
references: 19595466
references: JAMA. 2012 Sep 19;308(11):1122-31
references: 22990271
references: J Clin Endocrinol Metab. 2008 Dec;93(12):4933-40
references: 18812483
references: Obes Rev. 2009 May;10(3):265-8
references: 19175509
references: J Biol Chem. 2010 Apr 2;285(14):10627-37
references: 20154091
references: Cell Signal. 2006 Mar;18(3):382-90
references: 15961276
references: Cell Biol Int. 2013 Nov;37(11):1145-8
references: 23765685
references: Circulation. 2006 Feb 14;113(6):898-918
references: 16380542
references: FASEB J. 2004 Nov;18(14):1657-69
references: 15522911
references: J Clin Endocrinol Metab. 2008 Nov;93(11):4315-22
references: 18782868
references: Am J Clin Nutr. 2010 Oct;92(4):975-84
references: 20739421
references: Diabetes. 2014 Feb;63(2):801-7
references: 24170695
references: J Clin Endocrinol Metab. 2008 Nov;93(11 Suppl 1):S57-63
references: 18987271
references: Arch Surg. 2011 Jun;146(6):744-50
references: 21690453
references: Diabetes. 2011 Jul;60(7):1849-55
references: 21709280
references: Mol Med. 2011;17(11-12):1157-67
references: 21738950
references: Diabetes. 2006 Jun;55(6):1537-45
references: 16731815
references: Epigenetics. 2011 Jun;6(6):692-702
references: 21593595
references: Cell. 2013 Mar 28;153(1):56-69
references: 23540690
references: Diabetes. 2011 May;60(5):1528-34
references: 21471513
references: Nature. 2002 Dec 19-26;420(6917):821-4
references: 12490950
references: Curr Opin Lipidol. 2010 Feb;21(1):38-43
references: 19915462
references: PLoS One. 2012;7(10):e46705
references: 23071618
references: Genome Biol. 2014;15(2):R31
references: 24495553
references: Clin Genet. 2004 Oct;66(4):299-310
references: 15355432
references: Am J Hum Genet. 2013 Nov 7;93(5):876-90
references: 24183450
references: Genes Dev. 2002 Jan 1;16(1):6-21
references: 11782440
references: Horm Metab Res. 2002 Nov-Dec;34(11-12):616-21
references: 12660870
references: Genome Biol. 2004;5(10):R80
references: 15461798
references: Endocr Rev. 2000 Dec;21(6):697-738
references: 11133069
references: Obesity (Silver Spring). 2011 Feb;19(2):388-95
references: 20847730
references: Am J Hum Genet. 2010 Nov 12;87(5):661-6
references: 20950786
references: Bioinformatics. 2014 May 15;30(10):1363-9
references: 24478339
references: Cell. 2014 Jan 16;156(1-2):20-44
references: 24439368
references: Sci Transl Med. 2010 Sep 15;2(49):49ra67
references: 20844285
references: PLoS One. 2013;8(7):e68740
references: 23869231
references: PLoS One. 2012;7(12):e51302
references: 23251491
references: PLoS Med. 2004 Oct;1(1):e27
references: 15526049
references: PLoS One. 2011;6(9):e23944
references: 21915269
references: Eur Heart J. 2008 Dec;29(24):2959-71
references: 18775919
references: Traffic. 2012 Oct;13(10):1429-41
references: 22762500
references: BMC Bioinformatics. 2012;13:86
references: 22568884
references: Mol Biol Cell. 2012 Jan;23(1):163-75
references: 22072793
references: Am J Clin Nutr. 2008 Mar;87(3):744-52
references: 18326614
references: BMC Bioinformatics. 2013;14:359
references: 24330312
references: Lancet. 2014 Jun 7;383(9933):1990-8
references: 24630777
references: J Biol Chem. 2002 Nov 22;277(47):45420-7
references: 12213831
references: BMC Cell Biol. 2007;8:18
references: 17535427
references: Adipocyte. 2013 Jan 1;2(1):3-6
references: 23700546
references: Int J Obes (Lond). 2010 Jun;34(6):949-59
references: 20065965
references: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002 Oct;24(5):474-80
references: 12905768
references: Diabetes. 1999 Apr;48(4):685-90
references: 10102682
references: Cell. 2014 Jan 16;156(1-2):45-68
references: 24439369
references: Diabetologia. 2014 Nov;57(11):2374-83
references: 25145546
references: Bioinformatics. 2014 May 15;30(10):1431-9
references: 24451622
references: Health Aff (Millwood). 2002 Mar-Apr;21(2):245-53
references: 11900166
references: Cell Metab. 2008 Nov;8(5):384-98
references: 19046570
references: Genomics. 2012 Mar;99(3):132-7
references: 22234326
references: Diabetologia. 2011 Aug;54(8):2047-55
references: 21647700
references: Circulation. 2007 Dec 18;116(25):2933-43
references: 18071080
references: Cell Metab. 2006 Mar;3(3):153-65
references: 16517403
references: Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5417-22
references: 22427358
references: Nat Methods. 2012 Apr;9(4):357-9
references: 22388286
references: J Physiol Biochem. 2011 Sep;67(3):463-70
references: 21465273
references: Crit Rev Clin Lab Sci. 2003 Jun;40(3):209-94
references: 12892317
references: PLoS Genet. 2013 Jun;9(6):e1003572
references: 23825961
references: PLoS One. 2012;7(3):e31821
references: 22431966
references: Proc Nutr Soc. 2011 Feb;70(1):57-63
references: 21144123
references: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002 Jun;24(3):223-7
references: 12905622
references: Lancet. 2005 Oct 1;366(9492):1197-209
references: 16198769
references: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W741-8
references: 15980575
references: Sci Signal. 2009;2(72):re3
references: 19471024
references: Drug News Perspect. 2010 Sep;23(7):409-17
references: 20862392
references: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002 Oct;24(5):471-3
references: 12905767
references: N Engl J Med. 2010 Dec 9;363(24):2339-50
references: 21142536
references: J Biol Chem. 2005 Dec 23;280(51):42300-6
references: 16239226
references: Am J Hum Genet. 2012 Jan 13;90(1):7-24
references: 22243964
references: Hum Mol Genet. 2012 Jan 15;21(2):371-83
references: 21994764
references: Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17046-9
references: 18955703
references: J Clin Invest. 2006 Dec;116(12):3240-51
references: 17143332
references: Epigenetics Chromatin. 2013 Aug 06;6(1):26
references: 23919675
references: Am J Med. 2009 Mar;122(3):248-256.e5
references: 19272486
references: Mol Biol Cell. 2012 Oct;23(20):4065-78
references: 22918957
references: PLoS One. 2013;8(3):e58048
references: 23554873
references: Bioinformatics. 2014 Feb 1;30(3):428-30
references: 24336642
references: Int J Obes (Lond). 2008 Feb;32(2):292-303
references: 17848939
references: FASEB J. 2011 Apr;25(4):1378-89
references: 21209057
references: Cell Metab. 2013 Aug 6;18(2):296-302
references: 23931760
references: Obes Surg. 2005 Feb;15(2):155-63
references: 15802056
references: Nat Rev Genet. 2007 Apr;8(4):253-62
references: 17363974
references: Mol Cell Biol. 2004 Jun;24(12):5447-58
references: 15169906
references: Diabetologia. 2005 Feb;48(2):301-8
references: 15660262
references: J Cell Biol. 2010 Oct 18;191(2):367-81
references: 20937701
references: Life Sci. 2004 Nov 19;76(1):57-70
references: 15501480
references: BMC Med. 2010;8:87
references: 21176133