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PMID: 19072643 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Epigenetics and obesity.

Pharmacogenomics ·Vol. 9 ·No. 12 ·2008-12-00 ·Pages 1851-60

Stöger R

Abstract

Common DNA sequence variants inadequately explain variability in fat mass among individuals. Abnormal body weights are characteristic of specific imprinted-gene disorders. However, the relevance of imprinted genes to our understanding of obesity among the general population is uncertain. Hitherto unidentified imprinted genes and epigenetic mosaicism are two of the challenges for this emerging field of epigenetics. Subtle epigenetic differences in imprinted genes and gene networks are likely to be present among cells, tissues and individuals. In order to advance obesity research it will be necessary to use genome-wide, next-generation sequencing approaches that allow the detection of such epigenetic differences.

MeSH Terms
Animals Energy Metabolism/genetics Epigenesis, Genetic Genomic Imprinting Humans Obesity/genetics
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Stöger Reinhard
Department of Biology, University of Washington, 156 Kincaid Hall, Box 351800, Seattle, WA, 98195-1800, USA. stoeger@u.washington.edu
References (119)
119 references, click to expand
  1. Changes in gene expression foreshadow diet-induced obesity in genetically identical mice.
    PLoS Genet. 2006 May;2(5):e81 PMID: 16733553
  2. Assessment of genetic linkage and parent-of-origin effects on obesity.
    J Clin Endocrinol Metab. 2006 Oct;91(10):4001-5 PMID: 16835282
  3. Type 2 (non-insulin-dependent) diabetes--an epidemiological overview.
    Diabetologia. 1982 Jun;22(6):399-411 PMID: 7049798
  4. Waddington's canalization revisited: developmental stability and evolution.
    Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10528-32 PMID: 12082173
  5. Transient neonatal diabetes, a disorder of imprinting.
    J Med Genet. 2002 Dec;39(12):872-5 PMID: 12471198
  6. Assisted reproductive technology in Europe, 2003. Results generated from European registers by ESHRE.
    Hum Reprod. 2007 Jun;22(6):1513-25 PMID: 17470881
  7. Imprints of disease at GNAS1.
    J Clin Invest. 2001 Apr;107(7):793-4 PMID: 11285295
  8. Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus.
    Hum Mol Genet. 2006 Mar 1;15(5):705-16 PMID: 16421170
  9. Chromatin modifications and their function.
    Cell. 2007 Feb 23;128(4):693-705 PMID: 17320507
  10. Relaxation of imprinted genes in human cancer.
    Nature. 1993 Apr 22;362(6422):747-9 PMID: 8385745
  11. In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene.
    Am J Hum Genet. 2003 May;72(5):1338-41 PMID: 12772698
  12. The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes?
    Bioessays. 2008 Feb;30(2):156-66 PMID: 18197594
  13. A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus.
    Hum Genet. 2006 Sep;120(2):262-9 PMID: 16816970
  14. Genomic imprinting in mammals: emerging themes and established theories.
    PLoS Genet. 2006 Nov 24;2(11):e147 PMID: 17121465
  15. Loss of IGF2 imprinting: mechanisms and consequences.
    Novartis Found Symp. 2004;262:108-21; discussion 121-4, 265-8 PMID: 15562825
  16. Epigenetic regulation of metabolism in children born small for gestational age.
    Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):482-8 PMID: 16778581
  17. Genome-wide linkage analysis assessing parent-of-origin effects in the inheritance of birth weight.
    Hum Genet. 2002 May;110(5):503-9 PMID: 12073022
  18. Genome-wide linkage analysis assessing parent-of-origin effects in the inheritance of type 2 diabetes and BMI in Pima Indians.
    Diabetes. 2001 Dec;50(12):2850-7 PMID: 11723070
  19. Imprinted genes, postnatal adaptations and enduring effects on energy homeostasis.
    Adv Exp Med Biol. 2008;626:41-61 PMID: 18372790
  20. Neomorphic agouti mutations in obese yellow mice.
    Nat Genet. 1994 Sep;8(1):59-65 PMID: 7987393
  21. Selective loss of imprinting in the placenta following preimplantation development in culture.
    Development. 2004 Aug;131(15):3727-35 PMID: 15240554
  22. Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians.
    Nat Genet. 2008 Aug;40(8):971-6 PMID: 18587395
  23. Encoding PCR products with batch-stamps and barcodes.
    Biochem Genet. 2007 Dec;45(11-12):761-7 PMID: 17955361
  24. Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour.
    Nature. 1993 Apr 22;362(6422):749-51 PMID: 8097018
  25. Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19.
    Am J Hum Genet. 2003 Jan;72(1):156-60 PMID: 12439823
  26. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.
    Science. 2007 Jun 1;316(5829):1341-5 PMID: 17463248
  27. Genetic linkage and imprinting effects on body mass index in children and young adults.
    Eur J Hum Genet. 2003 Jun;11(6):425-32 PMID: 12774034
  28. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6 PMID: 8790415
  29. The molecular basis for dominant yellow agouti coat color mutations.
    Bioessays. 1994 Oct;16(10):705-7 PMID: 7980472
  30. A census of mammalian imprinting.
    Trends Genet. 2005 Aug;21(8):457-65 PMID: 15990197
  31. Minireview: pharmacogenetics and beyond: the interaction of therapeutic response, beta-cell physiology, and genetics in diabetes.
    Endocrinology. 2006 Jun;147(6):2657-63 PMID: 16556760
  32. Germ-line epigenetic modification of the murine A vy allele by nutritional supplementation.
    Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17308-12 PMID: 17101998
  33. Maternal nutrition and fetal development.
    J Nutr. 2004 Sep;134(9):2169-72 PMID: 15333699
  34. What will whole genome searches for susceptibility genes for common complex disease offer to clinical practice?
    J Intern Med. 2008 Jan;263(1):16-27 PMID: 18088250
  35. Variations in DNA elucidate molecular networks that cause disease.
    Nature. 2008 Mar 27;452(7186):429-35 PMID: 18344982
  36. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells.
    Nature. 2007 Aug 2;448(7153):553-60 PMID: 17603471
  37. Genomic imprinting in mammalian development: a parental tug-of-war.
    Trends Genet. 1991 Feb;7(2):45-9 PMID: 2035190
  38. Satiety dysfunction in Prader-Willi syndrome demonstrated by fMRI.
    J Neurol Neurosurg Psychiatry. 2005 Feb;76(2):260-2 PMID: 15654046
  39. RIP140 directs histone and DNA methylation to silence Ucp1 expression in white adipocytes.
    EMBO J. 2007 Nov 28;26(23):4831-40 PMID: 17972916
  40. ChIP-seq: welcome to the new frontier.
    Nat Methods. 2007 Aug;4(8):613-4 PMID: 17664943
  41. Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development.
    Hum Mol Genet. 2008 Jan 1;17(1):1-14 PMID: 17901045
  42. Mutations of the Gs alpha-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8287-90 PMID: 2122458
  43. Pharmacogenetics: potential role in the treatment of diabetes and obesity.
    Expert Opin Pharmacother. 2008 May;9(7):1109-19 PMID: 18422469
  44. Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib.
    Nat Genet. 2005 Jan;37(1):25-7 PMID: 15592469
  45. Neonatal programming of body weight regulation and energetic metabolism.
    Biosci Rep. 2005 Jun-Aug;25(3-4):251-69 PMID: 16283556
  46. Computational and experimental identification of novel human imprinted genes.
    Genome Res. 2007 Dec;17(12):1723-30 PMID: 18055845
  47. Resourceful imprinting.
    Nature. 2004 Nov 4;432(7013):53-7 PMID: 15525980
  48. Culture of preimplantation mouse embryos affects fetal development and the expression of imprinted genes.
    Biol Reprod. 2001 Mar;64(3):918-26 PMID: 11207209
  49. Epigenetic variation illustrated by DNA methylation patterns of the fragile-X gene FMR1.
    Hum Mol Genet. 1997 Oct;6(11):1791-801 PMID: 9302255
  50. Environmental effects on genomic imprinting in mammals.
    Toxicol Lett. 2001 Mar 31;120(1-3):143-50 PMID: 11323171
  51. Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo.
    Biol Reprod. 2000 Jun;62(6):1526-35 PMID: 10819752
  52. Mesoderm-specific transcript is associated with fat mass expansion in response to a positive energy balance.
    FASEB J. 2008 Nov;22(11):3925-37 PMID: 18644838
  53. Physiological functions of the imprinted Gnas locus and its protein variants Galpha(s) and XLalpha(s) in human and mouse.
    J Endocrinol. 2008 Feb;196(2):193-214 PMID: 18252944
  54. Genome organization, function, and imprinting in Prader-Willi and Angelman syndromes.
    Annu Rev Genomics Hum Genet. 2001;2:153-75 PMID: 11701647
  55. Parental imprinting and human disease.
    Annu Rev Genet. 1996;30:173-95 PMID: 8982453
  56. Genomic imprinting, growth control and the allocation of nutritional resources: consequences for postnatal life.
    Curr Opin Endocrinol Diabetes Obes. 2007 Feb;14(1):3-12 PMID: 17940412
  57. Beckwith-Wiedemann syndrome and IVF: a case-control study.
    Am J Hum Genet. 2004 Sep;75(3):526-8 PMID: 15284956
  58. Epigenetic deregulation of imprinting in congenital diseases of aberrant growth.
    Bioessays. 2006 May;28(5):453-9 PMID: 16615080
  59. Environmental epigenomics and disease susceptibility.
    Nat Rev Genet. 2007 Apr;8(4):253-62 PMID: 17363974
  60. Variation in epigenetic inheritance.
    Trends Genet. 1990 Apr;6(4):110-4 PMID: 2132729
  61. Epigenetic regulation of transcription: a mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life?
    Br J Nutr. 2007 Jun;97(6):1036-46 PMID: 17381976
  62. Beckwith-Wiedemann syndrome and assisted reproduction technology (ART).
    J Med Genet. 2003 Jan;40(1):62-4 PMID: 12525545
  63. Pharmacogenetics of metformin response: a step in the path toward personalized medicine.
    J Clin Invest. 2007 May;117(5):1226-9 PMID: 17476355
  64. Epigenetic differences arise during the lifetime of monozygotic twins.
    Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9 PMID: 16009939
  65. Developmental origins of adult metabolic disease: concepts and controversies.
    Trends Endocrinol Metab. 2005 Oct;16(8):390-4 PMID: 16118054
  66. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
    Science. 2007 Jun 1;316(5829):1331-6 PMID: 17463246
  67. Epigenetic deregulation of genomic imprinting in human disorders and following assisted reproduction.
    Birth Defects Res C Embryo Today. 2005 Jun;75(2):81-97 PMID: 16035043
  68. A maternal epimutation of GNAS leads to Albright osteodystrophy and parathyroid hormone resistance.
    J Clin Endocrinol Metab. 2008 Mar;93(3):661-5 PMID: 18182455
  69. Genome regulation by polycomb and trithorax proteins.
    Cell. 2007 Feb 23;128(4):735-45 PMID: 17320510
  70. Metastable epialleles in mammals.
    Trends Genet. 2002 Jul;18(7):348-51 PMID: 12127774
  71. Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57.
    Nat Genet. 2008 Aug;40(8):949-51 PMID: 18622393
  72. Variable and tissue-specific hormone resistance in heterotrimeric Gs protein alpha-subunit (Gsalpha) knockout mice is due to tissue-specific imprinting of the gsalpha gene.
    Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8715-20 PMID: 9671744
  73. Molecular barcodes detect redundancy and contamination in hairpin-bisulfite PCR.
    Nucleic Acids Res. 2004 Sep 30;32(17):e135 PMID: 15459281
  74. In vivo methylation patterns of the leptin promoter in human and mouse.
    Epigenetics. 2006 Oct-Dec;1(4):155-62 PMID: 17965621
  75. The imprinted signaling protein XL alpha s is required for postnatal adaptation to feeding.
    Nat Genet. 2004 Aug;36(8):818-26 PMID: 15273686
  76. Peg1/Mest in obese adipose tissue is expressed from the paternal allele in an isoform-specific manner.
    FEBS Lett. 2007 Jan 9;581(1):91-6 PMID: 17182038
  77. Characterization of the extra-large G protein alpha-subunit XLalphas. II. Signal transduction properties.
    J Biol Chem. 2000 Oct 27;275(43):33633-40 PMID: 10931851
  78. Tissue-specific imprinting of the G protein Gsalpha is associated with tissue-specific differences in histone methylation.
    Hum Mol Genet. 2004 Apr 15;13(8):819-28 PMID: 14976161
  79. Transposable elements: targets for early nutritional effects on epigenetic gene regulation.
    Mol Cell Biol. 2003 Aug;23(15):5293-300 PMID: 12861015
  80. Limited evolutionary conservation of imprinting in the human placenta.
    Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6623-8 PMID: 16614068
  81. Epigenomics and sequencing: an intertwined and emerging big science of the next decade.
    Pharmacogenomics. 2007 Sep;8(9):1109-13 PMID: 17924826
  82. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals.
    Nat Genet. 2003 Mar;33 Suppl:245-54 PMID: 12610534
  83. The large-scale organization of metabolic networks.
    Nature. 2000 Oct 5;407(6804):651-4 PMID: 11034217
  84. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.
    Environ Health Perspect. 2006 Apr;114(4):567-72 PMID: 16581547
  85. The mammalian epigenome.
    Cell. 2007 Feb 23;128(4):669-81 PMID: 17320505
  86. Nutritional epigenomics of metabolic syndrome: new perspective against the epidemic.
    Diabetes. 2005 Jul;54(7):1899-906 PMID: 15983188
  87. Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations.
    Br J Nutr. 2007 Mar;97(3):435-9 PMID: 17313703
  88. A mouse model of albright hereditary osteodystrophy generated by targeted disruption of exon 1 of the Gnas gene.
    Endocrinology. 2005 Nov;146(11):4697-709 PMID: 16099856
  89. Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice.
    FASEB J. 1998 Aug;12(11):949-57 PMID: 9707167
  90. Genomic imprinting: parental influence on the genome.
    Nat Rev Genet. 2001 Jan;2(1):21-32 PMID: 11253064
  91. The emerging epidemic of obesity in developing countries.
    Int J Epidemiol. 2006 Feb;35(1):93-9 PMID: 16326822
  92. Possible genomic imprinting of three human obesity-related genetic loci.
    Am J Hum Genet. 2005 Mar;76(3):427-37 PMID: 15647995
  93. In-utero overgrowth in ruminants following embryo culture: lessons from mice and a warning to men.
    Hum Reprod. 2000 Dec;15 Suppl 5:68-86 PMID: 11263539
  94. Next-generation sequencing transforms today's biology.
    Nat Methods. 2008 Jan;5(1):16-8 PMID: 18165802
  95. Maternal effects as the cause of parent-of-origin effects that mimic genomic imprinting.
    Genetics. 2008 Mar;178(3):1755-62 PMID: 18245362
  96. Imprinting in Prader-Willi and Angelman syndromes.
    Trends Genet. 1998 May;14(5):194-200 PMID: 9613204
  97. Noncoding RNAs and gene silencing.
    Cell. 2007 Feb 23;128(4):763-76 PMID: 17320512
  98. Perceptions of epigenetics.
    Nature. 2007 May 24;447(7143):396-8 PMID: 17522671
  99. Phenotypic plasticity and the epigenetics of human disease.
    Nature. 2007 May 24;447(7143):433-40 PMID: 17522677
  100. Severe obesity and insulin resistance due to deletion of the maternal Gsalpha allele is reversed by paternal deletion of the Gsalpha imprint control region.
    Endocrinology. 2008 May;149(5):2443-50 PMID: 18202131
  101. Genomic imprinting effects on adult body composition in mice.
    Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4253-8 PMID: 18337500
  102. Short stature, obesity, and growth hormone deficiency in pseudohypoparathyroidism type 1a.
    Pediatr Endocrinol Rev. 2006 Apr;3 Suppl 2:318-27 PMID: 16675931
  103. Mechanisms of imprinting of the Prader-Willi/Angelman region.
    Am J Med Genet A. 2008 Aug 15;146A(16):2041-52 PMID: 18627066
  104. Mest/Peg1 imprinted gene enlarges adipocytes and is a marker of adipocyte size.
    Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E117-24 PMID: 15353408
  105. Is personalized medicine finally arriving?
    Nat Biotechnol. 2008 May;26(5):509-17 PMID: 18464779
  106. Gametic imprinting in mammals.
    Science. 1995 Dec 8;270(5242):1610-3 PMID: 7502071
  107. Beyond the sequence: cellular organization of genome function.
    Cell. 2007 Feb 23;128(4):787-800 PMID: 17320514
  108. Altered imprinted gene methylation and expression in completely ES cell-derived mouse fetuses: association with aberrant phenotypes.
    Development. 1998 Jun;125(12):2273-82 PMID: 9584126
  109. Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring.
    J Nutr. 2002 Aug;132(8 Suppl):2393S-2400S PMID: 12163699
  110. Large offspring syndrome in cattle and sheep.
    Rev Reprod. 1998 Sep;3(3):155-63 PMID: 9829550
  111. A methyl-deficient diet modifies histone methylation and alters Igf2 and H19 repression in the prostate.
    Prostate. 2008 Aug 1;68(11):1187-95 PMID: 18459101
  112. Epigenetic inheritance at the agouti locus in the mouse.
    Nat Genet. 1999 Nov;23(3):314-8 PMID: 10545949
  113. DNA methylation patterns and epigenetic memory.
    Genes Dev. 2002 Jan 1;16(1):6-21 PMID: 11782440
  114. Does nutrition during infancy and early childhood contribute to later obesity via metabolic imprinting of epigenetic gene regulatory mechanisms?
    Nestle Nutr Workshop Ser Pediatr Program. 2005;56:157-71; discussion 171-4 PMID: 16632951
  115. Alternative Gnas gene products have opposite effects on glucose and lipid metabolism.
    Proc Natl Acad Sci U S A. 2005 May 17;102(20):7386-91 PMID: 15883378
  116. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.
    Science. 2007 Jun 1;316(5829):1336-41 PMID: 17463249
  117. Time to take epigenetic inheritance seriously.
    Eur J Hum Genet. 2002 Nov;10(11):669-71 PMID: 12404095
  118. Diabetes and obesity: the twin epidemics.
    Nat Med. 2006 Jan;12(1):75-80 PMID: 16397575
  119. Genome-wide prediction of imprinted murine genes.
    Genome Res. 2005 Jun;15(6):875-84 PMID: 15930497
Article Info
Journal
Pharmacogenomics
Abbr.
Pharmacogenomics
ISSN
1744-8042
DOI
10.2217/14622416.9.12.1851
Email
stoeger@u.washington.edu
Published
2008-12-00
Pages
1851-60
Language
English
Region
England
NLM ID
100897350
PMCID
PMC2652025
Subset
IM
Grants
NIGMS NIH HHS · R01 GM077464 · United States
NIGMS NIH HHS · R01 GM077464-03 · United States
NIGMS NIH HHS · GM077464 · United States
External Links
PubMed source DOI: 10.2217/14622416.9.12.1851 PMC Full Text View journal details
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