title: Developmental origins of obesity and type 2 diabetes: molecular aspects and role of chemicals.
abstract: Obesity is a leading risk factor for impaired glucose tolerance and type 2 diabetes (T2D). Although the cause of the obesity epidemic is multi-factorial and not entirely clear, the recent acceleration in incidence is too rapid to be accounted for only by genetics, the wide availability of calorie-rich foods, and increasingly sedentary lifestyles. Accumulating data suggest that the important causes of the obesity epidemic may be related to developmental and early life environmental conditions. The concept of the developmental origins of health and disease (DOHaD) suggests that adverse influences early in development, particularly during intrauterine life, may result in permanent changes in the physiology and metabolism of the infant, which in turn result in an increased risk of non-communicable diseases in adulthood. For example, undernutrition during pregnancy and rapid postnatal weight gain are associated with obesity and T2D in the adult offspring. Moreover, increasing evidence suggests that early-life exposure to a wide range of chemicals has a significant impact on the causes of metabolic disorders. Although the underlying molecular mechanisms remain to be determined, these factors can affect epigenetic processes, such as DNA methylation, allowing the developmental environment to modulate gene transcription. The objective of this review article was to summarize recent progress in the biomedical implications of the DOHaD concept, focusing on the pathogenesis of obesity and T2D, and to discuss a future direction for preventive strategies from a public health perspective.
authors: Department of Public Health, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. inadera@med.u-toyama.ac.jp
authors: Hidekuni
authors: H
authors: Inadera
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D009747:Nutritional Physiological Phenomena; D009765:Obesity / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D012307:Risk Factors; D013256:Steroids / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D004785:Environmental Pollutants; D013256:Steroids
references: Chemosphere. 2008 Feb;70(9):1676-84
references: 17764717
references: J Hypertens. 2001 Jan;19(1):29-34
references: 11204301
references: J Nutr. 2005 Jun;135(6):1382-6
references: 15930441
references: Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17046-9
references: 18955703
references: N Engl J Med. 1976 Aug 12;295(7):349-53
references: 934222
references: Diabet Med. 2003 May;20(5):339-48
references: 12752481
references: Environ Int. 2010 Jul;36(5):410-4
references: 20381150
references: Mol Pharmacol. 2005 Mar;67(3):766-74
references: 15611480
references: Physiol Res. 2007;56(4):375-382
references: 16925464
references: Mol Nutr Food Res. 2007 Jul;51(7):912-7
references: 17604389
references: Physiol Rev. 2005 Apr;85(2):571-633
references: 15788706
references: Toxicol Appl Pharmacol. 2011 Aug 15;255(1):65-75
references: 21683088
references: Nature. 2001 Dec 13;414(6865):782-7
references: 11742409
references: Lancet. 1989 Sep 9;2(8663):577-80
references: 2570282
references: Lancet. 2011 Feb 12;377(9765):557-67
references: 21295846
references: Obes Res. 2003 Mar;11(3):461-8
references: 12634446
references: Thorax. 2000 Jul;55(7):555-61
references: 10856314
references: Science. 2001 Aug 10;293(5532):1068-70
references: 11498573
references: Placenta. 2009 May;30(5):411-7
references: 19362366
references: Circulation. 1996 Dec 15;94(12):3246-50
references: 8989136
references: Am J Clin Nutr. 2006 Aug;84(2):322-7; quiz 466-7
references: 16895878
references: J Intern Med. 2007 May;261(5):453-60
references: 17444884
references: Circ Res. 2007 Mar 2;100(4):520-6
references: 17255528
references: J Pediatr. 2000 Apr;136(4):490-6
references: 10753247
references: Diabetologia. 2006 Apr;49(4):637-43
references: 16470406
references: Environ Sci Technol. 2012 Jul 17;46(14):7799-810
references: 22681243
references: Med Anthropol. 2001;20(1):25-64
references: 11820766
references: Epidemiology. 2006 Jul;17(4):352-9
references: 16755267
references: Lancet. 2005 May 28-Jun 3;365(9474):1856-62
references: 15924982
references: Eur J Epidemiol. 2006;21(10):759-65
references: 17082900
references: Am J Epidemiol. 1994 Mar 1;139(5):484-92
references: 8154472
references: Paediatr Perinat Epidemiol. 2003 Oct;17(4):391-7
references: 14629322
references: Annu Rev Physiol. 2011;73:135-62
references: 21054169
references: J Clin Invest. 2008 Jun;118(6):2316-24
references: 18464933
references: Lancet. 1998 Jan 17;351(9097):173-7
references: 9449872
references: Endocrinology. 2012 Mar;153(3):1025-30
references: 22253427
references: Exp Biol Med (Maywood). 2004 Dec;229(11):1127-35
references: 15564439
references: PLoS One. 2010 Oct 22;5(10):e13582
references: 21042579
references: N Engl J Med. 2008 Jul 3;359(1):61-73
references: 18596274
references: BMJ. 1998 Jul 25;317(7153):241-5
references: 9677213
references: Environ Health Perspect. 2008 Jan;116(1):39-44
references: 18197297
references: Nutrition. 2004 Jan;20(1):63-8
references: 14698016
references: Diabetes. 2012 Jun;61(6):1391-8
references: 22461568
references: Environ Res. 2008 Mar;106(3):379-83
references: 18045586
references: Hum Mol Genet. 2009 Nov 1;18(21):4046-53
references: 19656776
references: Acta Paediatr. 2008 Oct;97(10):1465-9
references: 18665907
references: Pediatr Res. 2007 May;61(5 Pt 2):5R-10R
references: 17413851
references: Br J Nutr. 2010 Jun;103(12):1711-9
references: 20211039
references: JAMA. 2004 Dec 8;292(22):2755-64
references: 15585736
references: Reprod Toxicol. 2007 Aug-Sep;24(2):139-77
references: 17825522
references: Diabetologia. 2006 Dec;49(12):2853-8
references: 17096117
references: Obesity (Silver Spring). 2010 Mar;18(3):588-92
references: 19779478
references: Hum Biol. 2000 Aug;72(4):641-54
references: 11048791
references: Int J Epidemiol. 2007 Dec;36(6):1196-204
references: 17591638
references: Environ Health Perspect. 2009 Jan;117(1):122-6
references: 19165398
references: Diabetologia. 1994 Feb;37(2):150-4
references: 8163048
references: Endocrinology. 2011 Aug;152(8):3049-61
references: 21586551
references: Eur J Pediatr. 2002 Aug;161(8):445-8
references: 12172830
references: Lancet. 1986 May 10;1(8489):1077-81
references: 2871345
references: Int J Epidemiol. 2005 Jun;34(3):655-63
references: 15764690
references: Environ Health Perspect. 2007 Oct;115(10):1442-7
references: 17938733
references: Diabetologia. 2007 Sep;50(9):1841-1851
references: 17624515
references: Occup Environ Med. 2009 Mar;66(3):143-9
references: 19060027
references: Lancet. 1996 Nov 9;348(9037):1269-73
references: 8909379
references: Biol Reprod. 2002 Dec;67(6):1734-40
references: 12444047
references: Diabetes Care. 2003 Nov;26(11):3006-10
references: 14578231
references: Mol Endocrinol. 2010 Mar;24(3):526-39
references: 20160124
references: Br J Nutr. 2008 Aug;100(2):278-82
references: 18186951
references: Mol Cell Endocrinol. 2009 May 25;304(1-2):97-105
references: 19433254
references: Endocrinology. 2012 Mar;153(3):1174-82
references: 22210741
references: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19351-6
references: 18042717
references: Lancet. 2002 Aug 31;360(9334):659-65
references: 12241871
references: Environ Health Perspect. 2012 May;120(5):668-73
references: 22306490
references: Pediatr Endocrinol Rev. 2008 Dec;6(2):241-7
references: 19202511
references: Am J Clin Nutr. 2007 Oct;86(4):1219-24
references: 17921405
references: PLoS One. 2008;3(11):e3745
references: 19015723
references: Nat Rev Genet. 2007 Apr;8(4):253-62
references: 17363974
references: Am J Clin Nutr. 1999 Nov;70(5):811-6
references: 10539740
references: Environ Res. 2011 Aug;111(6):825-30
references: 21676388
references: Am J Clin Nutr. 2000 Nov;72(5):1101-6
references: 11063435
references: Am J Physiol Regul Integr Comp Physiol. 2006 Jan;290(1):R1-R10
references: 16352854
references: Environ Health Perspect. 2001 Jul;109(7):675-80
references: 11485865
references: Eur J Endocrinol. 2006 Jul;155(1):153-60
references: 16793962
references: Endocr Rev. 2012 Jun;33(3):378-455
references: 22419778
references: J Biol Chem. 2007 Jun 29;282(26):19152-66
references: 17468099
references: J Atheroscler Thromb. 2007 Oct;14(5):245-52
references: 17938543
references: Environ Health Perspect. 2009 Oct;117(10):1549-55
references: 20019905
references: Sci Total Environ. 2008 Jul 25;399(1-3):90-5
references: 18436279
references: Diabetes. 2011 May;60(5):1528-34
references: 21471513
references: Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13056-61
references: 17670942
references: Am J Physiol Endocrinol Metab. 2000 Jul;279(1):E83-7
references: 10893326
references: Mol Cell Biol. 2003 Aug;23(15):5293-300
references: 12861015
references: Diabetes Care. 2006 May;29(5):1052-7
references: 16644636
references: Hypertension. 2001 Dec 1;38(6):1282-8
references: 11751704
references: Environ Health Perspect. 2010 Sep;118(9):1235-42
references: 20444671
references: J Clin Invest. 1998 May 15;101(10):2174-81
references: 9593773
references: Am J Clin Nutr. 2009 Jun;89(6):1737-43
references: 19386743
references: Heart. 2000 Dec;84(6):595-8
references: 11083734
references: Diabetologia. 1996 Sep;39(9):1119-22
references: 8877298
references: J Hypertens. 2006 Sep;24(9):1771-8
references: 16915026
references: Nature. 1999 Oct 21;401(6755):763-4
references: 10548101
references: Environ Health. 2012 Jun 27;11:42
references: 22715989
references: Eur J Epidemiol. 2005;20(8):673-6
references: 16151880
references: J Prev Med Public Health. 2010 Jan;43(1):1-8
references: 20185977
references: Am J Clin Nutr. 2012 Jan;95(1):179-83
references: 22170371
references: Diabetes Care. 2006 Jul;29(7):1638-44
references: 16801591
references: Am J Hum Biol. 2007 Jan-Feb;19(1):1-19
references: 17160980
references: Am J Physiol Endocrinol Metab. 2007 Nov;293(5):E1451-8
references: 17895287
references: Curr Diab Rep. 2012 Feb;12(1):67-74
references: 22127642
references: Neuroendocrinology. 1996 Dec;64(6):412-8
references: 8990073
references: BMJ. 1993 Feb 13;306(6875):422-6
references: 8461722
references: Biochem Pharmacol. 2002 Mar 1;63(5):997-1007
references: 11911853
references: Diabetes Care. 2008 Aug;31(8):1574-9
references: 18487481
references: Reprod Toxicol. 2005 Sep-Oct;20(3):345-52
references: 15893910
references: Epidemiology. 2000 Jan;11(1):44-8
references: 10615842
references: Lancet. 1996 Nov 30;348(9040):1478-80
references: 8942776
references: Birth Defects Res A Clin Mol Teratol. 2005 Jul;73(7):478-80
references: 15959888
references: Chemosphere. 2009 Aug;76(6):847-52
references: 19409598
references: J Clin Endocrinol Metab. 2011 Dec;96(12):3873-80
references: 21994962
references: Clin Pharmacol Ther. 2012 Dec;92(6):707-15
references: 23047653
references: Br J Pharmacol. 1980 May;69(1):151-7
references: 6247004
references: Annu Rev Nutr. 2010 Aug 21;30:315-39
references: 20415585
references: Nihon Eiseigaku Zasshi. 2011 Jan;66(1):31-8
references: 21358130
references: Br J Nutr. 2007 Mar;97(3):435-9
references: 17313703
references: Mol Cell Endocrinol. 2009 May 25;304(1-2):84-9
references: 19433252
references: Int J Food Sci Nutr. 2000 Jan;51(1):11-7
references: 10746100
references: N Engl J Med. 2004 Nov 18;351(21):2179-86
references: 15548778
references: Environ Health Perspect. 2007 Dec;115(12):1747-52
references: 18087594
references: Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R34-8
references: 15178540
references: Endocr Rev. 2009 Jun;30(4):293-342
references: 19502515
references: PLoS One. 2009 Oct 19;4(10):e7503
references: 19838294
references: Epidemiology. 1997 May;8(3):252-8
references: 9115019
references: Diabetologia. 1993 Jan;36(1):62-7
references: 8436255
references: Toxicol Lett. 2005 Dec 15;159(3):226-34
references: 15993011
references: Am J Clin Nutr. 2007 Mar;85(3):869-76
references: 17344511
references: Toxicol Sci. 2003 Dec;76(2):247-9
references: 14677558
references: J Occup Environ Med. 2008 Mar;50(3):330-40
references: 18332783
references: Public Health Nutr. 2001 Apr;4(2B):611-24
references: 11683554
references: Br J Haematol. 2000 Oct;111(1):112-7
references: 11091189
references: Atherosclerosis. 2007 Aug;193(2):421-7
references: 16914156
references: J Hypertens. 1997 May;15(5):537-44
references: 9170007
references: Mol Endocrinol. 2006 Sep;20(9):2141-55
references: 16613991
references: Science. 2004 Sep 17;305(5691):1733-6
references: 15375258
references: Environ Health Perspect. 2011 Feb;119(2):272-8
references: 20923745
references: Lancet. 2006 Aug 12;368(9535):558-9
references: 16905002
references: Epidemiology. 2009 Nov;20(6):921-8
references: 19797969
references: Diabetologia. 2010 May;53(5):899-906
references: 20182860
references: Birth Defects Res C Embryo Today. 2011 Mar;93(1):34-50
references: 21425440
references: Development. 2000 Oct;127(19):4195-202
references: 10976051
references: Diabetes. 2009 Dec;58(12):2718-25
references: 19940235
references: J Hypertens. 1999 Mar;17(3):325-30
references: 10100069
references: Diabetes Care. 2006 Aug;29(8):1897-901
references: 16873799
references: Am J Epidemiol. 2006 Aug 15;164(4):317-25
references: 16775040
references: Arch Gen Psychiatry. 1996 Jan;53(1):25-31
references: 8540774
references: Br J Nutr. 2008 Mar;99(3):540-9
references: 17761015
references: Environ Health Perspect. 2011 Jun;119(6):878-85
references: 21233055
references: Environ Health Perspect. 2009 Jul;117(7):1076-82
references: 19654916
references: Lancet. 1993 Feb 6;341(8841):339-41
references: 8094115
references: Science. 2005 Jun 3;308(5727):1466-9
references: 15933200
references: Biol Neonate. 1990;57(2):107-18
references: 2178691
references: Diabetologia. 1992 Jul;35(7):595-601
references: 1644236
references: Clin Nutr. 1994 Oct;13(5):319-24
references: 16843406
references: Genes Dev. 2002 Jan 1;16(1):6-21
references: 11782440
references: Lancet. 1993 Apr 10;341(8850):938-41
references: 8096277
references: Diabetes. 2003 May;52(5):1210-4
references: 12716754
references: J Altern Complement Med. 2002 Apr;8(2):185-92
references: 12006126
references: Mol Cell Endocrinol. 2009 May 25;304(1-2):90-6
references: 19433253
references: Int J Epidemiol. 2002 Apr;31(2):413-9
references: 11980805
references: Endocrinology. 2012 Sep;153(9):4216-26
references: 22807491