title: Epigenetics of programmed obesity: alteration in IUGR rat hepatic IGF1 mRNA expression and histone structure in rapid vs. delayed postnatal catch-up growth.
abstract: Maternal food restriction (FR) during pregnancy results in intrauterine growth-restricted (IUGR) offspring that show rapid catch-up growth and develop metabolic syndrome and adult obesity. However, continued nutrient restriction during nursing delays catch-up growth and prevents development of obesity. Epigenetic regulation of IGF1, which modulates growth and is synthesized and secreted by the liver, may play a role in the development of these morbidities. Control (AdLib) pregnant rats received ad libitum food through gestation and lactation, and FR dams were exposed to 50% food restriction from days 10 to 21. FR pups were nursed by either ad libitum-fed control dams (FR/AdLib) or FR dams (FR/FR). All pups were weaned to ad libitum feed. Maternal FR resulted in IUGR newborns with significantly lower liver weight and, with the use of chromatin immunoprecipitation, decreased dimethylation at H3K4 in the IGF1 region was observed. Obese adult FR/AdLib males had decreased dimethylation and increased trimethylation of H3K4 in the IGF1 region. This corresponded to an increase in mRNA expression of IGF1-A (134 ± 5%), IGF1-B (165 ± 6%), IGF1 exon 1 (149 ± 6%), and IGF1 exon 2 (146 ± 7%) in the FR/AdLib compared with the AdLib/AdLib control group. In contrast, nonobese FR/FR had significantly higher IGF1-B mRNA levels (147 ± 19%) than controls with no difference in IGF1-A, exon 1 or exon 2. Modulation of the rate of IUGR newborn catch-up growth may thus protect against IGF1 epigenetic modifications and, consequently, obesity and associated metabolic abnormalities.
authors.affiliation: David Geffen School of Medicine at University of California Los Angeles, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, California, USA. darran.tosh@unisa.edu.au
authors.forename: Darran N
authors.initials: DN
authors.lastname: Tosh
authors.forename: Qi
authors.initials: Q
authors.lastname: Fu
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Callaway
authors.forename: Robert A
authors.initials: RA
authors.lastname: McKnight
authors.forename: Isabella C
authors.initials: IC
authors.lastname: McMillen
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ross
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lane
authors.forename: Mina
authors.initials: M
authors.lastname: Desai
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000254:growth & development / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014886:Weaning
chemical_list: D006657:Histones; D007334:Insulin-Like Growth Factor I
references.citation: Comp Biochem Physiol B Biochem Mol Biol. 1998 Sep;121(1):3-11
references.pmid: 9972279
references.citation: Nutrition. 2004 Jan;20(1):63-8
references.pmid: 14698016
references.citation: Rev Reprod. 1997 May;2(2):105-12
references.pmid: 9414472
references.citation: J Endocrinol Invest. 2005;28(11 Suppl Proceedings):96-100
references.pmid: 16760634
references.citation: Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R11-5
references.pmid: 15590991
references.citation: Eur J Epidemiol. 2003;18(8):733-6
references.pmid: 12974544
references.citation: Minerva Endocrinol. 2002 Dec;27(4):299-311
references.pmid: 12511852
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7324-9
references.pmid: 10377413
references.citation: Am J Obstet Gynecol. 2005 Sep;193(3 Pt 2):1224-32
references.pmid: 16157142
references.citation: Endocrinology. 1993 Apr;132(4):1797-807
references.pmid: 8462477
references.citation: Eur J Hum Genet. 2007 Jan;15(1):10-7
references.pmid: 17047674
references.citation: Genetics. 2003 Dec;165(4):2055-62
references.pmid: 14704185
references.citation: Nature. 2004 May 27;429(6990):457-63
references.pmid: 15164071
references.citation: Physiol Rev. 2005 Apr;85(2):571-633
references.pmid: 15788706
references.citation: DNA Cell Biol. 1993 Apr;12(3):243-51
references.pmid: 8466647
references.citation: Cell. 1993 Oct 8;75(1):73-82
references.pmid: 8402902
references.citation: Physiol Genomics. 2004 Dec 15;20(1):108-16
references.pmid: 15494474
references.citation: Mol Endocrinol. 2005 Mar;19(3):563-73
references.pmid: 15677708
references.citation: JAMA. 1995 Oct 4;274(13):1049-57
references.pmid: 7563456
references.citation: Hum Mol Genet. 2006 Apr 15;15 Spec No 1:R95-101
references.pmid: 16651376
references.citation: J Nutr. 2004 Sep;134(9):2169-72
references.pmid: 15333699
references.citation: Mol Endocrinol. 1991 Nov;5(11):1677-86
references.pmid: 1779970
references.citation: Mutat Res. 2006 Aug 30;600(1-2):46-57
references.pmid: 16854438
references.citation: Endocrinology. 2002 Jan;143(1):146-54
references.pmid: 11751603
references.citation: Nucleic Acids Res. 2002 Jun 1;30(11):2365-73
references.pmid: 12034823
references.citation: FASEB J. 2009 Aug;23(8):2438-49
references.pmid: 19364764
references.citation: Curr Opin Neurol. 2001 Feb;14(1):95-102
references.pmid: 11176224
references.citation: Cell. 2001 Apr 20;105(2):165-8
references.pmid: 11336665
references.citation: Psychiatry Clin Neurosci. 1999 Aug;53(4):531-3
references.pmid: 10498238
references.citation: Nat Protoc. 2008;3(6):1101-8
references.pmid: 18546601
references.citation: Nature. 2000 Nov 9;408(6809):255-62
references.pmid: 11089983
references.citation: Science. 2001 Apr 6;292(5514):107-10
references.pmid: 11292875
references.citation: Exp Gerontol. 2003 Nov-Dec;38(11-12):1299-307
references.pmid: 14698809
references.citation: Neurobiol Aging. 2006 Mar;27(3):501-5
references.pmid: 16464659
references.citation: Cell. 1993 Oct 8;75(1):59-72
references.pmid: 8402901
references.citation: Diabetologia. 2002 Mar;45(3):342-8
references.pmid: 11914739
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9
references.pmid: 16009939
references.citation: Endocrinology. 1992 Dec;131(6):2793-9
references.pmid: 1446616
references.citation: J Exp Zool. 1998 Sep-Oct 1;282(1-2):239-44
references.pmid: 9723180
references.citation: Nat Rev Genet. 2006 Jan;7(1):21-33
references.pmid: 16369569
references.citation: MedGenMed. 2004 Dec 20;6(4):17
references.pmid: 15775844
references.citation: Nat Genet. 2003 Mar;33 Suppl:245-54
references.pmid: 12610534
references.citation: Horm Res. 2006;65 Suppl 3:28-33
references.pmid: 16612111
references.citation: Science. 2001 Apr 6;292(5514):104-6
references.pmid: 11292874
references.citation: Trends Endocrinol Metab. 2002 Nov;13(9):392-7
references.pmid: 12367821
references.citation: Endocr Rev. 1989 Feb;10(1):68-91
references.pmid: 2666112
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10413-4
references.pmid: 16027353
references.citation: Keio J Med. 2006 Jun;55(2):59-63
references.pmid: 16830417
references.citation: Cell. 2005 Jan 28;120(2):169-81
references.pmid: 15680324
references.citation: Physiol Genomics. 2004 Jun 17;18(1):43-50
references.pmid: 15084713
references.citation: Am J Obstet Gynecol. 2007 Jun;196(6):555.e1-7
references.pmid: 17547893
references.citation: Nature. 2002 Sep 26;419(6905):407-11
references.pmid: 12353038
references.citation: Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R91-6
references.pmid: 15297266
references.citation: Endocrinology. 2001 Dec;142(12):5089-96
references.pmid: 11713201
references.citation: FASEB J. 2006 Oct;20(12):2127-9
references.pmid: 16940436
references.citation: Mol Genet Metab. 2005 Sep-Oct;86(1-2):84-90
references.pmid: 16165387