title: Early postnatal nutrition determines adult physical activity and energy expenditure in female mice.
abstract: Decades of research in rodent models has shown that early postnatal overnutrition induces excess adiposity and other components of metabolic syndrome that persist into adulthood. The specific biologic mechanisms explaining the persistence of these effects, however, remain unknown. On postnatal day 1 (P1), mice were fostered in control (C) or small litters (SL). SL mice had increased body weight and adiposity at weaning (P21), which persisted to adulthood (P180). Detailed metabolic studies indicated that female adult SL mice have decreased physical activity and energy expenditure but not increased food intake. Genome-scale DNA methylation profiling identified extensive changes in hypothalamic DNA methylation during the suckling period, suggesting that it is a critical period for developmental epigenetics in the mouse hypothalamus. Indeed, SL mice exhibited subtle and sex-specific changes in hypothalamic DNA methylation that persisted from early life to adulthood, providing a potential mechanistic basis for the sustained physiological effects. Expression profiling in adult hypothalamus likewise provided evidence of widespread sex-specific alterations in gene expression. Together, our data indicate that early postnatal overnutrition leads to a reduction in spontaneous physical activity and energy expenditure in females and suggest that early postnatal life is a critical period during which nutrition can affect hypothalamic developmental epigenetics.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: John J
authors.initials: JJ
authors.lastname: Kohorst
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhang
authors.forename: Eleonora
authors.initials: E
authors.lastname: Laritsky
authors.forename: Govindarajan
authors.initials: G
authors.lastname: Kunde-Ramamoorthy
authors.forename: Maria S
authors.initials: MS
authors.lastname: Baker
authors.forename: Marta L
authors.initials: ML
authors.lastname: Fiorotto
authors.forename: Robert A
authors.initials: RA
authors.lastname: Waterland
mesh_terms: D050154:Adiposity / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D019175:DNA Methylation; D004435:Eating / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology*; D009752:Nutritional Status; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D044343:Overnutrition / Q000235:genetics / Q000378:metabolism
references.citation: Biotechniques. 2007 Jan;42(1):48, 50, 52 passim
references.pmid: 17269485
references.citation: Am J Physiol. 1998 Oct;275(4):R1374-9
references.pmid: 9756571
references.citation: Physiol Behav. 2005 Dec 15;86(5):646-60
references.pmid: 16289141
references.citation: Am J Clin Nutr. 1999 Feb;69(2):179-97
references.pmid: 9989679
references.citation: J Hepatol. 2010 Jun;52(6):913-20
references.pmid: 20413174
references.citation: Science. 2004 Apr 2;304(5667):108-10
references.pmid: 15064420
references.citation: Am J Clin Nutr. 2009 Jun;89(6):1836-45
references.pmid: 19386747
references.citation: Endocrinology. 2010 Oct;151(10):4756-64
references.pmid: 20685869
references.citation: J Physiol. 2009 Oct 15;587(Pt 20):4963-76
references.pmid: 19723777
references.citation: Eur J Neurosci. 2010 Dec;32(12):2096-104
references.pmid: 21143664
references.citation: Nat Rev Endocrinol. 2010 Oct;6(10):543-9
references.pmid: 20736922
references.citation: Nat Rev Genet. 2009 May;10(5):295-304
references.pmid: 19308066
references.citation: Br J Nutr. 2002 Sep;88(3):301-6
references.pmid: 12207840
references.citation: Science. 2008 May 30;320(5880):1224-9
references.pmid: 18511691
references.citation: Crit Rev Food Sci Nutr. 2009 Nov;49(10):868-913
references.pmid: 19960394
references.citation: Int J Obes (Lond). 2007 Jul;31(7):1035-43
references.pmid: 17589539
references.citation: Endocrinology. 2007 Sep;148(9):4150-9
references.pmid: 17525123
references.citation: J Nutr. 1982 Jul;112(7):1339-43
references.pmid: 6808095
references.citation: Diabetes. 2011 Jan;60(1):17-23
references.pmid: 21193735
references.citation: Hum Mol Genet. 2010 Jun 1;19(11):2168-76
references.pmid: 20197410
references.citation: Genome Res. 2011 May;21(5):688-96
references.pmid: 21467265
references.citation: Endocrinology. 2011 May;152(5):2100-12
references.pmid: 21343250
references.citation: BMC Bioinformatics. 2009 Feb 03;10:48
references.pmid: 19192299
references.citation: Mol Cell. 2010 Feb 26;37(4):457-68
references.pmid: 20188665
references.citation: Curr Opin Neurobiol. 2009 Apr;19(2):207-12
references.pmid: 19545993
references.citation: Diabetes. 2012 Nov;61(11):2833-41
references.pmid: 22751689
references.citation: PLoS Genet. 2010 Dec 23;6(12):e1001252
references.pmid: 21203497
references.citation: Science. 2004 Apr 2;304(5667):110-5
references.pmid: 15064421
references.citation: Endocrinology. 2010 Feb;151(2):702-13
references.pmid: 20016030
references.citation: Mol Cell Biol. 2003 Aug;23(15):5293-300
references.pmid: 12861015
references.citation: Neuroscience. 2004;129(4):983-91
references.pmid: 15561413
references.citation: J Infect Dis. 2011 Apr 1;203(7):921-9
references.pmid: 21357945
references.citation: Nat Genet. 2003 Mar;33 Suppl:245-54
references.pmid: 12610534
references.citation: Nat Neurosci. 2004 Aug;7(8):847-54
references.pmid: 15220929
references.citation: J Exp Biol. 2011 Jan 15;214(Pt 2):206-29
references.pmid: 21177942
references.citation: Am J Physiol Regul Integr Comp Physiol. 2003 Jul;285(1):R271-3
references.pmid: 12794001
references.citation: Science. 2009 Feb 20;323(5917):1074-7
references.pmid: 19119186
references.citation: J Nutr. 2002 Mar;132(3):357-64
references.pmid: 11880555
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16480-5
references.pmid: 17923673
references.citation: J Clin Invest. 2012 Jan;122(1):142-52
references.pmid: 22201680
references.citation: Metabolism. 2005 Oct;54(10):1316-22
references.pmid: 16154430
references.citation: Neural Dev. 2010 Aug 24;5:21
references.pmid: 20735826
references.citation: Am J Physiol. 1991 Jun;260(6 Pt 2):R1104-13
references.pmid: 2058738
references.citation: J Endocrinol. 1957 Nov;16(1):9-17
references.pmid: 13491729
references.citation: Diabetes. 2009 May;58(5):1116-25
references.pmid: 19188431
references.citation: Nat Neurosci. 2010 Jun;13(6):767-75
references.pmid: 20436479
references.citation: Cell. 2004 Jan 23;116(2):337-50
references.pmid: 14744442
references.citation: J Perinat Med. 2010 Jul;38(4):393-400
references.pmid: 20443665
references.citation: J Endocrinol. 2008 Sep;198(3):591-8
references.pmid: 18599621
references.citation: Brain Res. 1999 Jul 31;836(1-2):146-55
references.pmid: 10415413
references.citation: Annu Rev Nutr. 2007;27:363-88
references.pmid: 17465856
references.citation: PLoS Genet. 2007 Oct;3(10):2023-36
references.pmid: 17967063
references.citation: Bioinformatics. 2008 Jul 1;24(13):1547-8
references.pmid: 18467348
references.citation: J Nutr. 1980 Apr;110(4):649-61
references.pmid: 7365536
references.citation: Hum Mol Genet. 2009 Aug 15;18(16):3026-38
references.pmid: 19457928
references.citation: Nat Rev Endocrinol. 2009 Jul;5(7):401-8
references.pmid: 19488075
references.citation: J Nutr Biochem. 2011 Feb;22(2):109-17
references.pmid: 20303731