title: Perinatal lead (Pb) exposure results in sex-specific effects on food intake, fat, weight, and insulin response across the murine life-course.
abstract: Developmental lead (Pb) exposure has been associated with lower body weight in human infants and late onset obesity in mice. We determined the association of perinatal Pb exposure in mice with changes in obesity-related phenotypes into adulthood. Mice underwent exposure via maternal drinking water supplemented with 0 (control), 2.1 (low), 16 (medium), or 32 (high) ppm Pb-acetate two weeks prior to mating through lactation. Offspring were phenotyped at ages 3, 6, and 9 months for energy expenditure, spontaneous activity, food intake, body weight, body composition, and at age 10 months for glucose tolerance. Data analyses were stratified by sex and adjusted for litter effects. Exposed females and males exhibited increased energy expenditure as compared to controls (p<0.0001 for both). In females, horizontal activity differed significantly from controls (p = 0.02) over the life-course. Overall, food intake increased in exposed females and males (p<0.0008 and p<0.0001, respectively) with significant linear trends at 9 months in females (p = 0.01) and 6 months in males (p<0.01). Body weight was significantly increased in males at the medium and high exposures (p = 0.001 and p = 0.006). Total body fat differed among exposed females and males (p<0.0001 and p<0.0001, respectively). Insulin response was significantly increased in medium exposure males (p<0.05). Perinatal Pb exposure at blood lead levels between 4.1 µg/dL and 32 µg/dL is associated with increased food intake, body weight, total body fat, energy expenditure, activity, and insulin response in mice. Physiological effects of developmental Pb exposure persist and vary according to sex and age.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Faulk
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Barks
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.
authors.forename: Brisa N
authors.initials: BN
authors.lastname: Sánchez
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.
authors.forename: Olivia S
authors.initials: OS
authors.lastname: Anderson
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America; Center for Human Growth and Development, University of Michigan, Ann Arbor, Michigan, United States of America; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Peterson
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Dolinoy
mesh_terms: D000367:Age Factors; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005951:Glucose Tolerance Test; D007854:Lead / Q000032:analysis / Q000633:toxicity*; D016014:Linear Models; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008892:Milk / Q000009:adverse effects / Q000737:chemistry*; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D007854:Lead
references.citation: Diabetes. 2013 Aug;62(8):2773-83
references.pmid: 23545705
references.citation: Environ Health Perspect. 2009 Aug;117(8):1195-201
references.pmid: 19672397
references.citation: Arch Intern Med. 2005 Oct 10;165(18):2155-61
references.pmid: 16217007
references.citation: FASEB J. 2013 Apr;27(4):1784-92
references.pmid: 23345456
references.citation: Mutat Res. 2008 Jul-Aug;659(1-2):166-75
references.pmid: 18436472
references.citation: Reprod Toxicol. 2006 Nov;22(4):586-90
references.pmid: 16713174
references.citation: Toxicol Lett. 2013 Feb 13;217(1):75-81
references.pmid: 23246732
references.citation: Arch Environ Health. 2002 Sep-Oct;57(5):482-8
references.pmid: 12641193
references.citation: J Alzheimers Dis. 2011;27(4):819-33
references.pmid: 21891863
references.citation: Environ Health Perspect. 2008 Mar;116(3):355-61
references.pmid: 18335103
references.citation: Environ Health Perspect. 2012 Mar;120(3):445-50
references.pmid: 21947582
references.citation: Environ Health Perspect. 2007 Oct;115(10):1467-73
references.pmid: 17938737
references.citation: Nature. 2012 Jan 11;481(7382):463-8
references.pmid: 22237023
references.citation: Neurotoxicology. 2006 Sep;27(5):693-701
references.pmid: 16889836
references.citation: Pharmacol Biochem Behav. 1998 Jan;59(1):183-9
references.pmid: 9443554
references.citation: J Am Coll Nutr. 2004 Dec;23(6 Suppl):588S-595S
references.pmid: 15640511
references.citation: Sci Total Environ. 2003 Feb 15;303(1-2):79-104
references.pmid: 12568766
references.citation: J Pediatr. 2012 Jun;160(6):1044-9
references.pmid: 22284921
references.citation: Ann Hum Biol. 2009 May-Jun;36(3):331-41
references.pmid: 19381987
references.citation: Environ Health Perspect. 2014 May;122(5):485-91
references.pmid: 24487385
references.citation: Environ Health Perspect. 2011 Oct;119(10):1436-41
references.pmid: 21715242
references.citation: Environ Health Perspect. 2012 Jul;120(7):a268
references.pmid: 22759595
references.citation: Reprod Toxicol. 2004 Nov;19(1):35-41
references.pmid: 15336710
references.citation: Metabolism. 1979 Nov;28(11):1086-96
references.pmid: 386029
references.citation: Mech Ageing Dev. 1998 Apr 1;101(3):245-56
references.pmid: 9622228
references.citation: Mol Cell Biol. 2003 Aug;23(15):5293-300
references.pmid: 12861015
references.citation: Nature. 2004 Jul 22;430(6998):419-21
references.pmid: 15269759
references.citation: J Womens Health (Larchmt). 2010 Sep;19(9):1603-7
references.pmid: 20815755
references.citation: Environ Health Perspect. 2010 Dec;118(12):1782-7
references.pmid: 20675266
references.citation: Interdiscip Toxicol. 2012 Jun;5(2):47-58
references.pmid: 23118587
references.citation: Metab Brain Dis. 2013 Mar;28(1):85-92
references.pmid: 23315312
references.citation: PLoS One. 2009;4(4):e5370
references.pmid: 19401758
references.citation: Pediatrics. 1997 Nov;100(5):856-62
references.pmid: 9346987
references.citation: Biol Trace Elem Res. 2010 Sep;136(3):269-78
references.pmid: 19851721
references.citation: Epigenomics. 2013;5(5):487-500
references.pmid: 24059796
references.citation: Int J Environ Res Public Health. 2010 Sep;7(9):3332-47
references.pmid: 20948927
references.citation: Przegl Lek. 2001;58(4):315-24
references.pmid: 11450360
references.citation: Environ Health Perspect. 2002 Oct;110(10):A599-606
references.pmid: 12361941
references.citation: Environ Health Perspect. 1995 Oct;103(10):952-7
references.pmid: 8529592
references.citation: Nat Genet. 1999 Nov;23(3):314-8
references.pmid: 10545949
references.citation: Acta Neurobiol Exp (Wars). 1997;57(4):275-81
references.pmid: 9519545
references.citation: Environ Health Perspect. 1998 Jan;106(1):1-8
references.pmid: 9417769
references.citation: Toxicol Sci. 2000 Sep;57(1):87-94
references.pmid: 10966514