Epigenetics, Obesity and Early-Life Cadmium or Lead Exposure

References

• Ogden CL , CarrollMD , KitBK , FlegalKM . Prevalence of childhood and adult obesity in the United States, 2011–2012 . JAMA311 ( 8 ), 806 – 814 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Cawley J , MeyerhoeferC . The medical care costs of obesity: an instrumental variables approach . J. Health Econ.31 ( 1 ), 219 – 230 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Selassie M , SinhaAC . The epidemiology and aetiology of obesity: a global challenge . Best Pract. Res. Clin. Anaesthesiol.25 ( 1 ), 1 – 9 ( 2011 ).
   PubMedGoogle Scholar
• Atsdr . Agency for toxic substances and disease registry . Secondary Agency for Toxic Substances and Disease Registry ( 2015 ). http://www.atsdr.cdc.gov/ .
   Google Scholar
• Cecil KM , BrubakerCJ , AdlerCMet al. Decreased brain volume in adults with childhood lead exposure . PLoS Med.5 ( 5 ), e112 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Davis JM , SvendsgaardDJ . Lead and child development . Nature329 ( 6137 ), 297 – 300 ( 1987 ).
   PubMed Web of Science ®Google Scholar
• Dietrich KN , KrafftKM , BornscheinRLet al. Low-level fetal lead exposure effect on neurobehavioral development in early infancy . Pediatrics80 ( 5 ), 721 – 730 ( 1987 ).
   PubMed Web of Science ®Google Scholar
• Wang Y , ChenL , GaoYet al. Effects of prenatal exposure to cadmium on neurodevelopment of infants in Shandong, China . Environ. Pollut.211 , 67 – 73 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Berkowitz Z , Price-GreenP , BoveFJ , KayeWE . Lead exposure and birth outcomes in five communities in Shoshone County, Idaho . Int. J. Hyg. Environ. Health209 ( 2 ), 123 – 132 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Gonzalez-Cossio T , PetersonKE , SaninLHet al. Decrease in birth weight in relation to maternal bone-lead burden . Pediatrics100 ( 5 ), 856 – 862 ( 1997 ).
   PubMed Web of Science ®Google Scholar
• Tian LL , ZhaoYC , WangXCet al. Effects of gestational cadmium exposure on pregnancy outcome and development in the offspring at age 4.5 years . Biol. Trace Elem. Res.132 ( 1–3 ), 51 – 59 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Vidal AC , SemenovaV , DarrahTet al. Maternal cadmium, iron and zinc levels, DNA methylation and birth weight . BMC Pharmacol. Toxicol.16 , 20 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Barker DJ , ErikssonJG , ForsenT , OsmondC . Fetal origins of adult disease: strength of effects and biological basis . Int. J. Epidemiol.31 ( 6 ), 1235 – 1239 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Barker DJ , OsmondC , KajantieE , ErikssonJG . Growth and chronic disease: findings in the Helsinki Birth Cohort . Ann. Hum. Biol.36 ( 5 ), 445 – 458 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Eriksson JG , OsmondC , KajantieE , ForsenTJ , BarkerDJ . Patterns of growth among children who later develop Type 2 diabetes or its risk factors . Diabetologia49 ( 12 ), 2853 – 2858 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Karelis AD , St-PierreDH , ConusF , Rabasa-LhoretR , PoehlmanET . Metabolic and body composition factors in subgroups of obesity: what do we know?J. Clin. Endocrinol. Metab.89 ( 6 ), 2569 – 2575 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Muller MJ , LagerpuschM , EnderleJ , SchautzB , HellerM , Bosy-WestphalA . Beyond the body mass index: tracking body composition in the pathogenesis of obesity and the metabolic syndrome . Obes. Rev.13 ( Suppl. 2 ), 6 – 13 ( 2012 ).
   PubMedGoogle Scholar
• Heijmans BT , TobiEW , LumeyLH , SlagboomPE . The epigenome: archive of the prenatal environment . Epigenetics4 ( 8 ), 526 – 531 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Hoyo C , MurphySK , JirtleRL . Imprint regulatory elements as epigenetic biosensors of exposure in epidemiological studies . J. Epidemiol. Community Health63 ( 9 ), 683 – 684 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Ray PD , YosimA , FryRC . Incorporating epigenetic data into the risk assessment process for the toxic metals arsenic, cadmium, chromium, lead and mercury: strategies and challenges . Front. Genet.5 , 201 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Drummond EM , GibneyER . Epigenetic regulation in obesity . Curr. Opin. Clin. Nutr. Metab. Care16 ( 4 ), 392 – 397 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Rhee KE , PhelanS , MccafferyJ . Early determinants of obesity: genetic, epigenetic and in utero influences . Int. J. Pediatr. 2012 , 463850 ( 2012 ).
   PubMedGoogle Scholar
• Sullivan EL , GroveKL . Metabolic imprinting in obesity . Forum Nutr.63 , 186 – 194 ( 2010 ).
   PubMedGoogle Scholar
• Van Dijk SJ , MolloyPL , VarinliH , MorrisonJL , MuhlhauslerBS . Epigenetics and human obesity . Int. J. Obes. (Lond.)39 ( 1 ), 85 – 97 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Feinberg AP . An epigenetic approach to cancer etiology . Cancer J.13 ( 1 ), 70 – 74 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Weidman JR , DolinoyDC , MurphySK , JirtleRL . Cancer susceptibility: epigenetic manifestation of environmental exposures . Cancer J.13 ( 1 ), 9 – 16 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Dalgaard K , LandgrafK , HeyneSet al. Trim28 haploinsufficiency triggers bi-stable epigenetic obesity . Cell164 ( 3 ), 353 – 364 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Mansego ML , Garcia-LacarteM , MilagroFI , MartiA , MartinezJA . DNA methylation of miRNA coding sequences putatively associated with childhood obesity . Pediatr. Obes. doi:10.1111/ijpo.12101 ( 2016 ) ( Epub ahead of print ).
   PubMed Web of Science ®Google Scholar
• Wang S , SongJ , YangY , ZhangY , WangH , MaJ . HIF3A DNA methylation is associated with childhood obesity and ALT . PLoS ONE10 ( 12 ), e0145944 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Huang RC , GarrattES , PanHet al. Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood . Epigenetics10 ( 11 ), 995 – 1005 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Cao-Lei L , DancauseKN , ElgbeiliGet al. DNA methylation mediates the impact of exposure to prenatal maternal stress on BMI and central adiposity in children at age 13(1/2) years: Project Ice Storm . Epigenetics10 ( 8 ), 749 – 761 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Pan H , LinX , WuYet al. HIF3A association with adiposity: the story begins before birth . Epigenomics7 ( 6 ), 937 – 950 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Wu L , ZhaoX , ShenYet al. Influence of lifestyle on the FAIM2 promoter methylation between obese and lean children: a cohort study . BMJ Open5 ( 4 ), e007670 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Eriksson A , WilliamsMJ , VoisinSet al. Implication of coronin 7 in body weight regulation in humans, mice and flies . BMC Neurosci.16 , 13 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Ding X , ZhengD , FanCet al. Genome-wide screen of DNA methylation identifies novel markers in childhood obesity . Gene566 ( 1 ), 74 – 83 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Gardner KR , SapienzaC , FisherJO . Genetic and epigenetic associations to obesity-related appetite phenotypes among African–American children . Pediatr. Obes.10 ( 6 ), 476 – 482 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Wu L , ZhaoX , ShenYet al. Promoter methylation of fas apoptotic inhibitory molecule 2 gene is associated with obesity and dyslipidaemia in Chinese children . Diab. Vasc. Dis. Res.12 ( 3 ), 217 – 220 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Yan Z , ZhangH , MaherCet al. Prenatal polycyclic aromatic hydrocarbon, adiposity, peroxisome proliferator-activated receptor (PPAR) gamma methylation in offspring, grand-offspring mice . PLoS ONE9 ( 10 ), e110706 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Garcia-Cardona MC , HuangF , Garcia-VivasJMet al. DNA methylation of leptin and adiponectin promoters in children is reduced by the combined presence of obesity and insulin resistance . Int. J. Obes. (Lond.)38 ( 11 ), 1457 – 1465 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Azzi S , SasTC , KoudouYet al. Degree of methylation of ZAC1 (PLAGL1) is associated with prenatal and post-natal growth in healthy infants of the EDEN mother child cohort . Epigenetics9 ( 3 ), 338 – 345 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Yoo JY , LeeS , LeeHAet al. Can proopiomelanocortin methylation be used as an early predictor of metabolic syndrome? Diabetes Care 37 ( 3 ), 734 – 739 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Deodati A , InzaghiE , LiguoriAet al. IGF2 methylation is associated with lipid profile in obese children . Horm. Res. Paediatr.79 ( 6 ), 361 – 367 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Xu X , SuS , BarnesVAet al. A genome-wide methylation study on obesity: differential variability and differential methylation . Epigenetics8 ( 5 ), 522 – 533 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Perng W , Mora-PlazasM , MarinC , RozekLS , BaylinA , VillamorE . A prospective study of LINE–1DNA methylation and development of adiposity in school-age children . PLoS ONE8 ( 4 ), e62587 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• St-Pierre J , HivertMF , PerronPet al. IGF2 DNA methylation is a modulator of newborn’s fetal growth and development . Epigenetics7 ( 10 ), 1125 – 1132 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Kuehnen P , MischkeM , WiegandSet al. An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity . PLoS Genet.8 ( 3 ), e1002543 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Relton CL , GroomA , St PourcainBet al. DNA methylation patterns in cord blood DNA and body size in childhood . PLoS ONE7 ( 3 ), e31821 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Almen MS , JacobssonJA , MoschonisGet al. Genome wide analysis reveals association of a FTO gene variant with epigenetic changes . Genomics99 ( 3 ), 132 – 137 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Michels KB , HarrisHR , BaraultL . Birthweight, maternal weight trajectories and global DNA methylation of LINE-1 repetitive elements . PLoS ONE6 ( 9 ), e25254 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Godfrey KM , SheppardA , GluckmanPDet al. Epigenetic gene promoter methylation at birth is associated with child’s later adiposity . Diabetes60 ( 5 ), 1528 – 1534 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Perkins E , MurphySK , MurthaAPet al. Insulin-like growth factor 2/H19 methylation at birth and risk of overweight and obesity in children . J. Pediatr.161 ( 1 ), 31 – 39 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Soubry A , MurphySK , WangFet al. Newborns of obese parents have altered DNA methylation patterns at imprinted genes . Int. J. Obes. (Lond.)39 ( 4 ), 650 – 657 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Hernandez-Valero MA , RotherJ , GorlovI , FrazierM , GorlovaO . Interplay between polymorphisms and methylation in the H19/IGF2 gene region may contribute to obesity in Mexican–American children . J. Dev. Orig. Health Dis.4 ( 6 ), 499 – 506 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Huang RC , GalatiJC , BurrowsSet al. DNA methylation of the IGF2/H19 imprinting control region and adiposity distribution in young adults . Clin. Epigenetics4 ( 1 ), 21 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Leow SC , PoschmannJ , TooPGet al. The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis . Development143 ( 6 ), 950 – 961 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Liu ZW , ZhangJT , CaiQYet al. Birth weight is associated with placental fat mass- and obesity-associated gene expression and promoter methylation in a Chinese population . J. Matern. Fetal Neonatal Med.29 ( 1 ), 106 – 111 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Dave V , YousefiP , HuenK , VolbergV , HollandN . Relationship between expression and methylation of obesity-related genes in children . Mutagenesis30 ( 3 ), 411 – 420 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Lovkvist C , DoddIB , SneppenK , HaerterJO . DNA methylation in human epigenomes depends on local topology of CpG sites . Nucleic Acids Res.44 ( 11 ), 5123 – 5132 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Rastogi D , SuzukiM , GreallyJM . Differential epigenome-wide DNA methylation patterns in childhood obesity-associated asthma . Sci. Rep.3 , 2164 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Sanin LH , Gonzalez-CossioT , RomieuIet al. Effect of maternal lead burden on infant weight and weight gain at one month of age among breastfed infants . Pediatrics107 ( 5 ), 1016 – 1023 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Cassidy-Bushrow AE , HavstadS , BasuNet al. Detectable blood lead level and body size in early childhood . Biol. Trace Elem. Res.171 ( 1 ), 41 – 47 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Delvaux I , Van CauwenbergheJ , Den HondEet al. Prenatal exposure to environmental contaminants and body composition at age 7–9 years . Environ. Res.132 , 24 – 32 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Scinicariello F , BuserMC , MevissenM , PortierCJ . Blood lead level association with lower body weight in NHANES 1999–2006 . Toxicol. Appl. Pharmacol.273 ( 3 ), 516 – 523 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Kim R , HuH , RotnitzkyA , BellingerD , NeedlemanH . A longitudinal study of chronic lead exposure and physical growth in Boston children . Environ. Health Perspect.103 ( 10 ), 952 – 957 ( 1995 ).
   PubMed Web of Science ®Google Scholar
• Wang N , ChenC , NieXet al. Blood lead level and its association with body mass index and obesity in China – results from SPECT-China study . Sci. Rep.5 , 18299 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Rhee SY , HwangYC , WooJTet al. Blood lead is significantly associated with metabolic syndrome in Korean adults: an analysis based on the Korea National Health and Nutrition Examination Survey (KNHANES), 2008 . Cardiovasc. Diabetol.12 , 9 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Lee BK , KimY . Blood cadmium, mercury and lead and metabolic syndrome in South Korea: 2005–2010 Korean National Health and Nutrition Examination Survey . Am. J. Ind. Med.56 ( 6 ), 682 – 692 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Faulk C , BarksA , SanchezBNet al. Perinatal lead (Pb) exposure results in sex-specific effects on food intake, fat, weight and insulin response across the murine life-course . PLoS ONE9 ( 8 ), e104273 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Leasure JL , GiddabasappaA , ChaneySet al. Low-level human equivalent gestational lead exposure produces sex-specific motor and coordination abnormalities and late-onset obesity in year-old mice . Environ. Health Perspect.116 ( 3 ), 355 – 361 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Wu J , WenXW , FaulkCet al. Perinatal lead (Pb) exposure alters gut microbiota composition and results in sex-specific bodyweight increases in adult mice . Toxicol. Sci.151 ( 2 ), 324 – 333 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Faulk C , BarksA , LiuK , GoodrichJM , DolinoyDC . Early-life lead exposure results in dose- and sex-specific effects on weight and epigenetic gene regulation in weanling mice . Epigenomics5 ( 5 ), 487 – 500 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Ba Q , LiM , ChenPet al. Gender-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice . Environ. Health Perspect. doi:10.1289/ehp360 ( 2016 ) ( Epub ahead of print ).
   PubMed Web of Science ®Google Scholar
• Kawakami T , SugimotoH , FuruichiRet al. Cadmium reduces adipocyte size and expression levels of adiponectin and Peg1/Mest in adipose tissue . Toxicology267 ( 1–3 ), 20 – 26 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Nye MD , KingKE , DarrahTHet al. Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort . Environmental Epigenetics doi:10.1093/eep/dvv009 ( 2016 ) ( Epub ahead of print ).
   PubMedGoogle Scholar
• Sen A , HerediaN , SenutMCet al. Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren . Sci. Rep.5 , 14466 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Li Y , XieC , MurphySKet al. Lead exposure during early human development and DNA methylation of imprinted gene regulatory elements in adulthood . Environ. Health Perspect.124 ( 5 ), 666 – 673 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Sen A , HerediaN , SenutMCet al. Early life lead exposure causes gender-specific changes in the DNA methylation profile of DNA extracted from dried blood spots . Epigenomics7 ( 3 ), 379 – 393 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Sen A , CingolaniP , SenutMCet al. Lead exposure induces changes in 5-hydroxymethylcytosine clusters in CpG islands in human embryonic stem cells and umbilical cord blood . Epigenetics10 ( 7 ), 607 – 621 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Senut MC , CingolaniP , SenAet al. Epigenetics of early-life lead exposure and effects on brain development . Epigenomics4 ( 6 ), 665 – 674 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Sanders AP , SmeesterL , RojasDet al. Cadmium exposure and the epigenome: exposure-associated patterns of DNA methylation in leukocytes from mother–baby pairs . Epigenetics9 ( 2 ), 212 – 221 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Kippler M , EngstromK , MlakarSJet al. Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight . Epigenetics8 ( 5 ), 494 – 503 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Schneider JS , KiddSK , AndersonDW . Influence of developmental lead exposure on expression of DNA methyltransferases and methyl cytosine-binding proteins in hippocampus . Toxicol. Lett.217 ( 1 ), 75 – 81 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Nye MD , HoyoC , MurphySK . In vitro lead exposure changes DNA methylation and expression of IGF2 and PEG1/MEST . Toxicol. In vitro29 ( 3 ), 544 – 550 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Wright RO , SchwartzJ , WrightRJet al. Biomarkers of lead exposure and DNA methylation within retrotransposons . Environ. Health Perspect.118 ( 6 ), 790 – 795 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Pilsner JR , HuH , EttingerAet al. Influence of prenatal lead exposure on genomic methylation of cord blood DNA . Environ. Health Perspect.117 ( 9 ), 1466 – 1471 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Bellinger D , LevitonA , WaternauxC , NeedlemanH , RabinowitzM . Longitudinal analyses of prenatal and postnatal lead exposure and early cognitive development . N. Engl. J. Med.316 ( 17 ), 1037 – 1043 ( 1987 ).
   PubMed Web of Science ®Google Scholar
• Bellinger DC . Very low lead exposures and children’s neurodevelopment . Curr. Opin. Pediatr.20 ( 2 ), 172 – 177 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Ciesielski T , WeuveJ , BellingerDC , SchwartzJ , LanphearB , WrightRO . Cadmium exposure and neurodevelopmental outcomes in U.S. children . Environ. Health Perspect.120 ( 5 ), 758 – 763 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• De Groot CJ , Van Den AkkerEL , RingsEH , Delemarre-Van De WaalHA , Van Der GrondJ . Brain structure, executive function and appetitive traits in adolescent obesity . Pediatr. Obes. doi:10.1111/ijpo.12149 ( 2016 ) ( Epub ahead of print ).
   PubMed Web of Science ®Google Scholar
• Tsai CL , ChenFC , PanCY , TsengYT . The neurocognitive performance of visuospatial attention in children with obesity . Front. Psychol.7 , 1033 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Aitlhadj L , AvilaDS , BenedettoA , AschnerM , SturzenbaumSR . Environmental exposure, obesity and Parkinson’s disease: lessons from fat and old worms . Environ. Health Perspect.119 ( 1 ), 20 – 28 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Stansfield KH , PilsnerJR , LuQ , WrightRO , GuilarteTR . Dysregulation of BDNF–TrkB signaling in developing hippocampal neurons by Pb(2+): implications for an environmental basis of neurodevelopmental disorders . Toxicol. Sci.127 ( 1 ), 277 – 295 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Weston HI , WestonDD , AllenJL , Cory-SlechtaDA . Sex-dependent impacts of low-level lead exposure and prenatal stress on impulsive choice behavior and associated biochemical and neurochemical manifestations . Neurotoxicology44 , 169 – 183 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• An JJ , LiaoGY , KinneyCE , SahibzadaN , XuB . Discrete BDNF neurons in the paraventricular hypothalamus control feeding and energy expenditure . Cell Metab.22 ( 1 ), 175 – 188 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Kaur S , GonzalesMM , TarumiTet al. Serum brain-derived neurotrophic factor mediates the relationship between abdominal adiposity and executive function in middle age . J. Int. Neuropsychol. Soc.22 ( 5 ), 493 – 500 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Huang S , HuH , SanchezBNet al. Childhood blood lead levels and symptoms of attention deficit hyperactivity disorder (ADHD): a cross-sectional study of mexican children . Environ. Health Perspect.124 ( 6 ), 868 – 874 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Luo M , XuY , CaiRet al. Epigenetic histone modification regulates developmental lead exposure induced hyperactivity in rats . Toxicol. Lett.225 ( 1 ), 78 – 85 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Cortese S , Moreira-MaiaCR , St FleurD , Morcillo-PenalverC , RohdeLA , FaraoneSV . Association between ADHD and obesity: a systematic review and meta-analysis . Am. J. Psychiatry173 ( 1 ), 34 – 43 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Adnani L , LangevinLM . Zac1 regulates the differentiation and migration of neocortical neurons via Pac1 . 35 ( 39 ), 13430 – 13447 ( 2015 ).
   Google Scholar
• Butte NF , LiuY , ZakeriIFet al. Global metabolomic profiling targeting childhood obesity in the Hispanic population . Am. J. Clin. Nutr.102 ( 2 ), 256 – 267 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Cho K , MoonJS , KangJHet al. Combined untargeted and targeted metabolomic profiling reveals urinary biomarkers for discriminating obese from normal-weight adolescents . Pediatr. Obes. doi:10.1111/ijpo.12114 ( 2016 ) ( Epub ahead of print ).
   PubMed Web of Science ®Google Scholar
• Laura Anca P , BogdanaV , OliviaT , HoriaV , DumitruO , LeonZ . The relations between immunity, oxidative stress and inflammation markers, in childhood obesity . Free Radic. Biol. Med.75 ( Suppl. 1 ), S44 – S45 ( 2014 ).
   PubMedGoogle Scholar
• Kippler M , HossainMB , LindhCet al. Early life low-level cadmium exposure is positively associated with increased oxidative stress . Environ. Res.112 , 164 – 170 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Pizzino G , BittoA , InterdonatoMet al. Oxidative stress and DNA repair and detoxification gene expression in adolescents exposed to heavy metals living in the Milazzo-Valle del Mela area (Sicily, Italy) . Redox Biol.2 , 686 – 693 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Agnihotri SK , AgrawalU , GhoshI . Brain most susceptible to cadmium induced oxidative stress in mice . J. Trace Elem. Med. Biol.30 , 184 – 193 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Claus SP , GuillouH , Ellero-SimatosS . The gut microbiota: a major player in the toxicity of environmental pollutants?Npj Biofilms Microbiomes2 , 16003 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Schele E , GrahnemoL , AnestenF , HallenA , BackhedF , JanssonJO . Regulation of body fat mass by the gut microbiota: possible mediation by the brain . Peptides77 , 54 – 59 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Mayer EA , TillischK , GuptaA . Gut/brain axis and the microbiota . J. Clin. Invest.125 ( 3 ), 926 – 938 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Kumar H , LundR , LaihoAet al. Gut microbiota as an epigenetic regulator: pilot study based on whole-genome methylation analysis . mBio5 ( 6 ), e02113 – e02114 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Dietrich KN , WareJH , SalganikMet al. Effect of chelation therapy on the neuropsychological and behavioral development of lead-exposed children after school entry . Pediatrics114 ( 1 ), 19 – 26 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Van Oostdam J , DonaldsonSG , FeeleyMet al. Human health implications of environmental contaminants in Arctic Canada: a review . Sci. Total Environ. 351–352 , 165 – 246 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Senut MC , SenA , CingolaniPet al. Lead exposure disrupts global DNA methylation in human embryonic stem cells and alters their neuronal differentiation . Toxicol. Sci.139 ( 1 ), 142 – 161 ( 2014 ).
   PubMed Web of Science ®Google Scholar