title: Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease.
abstract: Millions of Mexico, US and across the world children are overweight and obese. Exposure to fossil-fuel combustion sources increases the risk for obesity and diabetes, while long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with increased risk of Alzheimer's disease (AD). Mexico City Metropolitan Area children are chronically exposed to PM2.5 and O3 concentrations above the standards and exhibit systemic, brain and intrathecal inflammation, cognitive deficits, and Alzheimer disease neuropathology. We investigated adipokines, food reward hormones, endothelial dysfunction, vitamin D and apolipoprotein E (APOE) relationships in 80 healthy, normal weight 11.1±3.2 year olds matched by age, gender, BMI and SES, low (n: 26) versus high (n:54) PM2.5 exposures. Mexico City children had higher leptin and endothelin-1 (p<0.01 and p<0.000), and decreases in glucagon-like peptide-1 (GLP 1), ghrelin, and glucagon (<0.02) versus controls. BMI and leptin relationships were significantly different in low versus high PM2.5 exposed children. Mexico City APOE 4 versus 3 children had higher glucose (p=0.009). Serum 25-hydroxyvitamin D<30 ng/mL was documented in 87% of Mexico City children. Leptin is strongly positively associated to PM 2.5 cumulative exposures. Residing in a high PM2.5 and O3 environment is associated with 12h fasting hyperleptinemia, altered appetite-regulating peptides, vitamin D deficiency, and increases in ET-1 in clinically healthy children. These changes could signal the future trajectory of urban children towards the development of insulin resistance, obesity, type II diabetes, premature cardiovascular disease, addiction-like behavior, cognitive impairment and Alzheimer's disease. Increased efforts should be made to decrease pediatric PM2.5 exposures, to deliver health interventions prior to the development of obesity and to identify and mitigate environmental factors influencing obesity and Alzheimer disease.
authors.affiliation: The Center for Structural and Functional Neurosciences, The University of Montana, Missoula, MT 59812, USA; Hospital Central Militar, Mexico City 11649, Mexico. Electronic address: lilian.calderon-garciduenas@umontana.edu.
authors.forename: Lilian
authors.initials: L
authors.lastname: Calderón-Garcidueñas
authors.affiliation: Hospital Central Militar, Mexico City 11649, Mexico.
authors.forename: Maricela
authors.initials: M
authors.lastname: Franco-Lira
authors.affiliation: Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada K1S 5B6.
authors.forename: Amedeo
authors.initials: A
authors.lastname: D'Angiulli
authors.affiliation: Escuela de Ciencias de la Salud, Universidad del Valle de México, Saltillo, Coahuila 25204, Mexico.
authors.forename: Joel
authors.initials: J
authors.lastname: Rodríguez-Díaz
authors.affiliation: Clinical and Environmental Laboratory Micro Trace Minerals (MTM), 91217 Hersbruck, Germany.
authors.forename: Eleonore
authors.initials: E
authors.lastname: Blaurock-Busch
authors.affiliation: Clinical and Environmental Laboratory Micro Trace Minerals (MTM), 91217 Hersbruck, Germany.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Busch
authors.affiliation: The Center for Structural and Functional Neurosciences, The University of Montana, Missoula, MT 59812, USA.
authors.forename: Chih-kai
authors.initials: CK
authors.lastname: Chao
authors.affiliation: The Center for Structural and Functional Neurosciences, The University of Montana, Missoula, MT 59812, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Thompson
authors.affiliation: Mathematics Department, Boise State University, Boise, Idaho, USA.
authors.forename: Partha S
authors.initials: PS
authors.lastname: Mukherjee
authors.affiliation: Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, 04510, Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torres-Jardón
authors.affiliation: College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: George
authors.initials: G
authors.lastname: Perry
mesh_terms: D000293:Adolescent; D000544:Alzheimer Disease / Q000503:physiopathology*; D001835:Body Weight; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D019332:Endothelin-1 / Q000097:blood*; D006728:Hormones / Q000502:physiology*; D006801:Humans; D020738:Leptin / Q000097:blood*; D008800:Mexico; D009765:Obesity / Q000503:physiopathology*; D052638:Particulate Matter / Q000633:toxicity*; D014808:Vitamin D Deficiency / Q000139:chemically induced*
chemical_list: D019332:Endothelin-1; D006728:Hormones; D020738:Leptin; D052638:Particulate Matter
keywords: APOE; Alzheimer; Children; Fructose; Leptin; Mexico City; Obesity; PM(2.5) Air pollution; Vitamin D