title: Adulthood dietary exposure to a common pesticide leads to an obese-like phenotype and a diabetic profile in apoE3 mice.
abstract: Increasing evidence links the widespread exposure to organophosphate (OP) pesticides to the global epidemics of type 2 diabetes and obesity. Our recent data highlighted gene×environment interactions: mice expressing the human apolipoprotein E3 (apoE3) isoform were more prone to develop obesity than those expressing apoE2 or apoE4 upon dietary challenge with chlorpyrifos (CPF), the most used OP worldwide. Thus, we aimed to further explore the contribution of the APOE3 genotype on the emergence of obesity and related metabolic dysfunctions upon subchronic exposure to CPF. Seven-month-old targeted replacement apoE3 and C57BL/6N male mice were orally exposed to CPF at 0 or 2mg/kg body weight/day for 8 consecutive weeks. We examined body weight status, food and water intake, lipid and glucose homeostasis, metabolic biomarkers concentrations, insulin levels and insulin resistance, and leptin and ghrelin profiles. CPF exposure generally increased food ingestion, glucose and total cholesterol concentrations, and tended to elevate acyl ghrelin levels. Nonetheless, excess weight gain and increased leptin levels were inherent to apoE3 mice. Moreover, the propensity towards a diabetic profile was markedly higher in these animals than in C57BL/6N, as they showed a higher homeostatic model assessment for insulin resistance index and higher insulin levels. Although both genotypes were metabolically affected by CPF, the results of the present investigation revealed that apoE3 mice were the most vulnerable to developing obesity and related disturbances following CPF administration through the diet. Since the APOE3 genotype is the most prevalent worldwide, current findings have particular implications for human health.
authors.affiliation: Research in Neurobehaviour and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Department of Psychology and Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain; Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Fiona
authors.initials: F
authors.lastname: Peris-Sampedro
authors.affiliation: Research in Neurobehaviour and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Cabré
authors.affiliation: Research in Neurobehaviour and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Department of Psychology and Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain; Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Pia
authors.initials: P
authors.lastname: Basaure
authors.affiliation: Research in Neurobehaviour and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Reverte
authors.affiliation: Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Domingo
authors.affiliation: Research in Neurobehaviour and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Department of Psychology and Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain; Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Reus, Spain. Electronic address: mariateresa.colomina@urv.cat.
authors.forename: Maria
authors.initials: M
authors.lastname: Teresa Colomina
mesh_terms: D000818:Animals; D053318:Apolipoprotein E3 / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D004390:Chlorpyrifos / Q000633:toxicity*; D002784:Cholesterol / Q000097:blood; D002802:Cholinesterases / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood*; D004032:Diet; D004435:Eating; D054439:Ghrelin / Q000097:blood; D007306:Insecticides / Q000633:toxicity*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000097:blood*; D010641:Phenotype; D014280:Triglycerides / Q000097:blood
chemical_list: D053318:Apolipoprotein E3; D001786:Blood Glucose; D054439:Ghrelin; D007306:Insecticides; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D002784:Cholesterol; D002802:Cholinesterases; D004390:Chlorpyrifos
keywords: Apolipoprotein E; Diabetes; Ghrelin; Leptin; Obesity; Pesticide