Sex and Exposure to Postnatal Chlorpyrifos Influence the Epigenetics of Feeding-Related Genes in a Transgenic APOE Mouse Model: Long-Term Implications on Body Weight after a High-Fat Diet

Laia Guardia-Escote, Jordi Blanco, Pia Basaure, Judit Biosca-Brull, Rikst Nynke Verkaik-Schakel, Maria Cabré, Fiona Peris-Sampedro, Cristian Pérez-Fernández, Fernando Sánchez-Santed, Torsten Plösch, José L. Domingo and Maria Teresa Colomina
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Laia Guardia-Escote: Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, 43007 Tarragona, Spain
Jordi Blanco: Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, 43007 Tarragona, Spain
Pia Basaure: Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, 43007 Tarragona, Spain
Judit Biosca-Brull: Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, 43007 Tarragona, Spain
Rikst Nynke Verkaik-Schakel: Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
Maria Cabré: Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, 43007 Tarragona, Spain
Fiona Peris-Sampedro: Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 405 30 Gothenburg, Sweden
Cristian Pérez-Fernández: Department of Psychology and Health Research Center (CEINSA), Almeria University-ceiA3, 04120 Almeria, Spain
Fernando Sánchez-Santed: Department of Psychology and Health Research Center (CEINSA), Almeria University-ceiA3, 04120 Almeria, Spain
Torsten Plösch: Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
José L. Domingo: Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, 43201 Reus, Spain
Maria Teresa Colomina: Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, 43007 Tarragona, Spain

IJERPH, 2020, vol. 18, issue 1, 1-17

Abstract: Developmental exposure to toxicants and diet can interact with an individual’s genetics and produce long-lasting metabolic adaptations. The different isoforms of the apolipoprotein E ( APOE ) are an important source of variability in metabolic disorders and influence the response to the pesticide chlorpyrifos (CPF). We aimed to study the epigenetic regulation on feeding control genes and the influence of postnatal CPF exposure, APOE genotype, and sex, and how these modifications impact on the metabolic response to a high-fat diet (HFD). Both male and female apoE3- and apoE4-TR mice were exposed to CPF on postnatal days 10–15. The DNA methylation pattern of proopiomelanocortin, neuropeptide Y, leptin receptor, and insulin-like growth factor 2 was studied in the hypothalamus. At adulthood, the mice were given a HFD for eight weeks. The results highlight the importance of sex in the epigenetic regulation and the implication of CPF treatment and APOE genotype. The body weight progression exhibited sex-dimorphic differences, apoE4-TR males being the most susceptible to the effects induced by CPF and HFD. Overall, these results underscore the pivotal role of sex, APOE genotype, and developmental exposure to CPF on subsequent metabolic disturbances later in life and show that sex is a key variable in epigenetic regulation.

Keywords: chlorpyrifos; APOE; epigenetics; feeding control; high-fat diet (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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