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 Cabre, Fiona Peris-Sampedro, Cristian Perez-Fernandez, Fernando Sanchez-Santed, Torsten Plosch, Jose L. Domingo, Maria Teresa Colomina*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Downloads (Pure)

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.

Original languageEnglish
Article number184
Pages (from-to)1-17
Number of pages17
JournalInternational Journal of Environmental Research and Public Health
Volume18
Issue number1
DOIs
Publication statusPublished - Jan-2021

Keywords

  • chlorpyrifos
  • APOE
  • epigenetics
  • feeding control
  • high-fat diet
  • NERVOUS-SYSTEM CONTROL
  • APOLIPOPROTEIN-E
  • DNA METHYLATION
  • DEVELOPMENTAL EXPOSURE
  • TARGETED REPLACEMENT
  • INDUCED OBESITY
  • FOOD-INTAKE
  • ORGANOPHOSPHORUS INSECTICIDES
  • PROMOTER METHYLATION
  • PESTICIDE EXPOSURE

Cite this