TY - JOUR
T1 - Sex and Exposure to Postnatal Chlorpyrifos Influence the Epigenetics of Feeding-Related Genes in a Transgenic APOE Mouse Model
T2 - Long-Term Implications on Body Weight after a High-Fat Diet
AU - Guardia-Escote, Laia
AU - Blanco, Jordi
AU - Basaure, Pia
AU - Biosca-Brull, Judit
AU - Verkaik-Schakel, Rikst Nynke
AU - Cabre, Maria
AU - Peris-Sampedro, Fiona
AU - Perez-Fernandez, Cristian
AU - Sanchez-Santed, Fernando
AU - Plosch, Torsten
AU - Domingo, Jose L.
AU - Colomina, Maria Teresa
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - chlorpyrifos
KW - APOE
KW - epigenetics
KW - feeding control
KW - high-fat diet
KW - NERVOUS-SYSTEM CONTROL
KW - APOLIPOPROTEIN-E
KW - DNA METHYLATION
KW - DEVELOPMENTAL EXPOSURE
KW - TARGETED REPLACEMENT
KW - INDUCED OBESITY
KW - FOOD-INTAKE
KW - ORGANOPHOSPHORUS INSECTICIDES
KW - PROMOTER METHYLATION
KW - PESTICIDE EXPOSURE
U2 - 10.3390/ijerph18010184
DO - 10.3390/ijerph18010184
M3 - Article
VL - 18
SP - 1
EP - 17
JO - International Journal of Environmental Research and Public Health
JF - International Journal of Environmental Research and Public Health
SN - 1661-7827
IS - 1
M1 - 184
ER -