title: The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals.
abstract: Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.
authors.affiliation: Institute for Environmental Studies Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
authors.forename: Jente
authors.initials: J
authors.lastname: Stel
authors.affiliation: Institute for Environmental Studies Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
authors.forename: Juliette
authors.initials: J
authors.lastname: Legler
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D019175:DNA Methylation / Q000187:drug effects; D004198:Disease Susceptibility; D052244:Endocrine Disruptors / Q000009:adverse effects*; D004781:Environmental Exposure; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018811:Maternal Exposure; D009765:Obesity / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014220:Trialkyltin Compounds / Q000009:adverse effects
chemical_list: D052244:Endocrine Disruptors; D014220:Trialkyltin Compounds; C011559:tributyltin