The OBELIX project: early life exposure to endocrine disruptors and obesity

Abstract

The hypothesis of whether early life exposure (both pre- and early postnatal) to endocrine-disrupting chemicals (EDCs) may be a risk factor for obesity and related metabolic diseases later in life will be tested in the European research project OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life). OBELIX is a 4-y project that started in May 2009 and which has the following 5 main objectives: 1) to assess early life exposure in humans to major classes of EDCs identified as potential inducers of obesity (ie, dioxin-like compounds, non-dioxin-like polychlorinated biphenyls, organochlorine pesticides, brominated flame retardants, phthalates, and perfluorinated compounds) by using mother-child cohorts from 4 European regions with different food-contaminant exposure patterns; 2) to relate early life exposure to EDCs with clinical markers, novel biomarkers, and health-effect data related to obesity; 3) to perform hazard characterization of early life exposure to EDCs for the development of obesity later in life by using a mouse model; 4) to determine mechanisms of action of obesogenic EDCs on developmental programming with in vivo and in vitro genomics and epigenetic analyses; and 5) to perform risk assessments of prenatal exposure to obesogenic EDCs in food by integrating maternal exposure through food-contaminant exposure and health-effect data in children and hazard data in animal studies.

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

“…During this period of life, and more specifically during embryonic gonadal sex determination, chemicals can exert effects at very low levels of exposure and may involve epigenetic events that could be transgenerationally transmitted (Anway et al, 2005). Hence, some research projects are studying the effects of these chemicals on obesity development, such as OBELIX (Legler et al, 2011), and will include epigenetic analyses in both animal models and children.…”

Biomarkers Linking PCB Exposure and Obesity.

“…boys were more susceptible than girls to growth restrictions [26]; (b) poor neurodevelopment, in which the results indicated an association of PCBs with decreased Mental Development Index (MDI), and reduced levels of thyroid hormone [27, 28]; hearing impairments, wherein the results showed that PCB exposures were associated with harmful effects on the outer hair cells of the cochlea [29]; endocrine disruption, characterized by an increase in the prevalence of several subclinical and overt thyroid and metabolic disorders [30, 112]; and diabetes, showing that increasing serum concentrations of individual POPs considerably increased the prevalence of pre-diabetics indicators [10]. …”

Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals

“…To test this, we challenged primary PBMC with five different endocrine disrupting chemicals (EDCs) and studied their gene expression response in vitro. The chemicals used in this experiment (PCB126, PCB153, BDE47, PFOA, and BPA) were chosen from major classes of EDCs that can be found as food contaminants (Legler et al, 2011). This study was set up as a screening experiment to find compound-specific gene expression profiles and search for obesity-related gene expression changes.…”