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Newsletter No 4 December 2013

Four years of OBELIX research comes to an exciting end in Brussels


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The European Commission funded OBELIX project, coordinated by IVM, came to an exciting end in October at successful workshop in Brussels attended by over 60 stakeholders from academia, policy and industry. Researchers from 7 laboratories throughout Europe determined the exposure of the developing baby to contaminants and researched the link between exposure and health effects later in life.

OBELIX is an acronym for “OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life.” The research focused on a specific type of contaminants present in food, the so-called “endocrine disrupting chemicals” (EDCs). EDCs are chemicals that may mimic hormones and have negative effects on reproduction and other endocrine-mediated processes. EDCs are also suspected to promote obesity by disrupting metabolic and endocrine pathways involved in energy metabolism. Examples of EDCs include: dioxins, which are toxic chemicals formed during incineration; brominated flame retardants, which are used to treat electronic equipment; and perfluorinated compounds, which are used in many applications such as food packaging. EDCs are present in low concentrations in food and may be transferred to the developing baby. Previous studies indicate that early life exposure to EDCs may contribute to the incidence of overweight, and thus a number of EDCs have been called “obesogens” due to their potential to disturb normal development and balance of lipid metabolism.

OBELIX tested the hypothesis that early developmental exposure to EDCs leads to obesity later in life by combining toxicological and epidemiological studies. A series of five long-term animal studies were carried out, in which mice were exposed to EDCs through the diet during gestation and lactation. Offspring were monitored up to adulthood. Doses in animal experiments were generally below no adverse effect levels for developmental toxicity. Epidemiological studies involved mother-child cohorts from four European countries in which EDC exposure was determined in cord blood and milk samples using novel and sensitive chemical analytical methods. Growth and health status was followed up to 7 years. The project generated many results: fourteen publications have already been released (see website for list of publications), and at least 18 publications are in the final stages of preparation and submission for publication. Animal studies indicate divergent sex- and compound-specific effects of perinatal exposure on body weight. Mechanistic (in vitro) studies have shown that some EDCs enhance adipocyte differentiation, an effect that is accompanied by epigenetic changes, i.e. global DNA demethylation. Epidemiological studies revealed an inverse relationship between prenatal polychlorinated biphenyl (PCB) exposure and birth weight, and indicate differences in pre- and postnatal exposure on growth trajectories in children. In some cases in both animal and human studies, some EDCs showed effects in the direction opposite than hypothesized. Importantly, the OBELIX project concluded that perinatal exposure to low levels of EDCs affects endocrine signalling pathways that may lead to changes in body weight.

In the words of Dr. Matt Longnecker, epidemiologist at NIEHS, U.S.A. and independent scientific advisor to OBELIX: “The overall vision for the project was impressive: create an interdisciplinary team of scientists who would generate new data on the toxicology, molecular mechanisms, epidemiology, and risk implications of a panel of obesogens…The goals were ambitious but nonetheless relentlessly and cheerfully pursued to much success.  The project was a model of how scientific questions should be pursued—holistically”.

The implications of the results of the OBELIX project and related issues of potential risks of exposure to EDCs will be discussed in Zembla, a documentary on Dutch television to be aired on December 19, 2013.

For more information on OBELIX visit www.theobelixproject.org, or contact the project coordinator Juliette.legler@vu.nl

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