| Obesity is a serious health risk that has grown to epidemic proportions globally. Obesity has historically been considered a disorder of energy imbalance (too much intake, too little expenditure) imposed on a background of genetic disposition. Increasing evidence exists, however, which shows that nutritional and environmental factors during early life influence the development of obesity in the long term. In particular, early developmental exposures to environmental chemicals may play a role in the onset of adult obesity. While the underlying mechanisms are unclear, environmental chemicals may disturb epigenetic, structural and functional adaptive responses responsible for regulating energy metabolism and adipogenesis. In this project I will test the hypothesis that early exposure to environmental chemicals leads to adult onset of obesity, which may also be passed on over generations. I will use the zebrafish Danio rerio for the first time for this purpose. The zebrafish is one of the most important models in environmental toxicology and developmental biology, and is rapidly becoming a major model for studies in human health and disease. The potential to perform high throughput screens in the zebrafish embryo will allow me to develop methods to rapidly test environmental chemicals for their obesogenic potential. I will determine causality and multigenerational effects of early exposure, as well as examine the molecular targets and cellular mechanisms underlying obesogenic effects of environmental chemicals. The simultaneous execution of this project together with a newly awarded EU project on obesity gives me the exciting opportunity to compare the established mouse model for obesity with this up-and-coming zebrafish model. Given the health implications of obesity and the related drain on health care systems worldwide, my proposed research has a high potential impact in terms of identifying chemicals with obesogenic effects and identification of risk factors involved in the development of this disorder. |
