Characterization of peroxisome proliferator activated receptor (PPAR) pathways in the zebrafish (Danio rerio)

Peroxisome proliferator activated receptor (PPARs) are members of the of the nuclear hormone receptor superfamily and are implicated in a variety of fundamental biological processes such as lipid metablism, inflammation and cell differentiation. PPARs are ligand mediated transcription factors that can be activated by a group of structurally diverse man-made chemicals, the so called peroxisome prolferators (PPs). This class of PPAR ligands consists of - apart from natural and synthetic fatty acids - a vast amount of human pharmaceuticals (e.g. fibrates) and perfluoralkyl compounds (e.g. PFOS and PFOA), a “new” class of environmental pollutents of which only recently the importance and worldwide dispersion has been reported.
Since the early ’90 these receptors have been studied in an increasing amount of species, predominantly in mammals. Recently, PPARs have been identified in several teleosts. Given the involvement of PPARs in important biological processes such as lipid metabolism and glucose homeostasis, it is crucial to analyse the impact of PPAR-binding compounds in these species. Although currently little is known about the activation and action of PPAR-pathways in teleosts, new research developments enable the investigation of the importance of PPAR-pathways, additional regulation levels, and their functional interactions in fish.
In this project the molecular modes of action of PPAR-ligands in zebrafish are investigated using both in vitro and in vivo models. The goal of this research is to generate insight in molecular PPAR-pathways and their functional involvement in cellular and toxicological processes. Via this molecuar basis we want to better understand PPAR-mediated pathways and their funcional importance in teleosts. This fundamental insight will form the basis for a better risk assessment of PPs in the environment. Effects of in vivo exposure to PPs on e.g. behavior, reproduction and energy reserves will lead to insight in the biological relevance of PPAR-activation to higher levels of biological organisation.