Towards a humanized PPARγ reporter system for in vivo screening of obesogens

Overeating and lack of exercise are major contributors to the current obesity epidemic, but environmental contaminants, or obesogens, are also considered to be potential actors. A common obesogen target is the Peroxisome Proliferator Activated Receptor Gamma (PPAR gamma). Screening for exogenous obesogens requires in vivo systems as many xenobiotics exert their effects through metabolites. We thus developed a humanized in vivo PPAR gamma reporter model, using Xenopus laevis larvae, a species possessing metabolic capacities comparable to mammals. A somatic transgenesis approach was used to co-express an expression vector for the human PPAR gamma protein simultaneously with one of a series of reporter vectors, each containing a PPAR gamma Response Element (PPRE)-eGFP sequence. Treatment of tadpoles with PPAR gamma agonists, antagonists or candidate obesogens, significantly modulated eGFP expression. Thus, the system provides a promising proof of principle for a sensitive and reliable humanized in vivo tool to screen both novel PPAR gamma drug ligands and potential endocrine disruptors or obesogens targeting this receptor. (c) 2013 Elsevier Ireland Ltd. All rights reserved.