title: Towards a humanized PPARγ reporter system for in vivo screening of obesogens.
abstract: 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 (PPARγ). Screening for exogenous obesogens requires in vivo systems as many xenobiotics exert their effects through metabolites. We thus developed a humanized in vivo PPARγ 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 PPARγ protein simultaneously with one of a series of reporter vectors, each containing a PPARγ Response Element (PPRE)-eGFP sequence. Treatment of tadpoles with PPARγ 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 PPARγ drug ligands and potential endocrine disruptors or obesogens targeting this receptor.
authors.affiliation: UMR CNRS 7221, Evolution des Régulations Endocriniennes CNRS UMR 7221/Muséum National d'Histoire Naturelle, Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, 75231 Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Punzon
authors.forename: V
authors.initials: V
authors.lastname: Latapie
authors.forename: S
authors.initials: S
authors.lastname: Le Mével
authors.forename: A
authors.initials: A
authors.lastname: Hagneau
authors.forename: P
authors.initials: P
authors.lastname: Jolivet
authors.forename: K
authors.initials: K
authors.lastname: Palmier
authors.forename: J B
authors.initials: JB
authors.lastname: Fini
authors.forename: B A
authors.initials: BA
authors.lastname: Demeneix
mesh_terms: D000818:Animals; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007814:Larva / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D011075:Polybrominated Biphenyls / Q000494:pharmacology*; D020218:Response Elements; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014982:Xenopus laevis / Q000235:genetics* / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D011075:Polybrominated Biphenyls; D045162:Thiazolidinediones; C485184:enhanced green fluorescent protein; D000077154:Rosiglitazone; D049452:Green Fluorescent Proteins; D008071:Lipoprotein Lipase; D003066:Coenzyme A Ligases; C020806:tetrabromobisphenol A