title: Unraveling the mode of action of an obesogen: mechanistic analysis of the model obesogen tributyltin in the 3T3-L1 cell line.
abstract: Obesogenic compounds are chemicals that have an influence on obesity development. This study was designed to unravel the molecular mechanisms of the model obesogen TBT, using microarray analysis in the 3T3-L1 in vitro system, and to evaluate the use of toxicogenomics for obesogen screening. The microarray results revealed enrichment of Gene Ontology terms involved in energy and fat metabolism after 10 days of TBT exposure. Pathway analysis unveiled PPAR signalling pathway as the sole pathway significantly enriched after 1 day and the most significantly enriched pathway after 10 days of exposure. To our knowledge, this is the first study delivering an in depth mechanistic outline of the mode of action of TBT as an obesogen, combining effects on both cell physiological and gene expression level. Furthermore, our results show that combining transcriptomics with 3T3-L1 cells is a promising tool for screening of potential obesogenic compounds.
authors: Systemic Physiological and Ecotoxicological Research (SPHERE), Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerpen, Belgium. Anna.Pereira-Fernandes@ua.ac.be
authors: Anna
authors: A
authors: Pereira-Fernandes
authors: Caroline
authors: C
authors: Vanparys
authors: Tine L M
authors: TL
authors: Hectors
authors: Lucia
authors: L
authors: Vergauwen
authors: Dries
authors: D
authors: Knapen
authors: Philippe G
authors: PG
authors: Jorens
authors: Ronny
authors: R
authors: Blust
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D054392:Adipokines / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D004967:Estrogens / Q000378:metabolism; D015870:Gene Expression; D005938:Glucocorticoids / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D009765:Obesity / Q000139:chemically induced*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D015398:Signal Transduction; D014220:Trialkyltin Compounds / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D054392:Adipokines; D004967:Estrogens; D005938:Glucocorticoids; D047492:Peroxisome Proliferator-Activated Receptors; D014220:Trialkyltin Compounds; D014280:Triglycerides; D051153:Wnt Proteins; C011559:tributyltin; D002784:Cholesterol