title: The Transcriptional Effects of PCB118 and PCB153 on the Liver, Adipose Tissue, Muscle and Colon of Mice: Highlighting of Glut4 and Lipin1 as Main Target Genes for PCB Induced Metabolic Disorders.
abstract: Epidemiological studies have associated environmental exposure to polychlorinated biphenyls (PCBs) with an increased risk of type 2 diabetes; however, little is known about the underlying mechanisms involved in the metabolic side-effects of PCB. Our study evaluated the transcriptional effects of a subchronic exposure (gavage at Day 0 and Day 15 with 10 or 100 μmol/Kg bw) to PCB118 (dioxin-like PCB), PCB153 (non-dioxin-like PCB), or an equimolar mixture of PCB118 and PCB153 on various tissues (liver, visceral adipose tissue, muscle, and colon) in mice. Our results showed that a short-term exposure to PCB118 and/or PCB153 enhanced circulating triglyceride levels but did not affect glycemia. Among the studied tissues, we did not observe any modification of the expression of inflammation-related genes, such as cytokines or chemokines. The main transcriptional effects were observed in visceral adipose and liver tissues. We found a downregulation of lipin1 and glut4 expression in these two target organs. In adipose tissue, we also showed a downregulation of Agpat2, Slc25a1, and Fasn. All of these genes are involved in lipid metabolism and insulin resistance. In muscles, we observed an induction of CnR1 and Foxo3 expression, which may be partly involved in PCB metabolic effects. In summary, our results suggest that lipin1 and glut4, notably in adipose tissue, are the main targeted genes in PCB-induced metabolic disorders, however, further studies are required to fully elucidate the mechanisms involved.
authors.affiliation: IMBE (Institut Méditerranéen de Biodiversité et d'Ecologie Marine et Continentale), UMR CNRS 7263, IRD 237 Aix-Marseille Université Avignon Université, Campus Timone, Faculté de Pharmacie, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Mesnier
authors.affiliation: IMBE (Institut Méditerranéen de Biodiversité et d'Ecologie Marine et Continentale), UMR CNRS 7263, IRD 237 Aix-Marseille Université Avignon Université, Campus Timone, Faculté de Pharmacie, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Champion
authors.affiliation: UMR S 910 Génétique Médicale et Génomique Fonctionnelle, Campus Timone, Faculté de Médecine, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Louis
authors.affiliation: IMBE (Institut Méditerranéen de Biodiversité et d'Ecologie Marine et Continentale), UMR CNRS 7263, IRD 237 Aix-Marseille Université Avignon Université, Campus Timone, Faculté de Pharmacie, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Sauzet
authors.affiliation: IMBE (Institut Méditerranéen de Biodiversité et d'Ecologie Marine et Continentale), UMR CNRS 7263, IRD 237 Aix-Marseille Université Avignon Université, Campus Timone, Faculté de Pharmacie, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Phealay
authors.initials: P
authors.lastname: May
authors.affiliation: UMR INSERM 1062, INRA 1260, Nutrition, Obésité et Risque Thrombotique (NORT), Aix-Marseille Université Campus Timone, Faculté de Médecine, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Portugal
authors.affiliation: IMBE (Institut Méditerranéen de Biodiversité et d'Ecologie Marine et Continentale), UMR CNRS 7263, IRD 237 Aix-Marseille Université Avignon Université, Campus Timone, Faculté de Pharmacie, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Benbrahim
authors.affiliation: IMBE (Institut Méditerranéen de Biodiversité et d'Ecologie Marine et Continentale), UMR CNRS 7263, IRD 237 Aix-Marseille Université Avignon Université, Campus Timone, Faculté de Pharmacie, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Abraldes
authors.affiliation: UMR INSERM 1062, INRA 1260, Nutrition, Obésité et Risque Thrombotique (NORT), Aix-Marseille Université Campus Timone, Faculté de Médecine, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.affiliation: UMR INSERM 1062, INRA 1260, Nutrition, Obésité et Risque Thrombotique (NORT), Aix-Marseille Université Campus Timone, Faculté de Médecine, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Marie-Josephe
authors.initials: MJ
authors.lastname: Amiot-Carlin
authors.affiliation: UMR INSERM 1062, INRA 1260, Nutrition, Obésité et Risque Thrombotique (NORT), Aix-Marseille Université Campus Timone, Faculté de Médecine, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Peiretti
authors.affiliation: IMBE (Institut Méditerranéen de Biodiversité et d'Ecologie Marine et Continentale), UMR CNRS 7263, IRD 237 Aix-Marseille Université Avignon Université, Campus Timone, Faculté de Pharmacie, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Piccerelle
authors.affiliation: UMR INSERM 1062, INRA 1260, Nutrition, Obésité et Risque Thrombotique (NORT), Aix-Marseille Université Campus Timone, Faculté de Médecine, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Nalbone
authors.affiliation: IMBE (Institut Méditerranéen de Biodiversité et d'Ecologie Marine et Continentale), UMR CNRS 7263, IRD 237 Aix-Marseille Université Avignon Université, Campus Timone, Faculté de Pharmacie, 27 Boulevard Jean Moulin, F-13385, Marseille cedex 05, France.
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Villard
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051275:Glucose Transporter Type 4 / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D010711:Phosphatidate Phosphatase / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000009:adverse effects*; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D009687:Nuclear Proteins; C495693:Slc2a4 protein, mouse; D014280:Triglycerides; C070055:2,3',4,4',5-pentachlorobiphenyl; D011078:Polychlorinated Biphenyls; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase; C014024:2,4,5,2',4',5'-hexachlorobiphenyl