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

Autor: Mesnier, Aurélia, Champion, Serge, Louis, Laurence, Sauzet, Christophe, May, Phealay, Portugal, Henri, Benbrahim, Karim, Abraldes, Joelle, Alessi, Marie-Christine, Amiot-Carlin, Marie-Josephe, Peiretti, Franck, Piccerelle, Philippe, Nalbone, Gilles, Villard, Pierre-Henri
Přispěvatelé: Institut méditerranéen de biodiversité et d'écologie marine et continentale ( IMBE ), Université d'Avignon et des Pays de Vaucluse ( UAPV ) -Aix Marseille Université ( AMU ) -Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique ( CNRS ), Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Nutrition, obésité et risque thrombotique ( NORT ), Institut National de la Recherche Agronomique ( INRA ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire central, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Villard, Pierre-Henri, This work was supported by the PNRPE (Plan National de Recherche sur les Perturbateurs Endocriniens) from the 'Ministère de l'écologie, du développement durable et de l'énergie', Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université (AMU)-Avignon Université (AU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Blood Glucose
Male
EXPRESSION
Transcription
Genetic
Colon
Phosphatidate Phosphatase
lcsh:Medicine
Real-Time Polymerase Chain Reaction
Mice
Metabolic Diseases
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
POLYCHLORINATED-BIPHENYLS
[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology
Animals
EXPOSURE
Muscle
Skeletal
lcsh:Science
Triglycerides
Oligonucleotide Array Sequence Analysis
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
LIPODYSTROPHY
[ SDV.BID ] Life Sciences [q-bio]/Biodiversity
INSULIN-RESISTANCE
Glucose Transporter Type 4
ADIPOCYTE DIFFERENTIATION
Dose-Response Relationship
Drug
[ SDV ] Life Sciences [q-bio]
lcsh:R
DEATH
Nuclear Proteins
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
GAMMA
Polychlorinated Biphenyls
TRANSPORT
Mice
Inbred C57BL
[SDV.TOX] Life Sciences [q-bio]/Toxicology
Adipose Tissue
Liver
[SDV.TOX]Life Sciences [q-bio]/Toxicology
OBESITY
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
lcsh:Q
Research Article
Zdroj: PLoS ONE
PLoS ONE, Public Library of Science, 2015, 〈10.1371/journal.pone.0128847〉
PLoS ONE, Public Library of Science, 2015, 10 (6), pp.e0128847. ⟨10.1371/journal.pone.0128847⟩
PLoS ONE, 2015, 10 (6), pp.e0128847. ⟨10.1371/journal.pone.0128847⟩
PLoS ONE, Vol 10, Iss 6, p e0128847 (2015)
ISSN: 1932-6203
Popis: International audience; Epidemiological studies have associated environmental exposure to polychlorinated biphe-nyls (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 equi-molar 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 downregu-lation 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.
Databáze: OpenAIRE
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