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

• Published in: PloS one Vol. 10; no. 6; p. e0128847
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.06.2015; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; Bioaccumulation; Biochemistry, Molecular Biology; Blood glucose; Blood Glucose - drug effects; Body fat; Chemokines; Chlorocarbons; Colon; Colon - drug effects; Colon - metabolism; Cytokines; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Dioxin; Dioxins; Disorders; Dose-Response Relationship, Drug; Ecological risk assessment; Endocrinology and metabolism; Epidemiology; Exposure; Fatty acids; FOXO3 protein; Gene expression; Genes; Genetic aspects; Genomics; Glucose Transporter Type 4 - drug effects; Health risks; Homeostasis; House mouse; Human health and pathology; Insulin; Insulin resistance; Life Sciences; Lipid metabolism; Liver; Liver - drug effects; Liver - metabolism; Male; Metabolic Diseases - chemically induced; Metabolic disorders; Metabolism; Mice; Mice, Inbred C57BL; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscles; Nuclear Proteins - drug effects; Nutrition; Oligonucleotide Array Sequence Analysis; Organs; PCB; PCB compounds; Phosphatidate Phosphatase - drug effects; Polychlorinated biphenyls; Polychlorinated Biphenyls - adverse effects; Proteins; Real-Time Polymerase Chain Reaction; Rodents; Toxicology; Transcription; Transcription (Genetics); Transcription factors; Transcription, Genetic - drug effects; Triglycerides; Triglycerides - blood; Type 2 diabetes; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0128847

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.