title: Liver metabolic disruption induced after a single exposure to PCB126 in rats.
abstract: Polychlorinated biphenyls (PCBs) have been recognized as metabolic disruptors. The liver plays a pivotal role in detoxification of an organism. Fatty liver results from altered intra-, and extra-hepatic mediators and is associated with increased glucose-related protein 78 (GRP78), commonly used as a marker for endoplasmic reticulum (ER) stress signaling. This pilot study aimed to study the effects of a single exposure on fatty liver metabolic parameters. The objective of the study is to characterize the effects of 3,3',4,4',5-pentachlorobiphenyl (PCB126) on ER stress protein chaperon GRP78 and CCAAT-enhancer-binding protein homologous protein (CHOP) and intra-hepatic mediators such as microsomal triglyceride transfer protein (MTP), sterol regulatory element-binding protein 1c (SREBP1c), and peroxisome proliferator-activated receptor alpha (PPARα), as well as extra-hepatic factors such as non-esterified fatty acid (NEFA) and tumor necrosis factor alpha (TNFα). Hepatic GRP78 mRNA and protein levels, indicating the presence of ER stress, were significantly increased following a single PCB126 exposure in rats. Intra-hepatic mechanisms such as lipoprotein secretion pathway (i.e., MTP), lipogenesis de novo (i.e., SREBP1c), and oxidation (i.e., PPARα) were altered in PCB126-treated rats. In addition, a state of inflammation measured by higher TNFα plasma levels was present in contaminated rats. These data indicate that a single injection of PCB126-modulated expression of GRP78 associated with hepatic ER stress and systemic inflammation in rats.
authors: Institut de recherche de l'Hôpital Montfort, Institut du savoir Montfort, 713 Montreal Road, Pavillon E, Ottawa, Ontario, K1K 0T2, Canada. n.chapados@gmail.com.|Shcool of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada. n.chapados@gmail.com.
authors: Natalie A
authors: NA
authors: Chapados
authors: La Cité, Ottawa, Ontario, Canada.
authors: Marie-Pier
authors: MP
authors: Boucher
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010865:Pilot Projects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D005230:Fatty Acids, Nonesterified; C000717247:HSPA5 protein, human; C106092:microsomal triglyceride transfer protein; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl
keywords: Hepatic steatosis; Inflammation; PCB126; Rats; Unfolded protein response