title: The effects of PCB126 on intra-hepatic mechanisms associated with non alcoholic fatty liver disease.
abstract: BACKGROUND
  Non alcoholic fatty liver disease (NAFLD) results from alteration in lipid synthesis and elimination mechanisms such as very-low density lipoprotein (VLDL) production and de novo lipogenesis. Persistent organic pollutants (POPs) are chemicals that were mostly used historically as pesticides, solvents, flame retardant, and other applications. Among POPs, polychlorinated biphenyls (PCB) have been recognized to be of environmental and potential toxicologic concerns. Specifically, PCB126 could act as endocrine disruptors and has recently been associated with hepatic fat accumulation. The purpose of the study was to investigate the effects of PCB126 on the molecular development of NAFLD using hepatocyte and rat models.
  
  
  METHODS
  Hepatocytes were exposed to PCB 126 for 72 h and lipid accumulation in cells was quantified by Oil-Red-O. Rats were injected with a single dose of PCB126 or vehicle. Seven days later, liver triglycerides (TAG) content was measured along with protein quantification of hepatic microsomal triglyceride transfer protein (MTP), sterol regulatory element-binding protein 1c (SREBP1c) and diacylglycerol O-acyltransferase 2 (DGAT-2).
  
  
  RESULTS
  Exposure to PCB126 resulted in significant increases of lipid accumulation in hepatocytes (38 %, P <0.05) and hepatic TAG concentrations (64 %, P <0.001) in rats compared to respective control groups. Rats with fatty livers depicted lower MTP (40 %, P <0.02), higher SREBP1c (27 %, P < 0.05) and DGAT-2 (120 %, P < 0.02) protein content levels compared to Placebo group in rats.
  
  
  CONCLUSIONS
  It seems that exposure to PCB126 has an important emerging role in the pathophysiology of NAFLD by 1) altering elimination mechanisms such as VLDL synthesis and secretion, through MTP; and 2) increasing hepatic TAG synthesis mechanisms through DGAT 2 and SREBP1c.
authors.affiliation: La Cite, Ottawa, ON Canada.
authors.forename: Marie-Pier
authors.initials: MP
authors.lastname: Boucher
authors.affiliation: La Cite, Ottawa, ON Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lefebvre
authors.affiliation: Institut de recherche de l`Hôpital Montfort, Hôpital Montfort, 713 Montreal Road, Ottawa, ON K1K 0T2 Canada ; School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON Canada.
authors.forename: Natalie Ann
authors.initials: NA
authors.lastname: Chapados
keywords: Environmental contaminants; Liver; Rats; Steatosis