| Title: | Vinyl Chloride and High-Fat Diet as a Model of Environment and Obesity Interaction |
| Author(s): | Lang AL; Goldsmith WT; Schnegelberger RD; Arteel GE; Beier JI; |
| Address: | "Department of Pharmacology and Toxicology, University of Louisville; Hepatobiology and Toxicology Program, University of Louisville. Department of Physiology and Pharmacology, West Virginia University; Center for Inhalation Toxicology, West Virginia University. Department of Pharmacology and Chemical Biology, University of Pittsburgh; Pittsburgh Liver Research Center, University of Pittsburgh. Pittsburgh Liver Research Center, University of Pittsburgh; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh. Pittsburgh Liver Research Center, University of Pittsburgh; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh; jibeier@pitt.edu" |
| ISSN/ISBN: | 1940-087X (Electronic) 1940-087X (Linking) |
| Abstract: | "Vinyl chloride (VC), an abundant environmental contaminant, causes steatohepatitis at high levels, but is considered safe at lower levels. Although several studies have investigated the role of VC as a direct hepatotoxicant, the concept that VC modifies sensitivity of the liver to other factors, such as nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet (HFD) is novel. This protocol describes an exposure paradigm to evaluate the effects of chronic, low-level exposure to VC. Mice are acclimated to low-fat or high-fat diet one week prior to the beginning of the inhalation exposure and remain on these diets throughout the experiment. Mice are exposed to VC (sub-OSHA level: <1 ppm) or room air in inhalation chambers for 6 hours/day, 5 days/week, for up to 12 weeks. Animals are monitored weekly for body weight gain and food consumption. This model of VC exposure causes no overt liver injury with VC inhalation alone. However, the combination of VC and HFD significantly enhances liver disease. A technical advantage of this co-exposure model is the whole-body exposure, without restraint. Moreover, the conditions more closely resemble a very common human situation of a combined exposure to VC with underlying nonalcoholic fatty liver disease and therefore support the novel hypothesis that VC is an environmental risk factor for the development of liver damage as a complication of obesity (i.e., NAFLD). This work challenges the paradigm that the current exposure limits of VC (occupational and environmental) are safe. The use of this model can shed new light and concern on the risks of VC exposure. This model of toxicant-induced liver injury can be used for other volatile organic compounds and to study other interactions that may impact the liver and other organ systems" |
| Keywords: | "Administration, Inhalation Animals Diet, High-Fat/*adverse effects *Environmental Exposure Humans Liver/drug effects/injuries/pathology Liver Diseases/etiology Mice, Inbred C57BL *Models, Biological Obesity/*etiology Vinyl Chloride/*toxicity;Animals;" |
| Notes: | "MedlineLang, Anna L Goldsmith, William T Schnegelberger, Regina D Arteel, Gavin E Beier, Juliane I eng R03 DK107912/DK/NIDDK NIH HHS/ P20 GM113226/GM/NIGMS NIH HHS/ K01 DK096042/DK/NIDDK NIH HHS/ P50 AA024337/AA/NIAAA NIH HHS/ P30 DK120531/DK/NIDDK NIH HHS/ R21 ES031531/ES/NIEHS NIH HHS/ R01 AA021978/AA/NIAAA NIH HHS/ Research Support, N.I.H., Extramural Video-Audio Media 2020/01/28 J Vis Exp. 2020 Jan 12; (155):10.3791/60351. doi: 10.3791/60351" |
