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Toxicol Appl Pharmacol

Title:		Adipose tissue-liver crosstalk during pathologic changes caused by vinyl chloride metabolites in mice
Author(s):		Kaelin BR; McKenzie CM; Hempel KW; Lang AL; Arteel GE; Beier JI;
Address:		"Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States of America; Hepatobiology and Toxicology Program, University of Louisville, Louisville, KY 40292, United States of America. Electronic address: brka222@uky.edu. Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States of America; Hepatobiology and Toxicology Program, University of Louisville, Louisville, KY 40292, United States of America. Electronic address: cmmckenz@wakehealth.edu. Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States of America; Hepatobiology and Toxicology Program, University of Louisville, Louisville, KY 40292, United States of America. Electronic address: kwhemp01@louisville.edu. Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States of America; Hepatobiology and Toxicology Program, University of Louisville, Louisville, KY 40292, United States of America. Electronic address: all159@med.miami.edu. Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA 15213, United States of America; Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, United States of America. Electronic address: gearteel@pitt.edu. Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA 15213, United States of America; Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, United States of America. Electronic address: jibeier@pitt.edu"
Journal Title:		Toxicol Appl Pharmacol
Year:		2020
Volume:		20200520
Issue:
Page Number:		115068 -
DOI:		10.1016/j.taap.2020.115068
ISSN/ISBN:		1096-0333 (Electronic) 0041-008X (Print) 0041-008X (Linking)
Abstract:		"Volatile organic compounds (VOCs), such as vinyl chloride (VC), can be directly toxic at high concentrations. However, we have shown that 'nontoxic' exposures to VC and its metabolite chloroethanol (CE) enhances experimental non-alcoholic fatty liver disease (NAFLD), suggesting an unpredicted interaction. Importantly, VOC exposure has been identified as a potential risk factor for the development of obesity and its sequelae in humans. As there is a known axis between adipose and hepatic tissue in NAFLD, the impact of CE on white adipose tissue (WAT) inflammation and lipolysis was investigated. Mice were administered CE (or vehicle) once, after 10 weeks of being fed high-fat or low-fat diet (LFD). CE significantly enhanced hepatic steatosis and inflammation caused by HFD. HFD significantly increased the size of epididymal fat pads, which was enhanced by CE. The relative size of adipocyte lipid droplets increased by HFD + CE, which was also correlated with increased expression of lipid-associated proteins (e.g., PLINs). CE also enhanced HFD-induced indices of WAT inflammation, and ER stress. Hepatic-derived circulating FGF21, a major modulator of WAT lipolysis, which is hypothesized to thereby regulate hepatic steatosis, was significantly increased by CE in animals fed HFD. Taken together these data support the hypothesis that environmental toxicant exposure can exacerbate the severity of NAFLD/NASH, involving the liver-adipose axis in this process. Specifically, CE enhances local inflammation and alters lipid metabolism and WAT-mediated hepatic steatosis due to changes in WAT lipolysis"
Keywords:		"Adipocytes/drug effects/metabolism Adipose Tissue, White/*drug effects/*metabolism Animals Diet, High-Fat/adverse effects Inflammation/chemically induced/metabolism Lipid Metabolism/drug effects Lipids Liver/*drug effects/*metabolism Male Mice Mice, Inbre;"
Notes:		"MedlineKaelin, Brenna R McKenzie, Collin M Hempel, Karl W Lang, Anna L 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/ R21 ES031531/ES/NIEHS NIH HHS/ R01 AA021978/AA/NIAAA NIH HHS/ R01 AA028436/AA/NIAAA NIH HHS/ P30 DK120531/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2020/05/24 Toxicol Appl Pharmacol. 2020 Jul 15; 399:115068. doi: 10.1016/j.taap.2020.115068. Epub 2020 May 20"