Title: Adipose tissue-liver crosstalk during pathologic changes caused by vinyl chloride metabolites in mice.
Authors: Kaelin, Brenna R; McKenzie, Collin M; Hempel, Karl W; Lang, Anna L; Arteel, Gavin E; Beier, Juliane I
Published In Toxicol Appl Pharmacol, (2020 07 15)
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.
PubMed ID: 32445754
MeSH Terms: Adipocytes/drug effects; Adipocytes/metabolism; Adipose Tissue, White/drug effects*; Adipose Tissue, White/metabolism*; Animals; Diet, High-Fat/adverse effects; Inflammation/chemically induced; Inflammation/metabolism; Lipid Metabolism/drug effects; Lipids; Liver/drug effects*; Liver/metabolism*; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease/metabolism; Obesity/chemically induced; Obesity/metabolism; Vinyl Chloride/toxicity*