Adipose tissue-liver crosstalk during pathologic changes caused by vinyl chloride metabolites in mice
Autor: | Collin M. McKenzie, Karl W. Hempel, Brenna R. Kaelin, Juliane I. Beier, Gavin E. Arteel, Anna L. Lang |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty FGF21 Saturated fat Adipose Tissue White Vinyl Chloride Adipose tissue White adipose tissue Toxicology Diet High-Fat Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Non-alcoholic Fatty Liver Disease Adipocyte Internal medicine medicine Adipocytes Lipolysis Animals Obesity Pharmacology Inflammation Fatty liver nutritional and metabolic diseases food and beverages medicine.disease Lipid Metabolism Lipids Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry Liver 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) Steatosis |
Zdroj: | Toxicol Appl Pharmacol |
Popis: | 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. |
Databáze: | OpenAIRE |
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