Adipose tissue-liver crosstalk during pathologic changes caused by vinyl chloride metabolites in mice

Brenna R. Kaelin, Collin M. McKenzie, Karl W. Hempel, Anna L. Lang, Gavin E. Arteel, Juliane I. Beier

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number115068
JournalToxicology and Applied Pharmacology
Volume399
DOIs
StatePublished - Jul 15 2020
Externally publishedYes

Keywords

  • Hepatotoxicity
  • Metabolic syndrome
  • Plastic
  • PVC
  • Saturated fat
  • TASH

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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