title: Putative mechanisms of environmental chemical-induced steatosis.
abstract: Liver disease is a major health issue characterized by several pathological changes, with steatosis (fatty liver) representing a common initial step in its pathogenesis. Steatosis is of critical importance because prevention of fatty liver can obviate downstream pathologies of liver disease (eg, fibrosis). Recent studies have shown a strong correlation between chemical exposure and steatosis. The work described here identifies chemicals on the US Environmental Protection Agency's Integrated Risk Information System (IRIS) that induce steatosis and investigates putative mechanisms by which these chemicals may contribute to this pathological condition. Mitochondrial impairment, insulin resistance, impaired hepatic lipid secretion, and enhanced cytokine production were identified as potential mechanisms that could contribute to steatosis. Taken together, this work is significant because it identifies multiple mechanisms by which environmental chemicals may cause fatty liver and expands our knowledge of the possible role of environmental chemical exposure in the induction and progression of liver disease.
authors.affiliation: US Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment, Cincinnati, OH 45268, USA. kaiser.jonathan-phillip@epa.gov
authors.forename: J Phillip
authors.initials: JP
authors.lastname: Kaiser
authors.forename: John C
authors.initials: JC
authors.lastname: Lipscomb
authors.forename: Scott C
authors.initials: SC
authors.lastname: Wesselkamper
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000493:pharmacokinetics / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D016208:Databases, Factual; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005234:Fatty Liver / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D018570:Risk Assessment; D014752:Vinyl Chloride / Q000493:pharmacokinetics / Q000633:toxicity; D015262:Xenobiotics / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated; D015262:Xenobiotics; D002251:Carbon Tetrachloride; D014752:Vinyl Chloride