芳香烃受体
脂肪变性
多氯联苯
酒精性肝病
脂肪肝
污染物
内科学
非酒精性脂肪肝
内分泌学
肝病
肝功能
白蛋白
化学
生理学
医学
肝硬化
生物化学
环境化学
疾病
基因
有机化学
转录因子
作者
Tyler C. Gripshover,Banrida Wahlang,Kimberly Z. Head,Jamie L. Young,Jianzhu Luo,Muhammad T. Mustafa,Irina Kirpich,Matthew C. Cave
摘要
Abstract Background The prevalence of alcohol‐associated liver disease (ALD), a subtype of fatty liver disease (FLD), continues to rise. ALD is a major cause of preventable death. Polychlorinated biphenyl (PCB) 126 is an environmentally relevant, dioxin‐like pollutant whose negative metabolic effects have been well documented. In human and animal studies, PCB has been associated with the severity of nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated whether exposures to environmental toxicants can worsen ALD. Thus, the objective of the current study was to develop an alcohol‐plus‐toxicant model to study how an environmental pollutant, PCB 126, impacts rodent ALD pathology. Methods Briefly, male C57BL/6J mice were exposed to 0.2 mg/kg PCB 126 or corn oil vehicle four days prior to ethanol feeding using the chronic‐binge (10‐plus‐one) model. Results Concentrations of macromolecules, including hepatic lipids, carbohydrates, and protein (albumin) were impacted. Exposure to PCB 126 exacerbated hepatic steatosis and hepatomegaly in mice exposed to the chemical and fed an ethanol diet. Gene expression and the analysis of blood chemistry showed a potential net increase and retention of hepatic lipids and reductions in lipid oxidation and clearance capabilities. Depletion of glycogen and glucose was evident, which contributes to disease progression by generating systemic malnutrition. Granulocytic immune infiltrates were present but driven solely by ethanol feeding. Hepatic albumin gene expression and plasma levels were decreased by ~50% indicating a potential compromise of liver function. Finally, gene expression analyses indicated that the aryl hydrocarbon receptor and constitutive androstane receptor were activated by PCB 126 and ethanol, respectively. Conclusions Various environmental toxicants are known to modify or enhance FLD in high‐fat diet models. Findings from the present study suggest that they interact with other lifestyle factors such as alcohol consumption to reprogram intermediary metabolism resulting in exacerbated ethanol‐associated systemic malnutrition in ALD.
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