Department of Internal Medicine, General Hospital Oberndorf, Oberndorf, Austria.
Am J Gastroenterol. 2010 Sep;105(9):1978-85. doi: 10.1038/ajg.2010.170. Epub 2010 Apr 20.
Copper has a role in antioxidant defense, lipid peroxidation, and mitochondrial function, and copper deficiency has been linked to atherogenic dyslipidemia. We aimed to investigate the potential role of copper availability in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).
Patients with NAFLD (n=124) were compared to patients with chronic hepatitis C (n=50), hemochromatosis (n=35), alcoholic liver disease (n=13), autoimmune hepatitis (n=11), and control subjects (n=27). We determined liver and serum copper concentrations with correlation to clinical, histological, and biochemical parameters in humans. The effect of dietary copper restriction on liver histology and intermediary metabolism in rats was investigated.
Hepatic copper concentrations in patients with NAFLD were lower than in control subjects (17.9+/-8.4 vs. 31.4+/-8.2 microg/g; P<0.001) and in patients with other liver diseases (P<0.05 for all liver diseases). In patients with NAFLD, lower liver copper was correlated with more pronounced hepatic steatosis (R=-0.248; P=0.010), fasting glucose (R=-0.245; P=0.008), and components of the metabolic syndrome (MetS; R=0.363; P<0.001). Patients with nonalcoholic steatohepatitis (NASH; n=31) had lower hepatic copper concentrations than those with simple steatosis (n=93; P=0.038). Restriction of dietary copper in rats induced hepatic steatosis and insulin resistance (IR).
Reduced hepatic copper concentrations are found in human NAFLD and are associated with more pronounced hepatic steatosis, NASH, and components of the MetS. The development of hepatic steatosis and IR in response to dietary copper restriction in rats suggests that copper availability may be involved in the development of NAFLD.
铜在抗氧化防御、脂质过氧化和线粒体功能中发挥作用，铜缺乏与动脉粥样硬化性血脂异常有关。我们旨在研究铜供应在非酒精性脂肪性肝病（NAFLD）发病机制中的潜在作用。
将 124 例 NAFLD 患者与慢性丙型肝炎（n=50）、血色病（n=35）、酒精性肝病（n=13）、自身免疫性肝炎（n=11）和对照组（n=27）进行比较。我们用人的临床、组织学和生化参数来确定肝和血清铜浓度，并进行相关性分析。研究饮食铜限制对大鼠肝组织学和中间代谢的影响。
NAFLD 患者的肝铜浓度低于对照组（17.9+/-8.4 与 31.4+/-8.2μg/g；P<0.001）和其他肝病患者（所有肝病患者均 P<0.05）。在 NAFLD 患者中，较低的肝铜与更明显的肝脂肪变性（R=-0.248；P=0.010）、空腹血糖（R=-0.245；P=0.008）和代谢综合征（MetS）的成分（R=0.363；P<0.001）相关。非酒精性脂肪性肝炎（NASH；n=31）患者的肝铜浓度低于单纯性脂肪变性（n=93；P=0.038）。限制大鼠饮食铜会引起肝脂肪变性和胰岛素抵抗（IR）。
在人类 NAFLD 中发现肝铜浓度降低，与更明显的肝脂肪变性、NASH 和 MetS 成分相关。饮食铜限制大鼠发生肝脂肪变性和 IR，提示铜的可利用性可能参与了 NAFLD 的发生。
