title: A role for low hepatic copper concentrations in nonalcoholic Fatty liver disease.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, General Hospital Oberndorf, Oberndorf, Austria.
authors.forename: Elmar
authors.initials: E
authors.lastname: Aigner
authors.forename: Michael
authors.initials: M
authors.lastname: Strasser
authors.forename: Heike
authors.initials: H
authors.lastname: Haufe
authors.forename: Thomas
authors.initials: T
authors.lastname: Sonnweber
authors.forename: Florian
authors.initials: F
authors.lastname: Hohla
authors.forename: Andreas
authors.initials: A
authors.lastname: Stadlmayr
authors.forename: Marc
authors.initials: M
authors.lastname: Solioz
authors.forename: Herbert
authors.initials: H
authors.lastname: Tilg
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Patsch
authors.forename: Guenter
authors.initials: G
authors.lastname: Weiss
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
mesh_terms: D000328:Adult; D000818:Animals; D003300:Copper / Q000032:analysis* / Q000097:blood; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006432:Hemochromatosis / Q000378:metabolism / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000378:metabolism / Q000473:pathology; D019693:Hepatitis, Autoimmune / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007328:Insulin / Q000097:blood; D008099:Liver / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
chemical_list: D007328:Insulin; D003300:Copper