title: Fatty liver and anti-oxidant enzyme activities along with peroxisome proliferator-activated receptors γ and α expressions in the liver of Wilson's disease.
abstract: BACKGROUND
  The mechanisms of liver damage and steatosis in Wilson's disease (WD) presenting accumulation of copper generating oxidants remain unclear. Recent studies have shown that peroxisome proliferator-activated receptors (PPARs), in particular PPARs α and γ, regulate fat content of the liver together with the anti-oxidant and anti-inflammation systems. However, such PPARs have never been studied in WD.
  
  
  METHODS
  We examined PPARs along with the liver damage and steatosis of WD using liver specimens from affected patients exhibiting mild liver damage (group I, n = 5), moderate or greater liver damage (group II, n = 10) and fulminant hepatic failure (group III, n = 5), and from asymptomatic carriers (group H, n = 4).
  
  
  RESULTS
  PPAR α expression was increased over the control levels in groups H and I but was decreased in groups II and III in parallel with the progression of liver damage (group H = I>II>III). PPAR γ expression was inversely increased (group H<I<II<III). Mn-dependent superoxide dismutase (Mn-SOD), CuZn-SOD, and catalase activities were decreased in the affected three groups, and were increased in group H. Among group II exhibiting substantial inter-individual variances in parameters, the severity of steatosis showed a significant positive correlation with PPAR γ expression (p<0.001) but not PPAR α expression. CuZn-SOD activity was positively correlated with PPARα expression (p<0.05) but not PPAR γ expression.
  
  
  CONCLUSIONS
  These results suggest that changes of PPARs γ and α are associated with the steatosis and the impairment of anti-oxidant system in the liver of WD.
authors.affiliation: Department of Pediatrics, Takarazuka City Hospital, 4-5-1 Kohama-cho, Takarazuka 665-0827, Japan. nagasa-hirono@k2.dion.ne.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Nagasaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Miida
authors.forename: Ayano
authors.initials: A
authors.lastname: Inui
authors.forename: Ikuo
authors.initials: I
authors.lastname: Inoue
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tsukahara
authors.forename: Haruki
authors.initials: H
authors.lastname: Komatsu
authors.forename: Eitaro
authors.initials: E
authors.lastname: Hiejima
authors.forename: Tomoo
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Yorifuji
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hiranao
authors.forename: Hideaki
authors.initials: H
authors.lastname: Okajima
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Inomata
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D058070:Asymptomatic Diseases; D002374:Catalase / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006527:Hepatolenticular Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D007527:Isoenzymes; D047493:PPAR alpha; D047495:PPAR gamma; D003300:Copper; D002374:Catalase; D013482:Superoxide Dismutase; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases