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. Conclusion: 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.
- Peroxisome proliferator-activated receptors
- Superoxide dismutase
- Wilson's disease
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Molecular Biology