Enhanced expression of pro-inflammatory mediators and liver X receptor-regulated lipogenic genes in nonalcoholic fatty liver disease and hepatitits C
Résumé
Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent chronic liver diseases worldwide. The metabolic factors associated with NAFLD are also determinants of liver disease progression in chronic hepatitis C virus (HCV) infection. It has been reported that, besides to induce hepatic fatty acid biosynthesis, liver X receptor (LXR) regulates a set of inflammatory genes. We aimed to evaluate the hepatic expression of LXRalpha and its lipogenic and inflammatory targets in forty-three patients with NAFLD, forty-four with chronic HCV infection, and in twenty-two with histologically normal liver. Real-time PCR and western blot were used to determine hepatic expression levels of LXRalpha and related lipogenic and inflammatory mediators in the study population. We found that LXRalpha gene and its lipogenic targets peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein-1c, sterol regulatory element binding protein-2 and fatty acid synthase were overexpressed in the liver of NAFLD and HCV patients who had steatosis. Moreover, up-regulation of inflammatory genes such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, osteopontin, inducible nitric oxide synthase, cyclooxygenase-2 and suppressors of cytokine signalling-3 was observed in NAFLD and HCV patients. Interestingly, TNF-alpha, IL-6 and osteopontin gene expression was lower in patients with steatohepatitis than in those with steatosis. In conclusion, hepatic expression of LXRalpha and its related lipogenic and inflammatory genes is abnormally increased in NAFLD and HCV patients with steatosis, suggesting a potential role of LXRalpha in the pathogenesis of hepatic steatosis in these chronic liver diseases.
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