Kurzfassung

The methionine and choline-deficient (MCD) diet induces steatohepatitis characterized by intense steatosis and lipidperoxidation, inflammation and intrahepatic insulin resistance. This allows examining intrahepatic changes related to insulin signaling pathway abnormalities and lipid accumulation. On the other hand this model does not exhibit extrahepatic insulin resistance and the contribution of fat-tissue derived mediators and cytokines or impaired glucose uptake in muscle tissue in the...The methionine and choline-deficient (MCD) diet induces steatohepatitis characterized by intense steatosis and lipidperoxidation, inflammation and intrahepatic insulin resistance. This allows examining intrahepatic changes related to insulin signaling pathway abnormalities and lipid accumulation. On the other hand this model does not exhibit extrahepatic insulin resistance and the contribution of fat-tissue derived mediators and cytokines or impaired glucose uptake in muscle tissue in the pathogenesis of NAFLD can not be adequately examined using the MCD diet.
Increased signaling through death receptors has been implicated in liver injury in patients with NAFLD and increased expression of CD95/Fas can be observed (1). These findings translate into the leptin-deficient ob/ob mouse model of NAFLD as these animals exhibit increased sensitivity towards CD95-induced liver injury. Additional evidence implying death receptor signaling pathways in the pathogenesis of NAFLD comes from animals studies examining inhibition of the death receptor adapter protein Fas-asscoiated death domain (FADD) through expression of a dominant negative protein (dnFADD). These animals exhibited reduced liver injury when fed the MCD diet. Similar results were observed in mice with congenital deletion of NEMO/IKKgamma which develop steatohepatitis over time which is blocked through deletion of FADD.
» weiterlesen» einklappen