Jnk1 but not jnk2 promotes the development of steatohepatitis in mice†

• DOI: 10.1002/hep.20999
• Publication Date: 2005-12-22T22:17:17Z
• Authors: Jörn M. Schattenberg; Rajat Singh; Yongjun Wang; Jay H. Lefkowitch; Raina M. Rigoli; Philipp E. Scherer; Mark J. Czaja
• Keywords: Steatohepatitis; Steatosis

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and varying degrees of necroinflammation. Although chronic oxidative stress, inflammatory cytokines, insulin resistance have been implicated in the pathogenesis NAFLD, mechanisms that underlie initiation progression this remain unknown. c-Jun N-terminal kinase (JNK) activated oxidants cytokines regulates hepatocellular injury resistance, suggesting may mediate development steatohepatitis. The presence function JNK activation were therefore examined murine methionine- choline-deficient (MCD) diet model Activation JNK, c-Jun, AP-1 signaling occurred parallel with steatohepatitis MCD diet-fed mice. Investigations jnk1 jnk2 knockout mice demonstrated jnk1, but not jnk2, was critical for diet-induced activation. promoted as null had significantly reduced levels triglyceride accumulation, inflammation, lipid peroxidation, injury, apoptosis compared wild-type -/- Ablation led to an increase serum adiponectin no effect on tumor necrosis factor-alpha. In conclusion, JNK1 responsible promotes model. These findings also provide additional support mechanistic involvement overactivation conditions associated metabolic syndrome.