Abstract: Objective To explore the alleviating effect of calcium / calmodulin-dependent protein kinase kinase β ( CaMKKβ) overexpression on high-fat induced non-alcoholic liver disease (NAFLD). Methods The SD rats were enrolled and divided into Control group, NAFLD group, NAFLD + LV group and NAFLD + LV-CaMKKβ group. The high-fat diet was applied to establish the NAFLD mouse models. Mice in the NAFLD + LV group and NAFLD + LV-CaMKKβ group were injected with lentivirus with empty vector and lentivirus with CaMKKβ-overexpression vector through the tail vein, respectively. The expression of CaMKKβ protein in liver tissues, the fatty vacuoles, the pathological tissues, the liver function indexes, the lipid accumulation, the oxidative damage markers, the AMPKα1 and Nrf2 phosphorylation and the positive expression of NF-κB P65 were detected and compared among the four groups. Results CaMKKβ overexpression led to a sharp contrast between the nucleus and cytoplasm in liver cells. The number of necrotic cells was significantly reduced. The lipid accumulation was significantly improved. The phosphorylations of Nrf2 and AMPKα1 in liver tissues were increased. The level of serum SOD was significantly increased (P < 0. 05). The levels of serum ALT, AST, TC, TG, MDA and LDH were significantly decreased, and the positive rate of NF-κB P65 cells was profoundly decreased as well (P< 0. 05). Conclusion Overexpression of CaMKKβ can alleviate high-fat induced NAFLD, which may be through inhibiting oxidative and inflammation response.

Key words: non-alcoholic liver disease, calmodulin-dependent protein kinase kinase β, oxidative stress, fatty liver