| Popis: |
Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by fat accumulation and chronic inflammation in the liver. Although dynein light chain of 8 kDa (LC8) was identified previously as an inhibitor of nuclear factor kappa B (NF-κB), a key regulator of inflammation, its role in NASH remains unknown. In this study, we investigated whether LC8 can alleviate NASH using a mouse model of methionine and choline-deficient (MCD) diet–induced NASH and examined the underlying mechanism. LC8 transgenic (Tg) mice showed lower hepatic steatosis and less progression of NASH, including inflammation, oxidative stress, and hepatic fibrosis, compared to wild-type (WT) mice after consuming an MCD diet. The hepatic expression of lipogenic genes was lower, while that of lipolytic and mitochondrial genes was greater in LC8 Tg mice than WT mice, which might be associated with resistance of LC8 Tg mice to hepatic steatosis. Consumption of an MCD diet enhanced IκBα phosphorylation and subsequent p65 liberation from IκBα and nuclear translocation, resulting in induction of NF-κB targets, including pro-inflammatory cytokines and chemokines. However, these effects of MCD diet were reduced by LC8 overexpression. Taken together, these results suggest that LC8 alleviates MCD diet–induced NASH by inhibiting NF-κB through binding to IκBα to interfere with IκBα phosphorylation. |
