Conclusions
These results provide evidence for a novel role of S100A11 that contributes to hepatic steatosis, suggesting that targeting S100A11 may be an alternative approach for the treatment of NAFLD.
Methods
Immunohistochemical staining was performed using human NAFLD and control biopsy specimens. Serum level of S100A11 were analyzed by Elisa assays. The S100A11 over-expressed/ knocked-down model was established in vitro or in vivo. The expression levels of genes related to lipid metabolism in liver tissue were performed by quantitative PCR and western blotting. Hepatic lipid accumulation was determined by biochemical measurements and histochemistry.
Results
We showed that the concentration of serum S100A11 was significantly elevated in NAFLD patients, and expression of S100A11 was remarkedly increased in the livers of NAFLD patients and mouse models. Overexpression of S100A11 in vivo markedly increased liver steatosis, body weight, and serum aspartate aminotransaminase (AST) levels. Mechanistically, our results demonstrated that S100A11 acted as a positive regulator of AKT/mTOR signaling to induce lipid synthesis and aggravate lipid deposition. Conclusions: These results provide evidence for a novel role of S100A11 that contributes to hepatic steatosis, suggesting that targeting S100A11 may be an alternative approach for the treatment of NAFLD.