Nonalcoholic fatty liver disease (
NAFLD) is a clinicopathological syndrome characterized by excessive deposition of
fatty acids in the liver. Further deterioration leads to
nonalcoholic steatohepatitis,
cirrhosis, and
hepatocellular carcinoma, creating a heavy burden on human health and the social economy. Currently, there are no effective and specific drugs for the treatment of
NAFLD. Therefore, it is important to further investigate the pathogenesis of
NAFLD and explore effective therapeutic targets for the prevention and treatment of the disease. Six-transmembrane epithelial
antigen of prostate 3 (STEAP3), a STEAP family
protein, is a metalloreductase. Studies have shown that it can participate in the regulation of liver
ischemia-reperfusion injury,
hepatocellular carcinoma, myocardial
hypertrophy, and other diseases. In this study, we found that the expression of STEAP3 is upregulated in
NAFLD. Deletion of STEAP3 inhibits the development of
NAFLD in vivo and in vitro, whereas its overexpression promotes
palmitic acid/
oleic acid stimulation-induced
lipid deposition in hepatocytes. Mechanistically, it interacts with
transforming growth factor beta-activated kinase 1 (TAK1) to regulate the progression of
NAFLD by promoting TAK1 phosphorylation and activating the TAK1-c-Jun N-terminal
kinase/p38 signaling pathway. Taken together, our results provide further insight into the involvement of STEAP3 in liver pathology.