Abstract
Previous findings supported that fetuin B, a new hepatokine, may be involved in the development of hepatic steatosis, but the mechanism is still unknown. This study aims to investigate the role of fetuin B in hepatic steatosis in C57BL/6 mice and HepG2 cells. 1) We found that the administration of recombinant fetuin B aggravated hepatic lipid accumulation caused by free fatty acids (FFAs) or high fat diet, in vivo and in vitro. It lowered the phosphorylated AMPK levels and activated the LXR-SREBP1c pathway, accompanied by the downregulation of fatty acid oxidation and upregulation of lipogenesis. Furthermore, in HepG2 cells exposed to recombinant fetuin B and FFAs, the AMPK agonist depressed the LXR-SREBP1c pathway and alleviated lipid accumulation. The knockdown of LXR protected against steatosis but failed to change phosphorylated AMPK. 2) The knockdown of fetuin B by siRNA or shRNA alleviated lipid accumulation, in vivo and in vitro. It enhanced phosphorylated AMPK and depressed the LXR-SREBP1c pathway, accompanied by upregulation of fatty acid oxidation and downregulation of lipogenesis. Moreover, in HepG2 cells exposed to fetuin B siRNA and FFAs, LXR agonist aggravated lipid accumulation but failed to influence AMPK. This study indicated that fetuin B aggravated LXR-mediated hepatic steatosis through AMPK. It might offer new insights into clinical management and biomarker research on fatty liver.