Luteolin improves non-alcoholic fatty liver disease in db/db mice by inhibition of liver X receptor activation to down-regulate expression of sterol regulatory element binding protein 1c

Abstract

In this study, we report that daily administration of luteolin for 8 weeks improved hepatic steatosis by repressing hepatic TG accumulation and increasing glycogen storage. Luteolin inhibited hepatic de novo lipid synthesis by regulating the LXR-SREBP-1c signaling pathway, which is over-activated in the livers of db/db mice. Further in vitro studies revealed that luteolin can competitively bind to the ligand binding domain to suppress the LXR activation induced by an LXR agonist and high glucose, thereby decreasing TG accumulation in HepG2 cells and primary hepatocytes. Taken together, our results indicate that luteolin can abolish lipid accumulation induced by LXR-SREBP-1c activation both in vivo and in vitro, and may have potential as a therapeutic agent for treating NAFLD.

Keywords: Fatty acid; Liver X receptor; Luteolin; Non-alcoholic fatty liver disease; db/db mouse.