Liquiritigenin Ameliorates High-Fat Diet-Induced Hepatic Steatosis by Promoting Lipid Droplet Catabolism via PLIN2-ATGL Regulation.

Abstract

Metabolic-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD) has caused a significant health burden. Glycyrrhiza uralensis Fisch. is a traditional Chinese medicinal herb used to prevent and treat numerous diseases. Liquiritigenin (LQ), a flavonoid isolated from Glycyrrhiza uralensis Fisch., has shown potential benefits in regulating lipid metabolism. This study aimed to analyze whether LQ was involved in ameliorating hepatic steatosis and elucidate the specific molecular mechanisms. A high-fat diet (HFD) model of male C57BL/6J mice was established to evaluate the effects of LQ on regulating hepatic steatosis. The potential molecular mechanisms of LQ on promoting lipid droplet catabolism were assessed in vitro using HepG2 cells treated with palmitic acid (PA) and/or LQ. The impact of the PLIN2-ATGL signaling in lipid droplet catabolism was elucidated by treating HepG2 cells with NG-497 (an ATGL inhibitor), the inhibitor of ATGL, and by constructing Plin2-overexpressed HepG2 cell lines. Both in vivo and in vitro experiments demonstrated that LQ alleviated excessive lipid accumulation, enhanced lipolysis and lipophagy, down-regulated PLIN2 expression and up-regulated CGI-58 expression. Further, inhibiting lipolysis with NG-497, the inhibitor of ATGL, attenuated the effects of LQ on increasing the phosphorylation of HSL and promoting lipophagy. The results also showed that transfecting HepG2 cells with a Plin2-overexpressing vector reduced the effects of LQ on up-regulating the expression of CGI-58, as well as proteins related to lipolysis and lipophagy. LQ promoted lipid droplet catabolism through the activation of lipolysis and lipophagy by regulating PLIN2-ATGL signaling, which provided evidence for developing LQ as a functional compound in food for ameliorating hepatic steatosis.