Licochalcone A ameliorates lipid accumulation in metabolic dysfunction-associated steatotic liver disease via upregulating PPARα/CPT1α.

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent hepatic disorder with high morbidity and mortality. Licochalcone A (LiA) exhibits significant therapeutic efficacy in obesity through diverse pharmacological mechanisms. This study aimed to explore the efficacy and underlying mechanism of LiA in attenuating MASLD, which requires further investigation.

Methods: Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks to establish a MASLD mouse model. The lipid level and liver function of mice were evaluated by the levels of TG, TC, ALT, and AST. H&E staining and Oil Red O staining were used to evaluate the pathological changes and lipid deposits in the liver. Lipid metabolism and PPARα/CPT1α signaling pathway-related genes were detected.

Results: LiA effectively reduced weight and improved glucose tolerance and insulin resistance in MASLD mice. LiA treatment significantly reduced lipid accumulation in HFD-induced mice. In addition, bioinformatics analysis, molecular docking, and cellular thermal shift assays further indicated that LiA alleviated MASLD by upregulating PPARα. Furthermore, the protective effect of LiA on lipid accumulation and hepatic steatosis was abolished by PPARα inhibitor (GW7461) pretreatment in MASLD mice.

Conclusion: This study demonstrated that LiA ameliorates the lipid metabolism disorder in MASLD mice by upregulating the PPARα/CPT1α signaling pathway.