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Abstract
Nonalcoholic fatty liver disease (NAFLD) has become a global pandemic, imposing a significant socioeconomic burden. Hepatic steatosis is a key pathological event in NAFLD. However, there is still lack of effective drugs for NAFLD treatment. Liquiritin (LIQ), derived from licorice root, exhibits antioxidative and anti‐inflammatory properties, making it valuable in managing various conditions such as dermatological disorders, respiratory ailments, and gastritis. Here, we investigated the impact and underlying mechanisms of LIQ on hepatic steatosis in mouse primary hepatocytes (MPHs). Our study found that LIQ significantly decreased palmitic acid (PA)‐induced lipid accumulation in MPHs. Additionally, LIQ remarkably increased the mRNA expression of Cpt1a, PPARα, Ehhadh, Cyp4a10, and Acox1, suggesting that LIQ achieves its lipid‐lowering effect by regulating mitochondria‐mediated lipid β‐oxidation. Furthermore, the regulatory effect of LIQ on the mitochondrial oxidative phosphorylation (OXPHOS) process was confirmed by Seahorse analysis. Mechanistically, bioinformatics analysis predicted VEGFA as a crucial target mediating the beneficial effects of LIQ against PA‐induced lipid accumulation in MPHs. Notably, treatment with purified VEGFA protein partially counteracted the lipid‐lowering properties of LIQ. Additionally, our data showed that LIQ promoted VEGFA degradation through the ubiquitin–proteasome pathway. Therefore, our findings not only confirm the lipid‐lowering effects of LIQ in MPHs but also identify VEGFA as its potential target. These results highlight the therapeutic promise of LIQ in managing NAFLD and introduce VEGFA as a novel target for treating hepatic steatosis.
Published Version
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