Licochalcone D ameliorates lipid metabolism in hepatocytes by modulating lipogenesis and autophagy
European Journal of Pharmacology(2024)
Abstract
Metabolic dysfunction-associated fatty liver disease is a metabolic disease caused by abnormal lipid accumulation in the liver. Excessive lipid accumulation results in liver inflammation and fibrosis. Previous studies have demonstrated that the chalcone licochalcone D, which is isolated from Glycyrrhiza inflata Batal, has anti-tumor and anti-inflammatory effects. The present study explored whether licochalcone D can regulate lipid accumulation in fatty liver cells. FL83B hepatocytes were incubated with oleic acid to establish a fatty liver cell model, and then treated with licochalcone D to evaluate the molecular mechanisms underlying the regulation of lipid metabolism. In addition, male C57BL/6 mice were fed a methionine/choline-deficient diet to induce an animal model of metabolic dysfunction-associated steatohepatitis (MASH) and given 5 mg/kg licochalcone D by intraperitoneal injection. In cell experiments, licochalcone D significantly reduced lipid accumulation in fatty liver cells and reduced sterol regulatory element–binding protein 1c expression, blocking fatty acid synthase production. Licochalcone D increased adipose triglyceride lipase and carnitine palmitoyltransferase 1 expression, enhancing lipolysis and fatty acid β-oxidation, respectively. Licochalcone D also significantly increased SIRT-1 and AMPK phosphorylation, reducing acetyl-CoA carboxylase phosphorylation and inhibiting fatty acid synthesis. Licochalcone D also increased the fusion of autophagosomes and lysosomes to promote autophagy, reducing oil droplet accumulation in fatty liver cells. In the animal experiments, licochalcone D effectively reduced the number of lipid vacuoles and degree of fibrosis in liver tissue and inhibited liver inflammation. Thus, licochalcone D can improve MASH by reducing lipid accumulation, inhibiting inflammation, and increasing autophagy.
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Key words
Autophagy,Inflammation,Licochalcone D,Lipid Metabolism,MASH
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