Kaempferol Inhibits Lipid Accumulation in HepG2 Cells through AMPK-Mediated Autophagy.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with metabolic syndrome. Currently, it is considered as a global health concern. Kaempferol (a flavonoid) exhibits extensive pharmacological properties, including anti-inflammatory, antioxidant, anticancer, and neuroprotective effects. In the present study, we investigated the effects of kaempferol on free fatty acid (FFA)-induced lipid accumulation in HepG2 cells. To establish an in vitro model of MASLD, we treated the human hepatocellular carcinoma cell line HepG2 with FFAs. Subsequently, we performed Western blot analysis to analyze the expression levels of essential proteins associated with lipogenesis and autophagy. Vital lipogenesis-related proteins (e.g., acetyl-CoA carboxylase, fatty acid synthase, sterol regulatory element-binding protein-1c, CCAAT/enhancer-binding protein alpha, and peroxisome proliferator-activated receptor gamma) were downregulated by kaempferol treatment. Concurrently, the expression of proteins involved in fatty acid oxidation (e.g., carnitine palmitoyltransferase 1 and peroxisome proliferator-activated receptor alpha) was upregulated. These changes indicate that kaempferol promotes a shift toward enhanced fatty acid oxidation and reduced lipogenesis, thereby mitigating lipid accumulation in liver cells. Our findings suggest that kaempferol exerts a protective effect against MASLD by modulating lipid metabolism via autophagy activation.