Effect of Isoquercitrin on Free Fatty Acid-Induced Lipid Accumulation in HepG2 Cells

Liver metabolic disorders and oxidative stress are crucial factors in the development of nonalcoholic fatty liver disease (NAFLD); however, treatment strategies to combat NAFLD remain poorly established, presenting an important challenge that needs to be addressed. Herein, we aimed to examine the effect of isoquercitrin on lipid accumulation induced by exogenous free fatty acids (FFA) using HepG2 cells and elucidate the underlying molecular mechanism. The cells were exposed to 0.5 mM FFA to induce intracellular lipid accumulation, followed by co-treatment with isoquercitrin to confirm the potential inhibitory effect on FFA-induced lipid production. HepG2 cells exposed to FFA alone exhibited intracellular lipid accumulation, compromised endoplasmic reticulum (ER) stress, and enhanced expression of proteins and genes involved in lipid synthesis; however, co-treatment with isoquercitrin decreased the expression of these molecules in a dose-dependent manner. Furthermore, isoquercitrin could activate AMP-activated protein kinase (AMPK), a key regulatory protein of hepatic fatty acid oxidation, suppressing new lipid production by phosphorylating acetyl-CoA carboxylase (ACC) and inhibiting sterol regulatory element-binding transcription factor 1 (SREBP-1)/fatty acid synthase (FAS) signals. Overall, these findings suggest that isoquercitrin can be employed as a therapeutic agent to improve NAFLD via the regulation of lipid metabolism by targeting the AMPK/ACC and SREBP1/FAS pathways.

Automated summary

Liver metabolic disorders and oxidative stress play important roles in the development of NAFLD and there is currently a lack of established treatment strategies for this disease. This study investigates the impact of isoquercitrin on lipid accumulation induced by exogenous free fatty acids (FFA) in HepG2 cells and explores the underlying mechanisms. The results show that isoquercitrin can inhibit FFA-induced lipid production by suppressing endoplasmic reticulum stress and reducing the expression of proteins and genes involved in lipid synthesis. Furthermore, isoquercitrin activates AMPK, a key regulator of hepatic fatty acid oxidation, to suppress new lipid production. Overall, these findings suggest that isoquercitrin may be a potential therapeutic agent for improving NAFLD by targeting lipid metabolism through the AMPK/ACC and SREBP1/FAS pathways.