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

Abstract

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.

Plant miR8126-3p and miR8126-5p Decrease Lipid Accumulation through Modulation of Metabolic Genes in a Human Hepatocyte Model That Mimics Steatosis

“…This hypothesis relies on several facts: (1) the miRNA mechanism of action after mRNA interaction is mainly inhibitory [18], and (2) QKI and MAPKAPK2 inhibitions have been positively correlated with the prevention and/or counteraction of metabolic homeostasis disturbances including lipid alterations [34,37]. To validate this hypothesis, we used human hepatocytes (HepG2 cells) loaded with a mixture of FFAs (oleic and palmitic acids) as a model to mimic hepatic steatosis in vitro; this model was previously used in the study of plant bioactive compounds regulating lipid metabolism [42][43][44].…”

Doxorubicin Attenuates Free Fatty Acid-Induced Lipid Accumulation via Stimulation of p53 in HepG2 Cells

“…To measure cellular lipid deposition, Oil Red O staining (Sigma-Aldrich) was performed as previously described ( Kim et al ., 2023 ). To quantify Oil Red O content, dimethyl sulfoxide (DMSO) was added to each sample.…”

Unsaponifiable Matter from Wheat Bran Cultivated in Korea Inhibits Hepatic Lipogenesis by Activating AMPK Pathway

“…Our results indicate that USM from SKK and SMC reduces lipid accumulation by inhibiting the expression of the lipogenic proteins, including FAS and SREBP- To examine the effects of USM on lipid accumulation, HepG2 cells were treated with FFA and various concentrations of USM for 24 h. However, treatments with USM from SKK or SMC significantly inhibited FFA-induced fat accumulation (Figure 2A,B). In recent studies, the exposure of HepG2 cells to FFA increased lipid accumulation [38][39][40]. A previous study showed that wheat germ extract suppresses lipid accumulation in palmitic-acid-treated HepG2 cells [41].…”