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Effect of Isoquercitrin on Free Fatty Acid-Induced Lipid Accumulation in HepG2 Cells
Sou Hyun Kim1, Chawon Yun1, Doyoung Kwon2
1Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea.
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.
Insights
Isoquercitrin effectively reduces lipid accumulation in liver cells by activating AMP-activated protein kinase (AMPK) and inhibiting key lipid synthesis pathways, offering a potential treatment for nonalcoholic fatty liver disease (NAFLD).
Area of Science:
- Hepatology
- Molecular Biology
- Biochemistry
Background:
- Nonalcoholic fatty liver disease (NAFLD) is linked to liver metabolic disorders and oxidative stress, with limited treatment options.
- Developing effective strategies to combat NAFLD is a significant clinical challenge.
Purpose of the Study:
- To investigate the effect of isoquercitrin on free fatty acid (FFA)-induced lipid accumulation in HepG2 cells.
- To elucidate the molecular mechanisms underlying isoquercitrin's action on lipid metabolism.
Main Methods:
- HepG2 cells were treated with FFAs to induce lipid accumulation.
- Co-treatment with varying doses of isoquercitrin was used to assess its inhibitory potential.
- Expression of genes and proteins involved in lipid synthesis and AMPK signaling pathway were analyzed.
Main Results:
- Isoquercitrin significantly reduced intracellular lipid accumulation in FFA-treated HepG2 cells in a dose-dependent manner.
- Isoquercitrin suppressed endoplasmic reticulum (ER) stress and decreased the expression of lipid synthesis-related molecules.
- Isoquercitrin activated AMP-activated protein kinase (AMPK), leading to phosphorylation of acetyl-CoA carboxylase (ACC) and inhibition of sterol regulatory element-binding transcription factor 1 (SREBP-1)/fatty acid synthase (FAS) signaling.
Conclusions:
- Isoquercitrin demonstrates a therapeutic potential for NAFLD by regulating lipid metabolism.
- The mechanism involves the activation of the AMPK/ACC pathway and inhibition of the SREBP1/FAS pathway.
- Isoquercitrin may serve as a novel agent for managing NAFLD-associated metabolic dysfunction.
