Articles
Vol. 69 No. 4 (2025)
https://doi.org/10.4081/ejh.2025.4309

Folic acid promotes autophagy to relieve metabolism-associated fatty liver disease by regulating NRF2

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Published: 3 November 2025
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Data Availability Statement

The data analyzed during this study are available from the corresponding author upon reasonable request.

metabolism-related fatty liver disease, folic acid, autophagy, NRF2, lipid accumulation

Authors

Yu Wen
Department of Emergency Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Juan Luo
Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Chunjing Shi
Department of General Tuberculosis, The Third People's Hospital of Kunming, Yunnan, China.
Jie Wu
wujie5@kmmu.edu.cn
Department of Emergency Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Metabolism-associated fatty liver disease (MAFLD) is a liver disease characterized by hepatic steatosis and excessive accumulation of lipids, with a high global incidence, especially in populations with obesity, diabetes and metabolic syndrome (MetS). As an important B vitamin, folate (FA) is stored mainly in the liver where it regulates oxidative stress, chronic inflammation and lipid metabolism. However, its regulatory role and mechanism of action in MAFLD are still poorly understood. Therefore, this study was conducted to investigate the regulatory effect of FA on MAFLD. The MAFLD rat model was induced by a high-fat diet (HFD), and HepG2 cells were treated with 0.3 mM palmitic acid (PA) for 24 h to establish a cell model. The expression of relevant genes and proteins was detected by RT-qPCR and Western blotting. Injury to HepG2 cells and rat liver tissues was evaluated via hematoxylin and eosin staining, Oil red O staining, ELISA and CCK-8 assay. FA treatment inhibited body weight gain in rats and reduced the levels of liver injury indicators (aspartate and alanine aminotransferase, and Alkaline phosphatase), blood lipids (total cholesterol, triglycerides and free fatty acids) and inflammatory cytokines (TNF-α, IL-6, and IL-1β), reducing lipid accumulation and pathological damage in the liver and ultimately alleviating the progression of MAFLD. Moreover, FA treatment promoted the expression of the autophagy-related protein LC3 II/I, inhibited the expression of p62, and increased the formation of autophagosomes, thereby alleviating PA-induced damage to HepG2 cells. Furthermore, NRF2 expression is downregulated in MAFLD and can be upregulated by FA treatment. Further examination revealed that knocking down NRF2 could partially attenuate the inhibitory effect of FA on PA-induced HepG2 cell injury. In conclusion, FA activates autophagy by promoting the expression of NRF2, thereby alleviating the development of MAFLD.

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Ethics Approval

all animal experimental protocols were approved by the Animal Ethics Committee of Yunnan Bestay Biotechnology Co., Ltd. (No. BST-RAT-20230213-01), and the animal procedures adhered to the ARRIVE guidelines 2.0.

Supporting Agencies

535 Talent Project of the First Affiliated Hospital of Kunming Medical University, Yunnan Health Training Project of High-Level Talents, Yunnan Revitalization Talent Support Program

How to Cite



1.
Wen Y, Luo J, Shi C, Wu J. Folic acid promotes autophagy to relieve metabolism-associated fatty liver disease by regulating NRF2. Eur J Histochem [Internet]. 2025 Nov. 3 [cited 2025 Dec. 26];69(4). Available from: https://www.ejh.it/ejh/article/view/4309
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