Basic Study
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World J Hepatol. Feb 27, 2025; 17(2): 101691
Published online Feb 27, 2025. doi: 10.4254/wjh.v17.i2.101691
ILF3 inhibits p-AMPK expression to drive non-alcoholic fatty liver disease progression
Ting Zhan, Jia-Xi Liu, Min Huang, Ming-Tao Chen, Xiao-Rong Tian, Xiu-Lin Yang, Jie Tan, Yan-Li Zou, Zheng Han, Wei Chen, Xia Tian, Xiao-Dong Huang
Ting Zhan, Jia-Xi Liu, Min Huang, Ming-Tao Chen, Xiao-Rong Tian, Xiu-Lin Yang, Jie Tan, Yan-Li Zou, Zheng Han, Wei Chen, Xia Tian, Xiao-Dong Huang, Department of Gastroenterology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan 430000, Hubei Province, China
Co-first authors: Ting Zhan and Jia-Xi Liu.
Co-corresponding authors: Xia Tian and Xiao-Dong Huang.
Author contributions: Zhan T, Liu JX, Tian X and Huang XD conceptualized and designed the research; Zhan T, Liu JX, Huang M, Chen MT and Tian XR screened patients and acquired clinical data; Yang XL, Tan J, Zou YL, Han Z and Chen W collected blood specimen and performed laboratory analysis; Zhan T, Liu JX, Tian X and Huang XD performed data analysis; Zhan T and Liu JX wrote the paper; All the authors have read and approved the final manuscript. Zhan T proposed, designed and conducted serum amino acids analysis, performed data analysis and prepared the first draft of the manuscript. Liu JX was responsible for patient screening, enrollment, collection of clinical data and blood specimens. Both authors have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper. Both Tian X and Huang XD have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors. Huang XD conceptualized, designed, and supervised the whole process of the project. She searched the literature, revised and submitted the early version of the manuscript with the focus on the association between ILF3 and non-alcoholic fatty liver disease. Tian X applied for and obtained the funds for this research project. Tian X was instrumental and responsible for data re-analysis and re-interpretation, figure plotting, comprehensive literature search, preparation and submission of the current version of the manuscript. This collaboration between Tian X and Huang XD is crucial for the publication of this manuscript and other manuscripts still in preparation.
Supported by the Wuhan Science and Technology Bureau Project, No. 2022020801020552 (to Zhan T); and Wuhan Health and Family Planning Commission Medical Research Project, No. WX20M01 (to Tian X).
Institutional review board statement: The research was conducted based on the ethical standards and was authorized with the Ethics Committee of Wuhan Third Hospital (Approval No. 2021-006, on March 4, 2021). Sign the informed consent form after informing the patients about the contents of the experiment and the grouping.
Institutional animal care and use committee statement: These procedures adhered to the "Principles of Laboratory Animal Care" outlined by the National Institutes of Health, and the Ethics Committee of Wuhan Third Hospital approved the study (Approval No. SY2022-054, on December 23, 2022).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Sequence files and metadata for all samples used in this study have been deposited in Figshare (DOI: 10.6084/m9.figshare.25343077).
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Dong Huang, Professor, Department of Gastroenterology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Pengliuyang Road, Wuchang District, Wuhan 430000, Hubei Province, China. 13297056720@163.com
Received: September 24, 2024
Revised: December 3, 2024
Accepted: January 21, 2025
Published online: February 27, 2025
Processing time: 149 Days and 18.4 Hours
Abstract
BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is a disease of increasing global prevalence and an important risk factor for the development of insulin resistance, type 2 diabetes, non-alcoholic steatohepatitis and hepatocellular carcinoma, but the pathogenesis is not clear. The aim of this study was to explore the role of ILF3 in NAFLD.

AIM

To investigate the molecular processes through which ILF3 facilitates the advancement of NAFLD by inhibiting the expression of p-AMPK. This exploration seeks to provide new insights into the etiology of NAFLD and evaluate the potential of ILF3 as a diagnostic marker and potential treatment focus for future interventions.

METHODS

In vitro and in vivo experiments were conducted using HepG2 cells and NAFLD animal models. The effects of ILF3 knockdown on lipid synthesis and triglyceride (TG) secretion were examined by analyzing the expression levels of p-AMPK. Additionally, the roles of ILF3 and the AMPK signaling pathway were verified using techniques such as Western blotting, quantitative reverse transcription PCR, Oil Red O staining, and immunohistochemistry.

RESULTS

Investigations revealed an increase in ILF3 Levels within both HepG2 cells and animal models of NAFLD, concurrently with a decrease in p-AMPK expression. Knocking down ILF3 activated the AMPK pathway, reducing lipid production and TG secretion in hepatocytes, thereby mitigating the advancement of NAFLD.

CONCLUSION

ILF3 promotes the evolution of NAFLD by inhibiting the expression of p-AMPK. The knockdown of ILF3 activates the AMPK signaling pathway, alleviating the severity of NAFLD. These findings underscore the function of ILF3 in the pathogenesis of NAFLD and demonstrate its viability as a treatment focus and diagnostic indicator.

Keywords: Non-alcoholic fatty liver disease; ILF3; AMPK pathway; Lipid metabolism; Therapeutic target; Molecular mechanism

Core Tip: First, a correlation is found between ILF3 expression and non-alcoholic fatty liver disease (NAFLD). Second, high ILF3 expression in NAFLD patients suggests its involvement in disease progression. Third, inhibiting ILF3 expression reduces lipid deposition and triglyceride secretion in NAFLD, regulating lipid metabolism. Fourth, suppressing ILF3 stimulates the AMPK pathway, which governs the hepatic energy equilibrium and lipid processing. Fifth, ILF3 modulates the AMPK pathway as a viable therapeutic candidate for NAFLD, providing new perspectives on diagnosis and treatment.