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World J Hepatol. Oct 27, 2025; 17(10): 109898
Published online Oct 27, 2025. doi: 10.4254/wjh.v17.i10.109898
Published online Oct 27, 2025. doi: 10.4254/wjh.v17.i10.109898
Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications
Su-Qun Li, Jin-Hua Wu, Ying Zhou, Chen-Xi Wang, Li Xie, Si-Ying Liu, Yu-Zhi Su, Wei He, Yi-Huai He, Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
Huan Chen, Department of Endocrinology, First People’s Hospital of Zunyi (Third Affiliated Hospital of Zunyi Medical University), Zunyi 563000, Guizhou Province, China
Wei-Wei Zhong, Department of Gastroenterology, Jingmen Central Hospital, Jingmen Central Hospital Affiliated to Jingchu University of Technology, Jingmen 448000, Hubei Province, China
Co-first authors: Su-Qun Li and Jin-Hua Wu.
Co-corresponding authors: Wei-Wei Zhong and Yi-Huai He.
Author contributions: Li SQ and Wu JH contributed equally to this work and are co-first authors. Li SQ, Wu JH, Zhou Y, Wang CX, Xie L, Liu SY, Su YZ, He W, Chen H, Zhong WW, and He YH contributed to this paper; Li SQ, Wu JH, and He YH designed the overall concept and outline of the manuscript, and contributed to the writing and editing of the manuscript and the literature review; Zhou Y, Wang CX, Xie L, Liu SY, Su YZ, He W, Chen H, and Zhong WW contributed to the discussion and design of the manuscript; He YH revised the manuscript. Zhong WW and He YH contributed equally to this work and are co-corresponding authors. All authors have read and approved the final manuscript.
Supported by the Science and Technology Planning Projects of Guizhou Province, No. QKHJC-MS[2025]384; the Science and Technology Planning Projects of Zunyi City, No. ZSKHHZ(2023)470; the WBE Liver Fibrosis Foundation, No. CFHPC2025028; Chinese Foundation for Hepatitis Prevention and Control Muxin Research Fund of Chronic Hepatitis B, No. MX202404; Beijing Liver and Gallbladder Mutual Aid Public Welfare Foundation Artificial Liver Special Fund, No. iGandanF-1082024-RGG018; and the Student Innovation and Entrepreneurship Training Program of Zunyi Medical University, No. 2024106610923.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Yi-Huai He, MD, Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, No. 201 Dalian Street, Zunyi 563000, Guizhou Province, China. 993565989@qq.com
Received: May 26, 2025
Revised: June 25, 2025
Accepted: September 11, 2025
Published online: October 27, 2025
Processing time: 156 Days and 0.9 Hours
Revised: June 25, 2025
Accepted: September 11, 2025
Published online: October 27, 2025
Processing time: 156 Days and 0.9 Hours
Core Tip
Core Tip: Abnormal hepatic triglyceride deposition is the hallmark of metabolic dysfunction-associated steatotic liver disease. While this process may originate either as a hepatic manifestation of systemic metabolic dysfunction or direct local hepatic lipid metabolic imbalance, the two pathways dynamically interact to drive disease progression. Hepatocyte nuclear factors (HNFs) regulate hepatic triglyceride metabolism via transcriptional networks, and their dysfunction constitutes a key driver of metabolic dysfunction-associated steatotic liver disease pathogenesis. Targeting critical nodes in HNF regulatory networks presents new opportunities for precision therapy. This review systematically analyzes the clinical challenges involved in HNF-targeted therapies and explores potential solutions.