Gao DJ, Zeng T, Chong YT, Li XH. Copper and hepatic lipid dysregulation: Mechanisms and implications. World J Hepatol 2025; 17(8): 107803 [DOI: 10.4254/wjh.v17.i8.107803]
Corresponding Author of This Article
Xin-Hua Li, PhD, Professor, Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou 510630, Guangdong Province, China. lixinh8@mail.sysu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Aug 27, 2025; 17(8): 107803 Published online Aug 27, 2025. doi: 10.4254/wjh.v17.i8.107803
Copper and hepatic lipid dysregulation: Mechanisms and implications
Dong-Jing Gao, Tao Zeng, Yu-Tian Chong, Xin-Hua Li
Dong-Jing Gao, Tao Zeng, Department of Infectious Diseases, Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Yu-Tian Chong, Xin-Hua Li, Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Co-first authors: Dong-Jing Gao and Tao Zeng.
Co-corresponding authors: Yu-Tian Chong and Xin-Hua Li.
Author contributions: Gao DJ and Zeng T designed the study and collaborated on manuscript preparation; Li XH and Chong YT critically reviewed the manuscript. All authors read and approved the final version. Gao DJ and Zeng T contributed equally to this work as co-first authors. Both professors participated in structuring the review, revising key arguments, and addressing academic controversies, ensuring the scientific rigor and scholarly authority of this work. The designation of two co-corresponding authors reflects their equally critical yet distinct contributions to this review article. Prof. Li XH, as my primary supervisor, provided foundational intellectual direction by identifying the mechanistic link between copper and steatosis. His expertise in refractory liver diseases shaped the article's conceptual framework and guided its development and manuscript preparation. Prof. Chong YT’s clinical expertise critically evaluated the translational relevance of copper-steatosis mechanisms in metabolic dysfunction-associated fatty liver disease, reinforcing the article's clinical implications. Given their complementary roles-Prof. Li’s theoretical leadership and Prof. Chong’s applied perspective-their co-corresponding authorship accurately represents their shared supervisory input and aligns with collaborative authorship norms in translational research. This approach also acknowledges collaboration across institutions and disciplines, ensuring equitable attribution.
Conflict-of-interest statement: The authors declare no competing interests.
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: Xin-Hua Li, PhD, Professor, Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou 510630, Guangdong Province, China. lixinh8@mail.sysu.edu.cn
Received: April 1, 2025 Revised: May 6, 2025 Accepted: July 7, 2025 Published online: August 27, 2025 Processing time: 151 Days and 18.9 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) and Wilson's disease (WD) are common clinical conditions characterized by hepatic steatosis. Copper has been associated with the progression of hepatic steatosis, but its precise mechanism remains unclear. Emerging research on hepatic copper homeostasis-including its role in liver aging, cuproptosis induction, and lipid metabolism dysregulation-highlighted its significance in liver pathophysiology. Multiple mechanisms have been implicated in copper-induced hepatic lipid metabolism abnormalities, including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, impaired glucose metabolism, AMPK activation, hepatic nuclear receptor modulation, and cuproptosis. Both copper excess and deficiency could trigger hepatic steatosis via these pathways. This review systematically summarized intracellular copper metabolism regulation, elucidated potential mechanisms of copper-induced hepatic lipid dysregulation, and analyzed copper-lipid metabolism interactions in MASLD and WD. These findings provide insights into the mechanisms by which copper contributes to hepatic steatosis and offer a theoretical basis for targeting copper homeostasis as a therapeutic strategy in the treatment of liver diseases.
Core Tip: Hepatic steatosis diseases are strongly associated with copper, and it has been shown that copper levels promote hepatic fat synthesis or lipolysis by triggering different mechanisms, which is extremely important for unravelling the molecular mechanisms of hepatic steatosis in diseases such as metabolic dysfunction-associated steatotic liver disease and Wilson's disease. This article reviews the potential mechanisms of copper-induced hepatic lipid dysregulation and explores new therapeutic targets for hepatic steatosis diseases.
