Zhang CY, Liu S, Yang M. Macrophage and inflammation in diabetes and metabolic dysfunction-associated steatotic liver disease: From mechanisms to therapeutic strategies. World J Diabetes 2025; 16(9): 110515 [DOI: 10.4239/wjd.v16.i9.110515]
Corresponding Author of This Article
Ming Yang, PhD, Assistant Professor, Department of Surgery, University of Connecticut, School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, United States. minyang@uchc.edu
Research Domain of This Article
Endocrinology & Metabolism
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 Diabetes. Sep 15, 2025; 16(9): 110515 Published online Sep 15, 2025. doi: 10.4239/wjd.v16.i9.110515
Macrophage and inflammation in diabetes and metabolic dysfunction-associated steatotic liver disease: From mechanisms to therapeutic strategies
Chun-Ye Zhang, Shuai Liu, Ming Yang
Chun-Ye Zhang, Bond Life Sciences Center, University of Missouri, Columbia, MO 65212, United States
Shuai Liu, The First Affiliated Hospital, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
Ming Yang, Department of Surgery, University of Connecticut, School of Medicine, Farmington, CT 06030, United States
Author contributions: Zhang CY, Liu S, and Yang M designed, wrote, revised, and finalized the manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Ming Yang, PhD, Assistant Professor, Department of Surgery, University of Connecticut, School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, United States. minyang@uchc.edu
Received: June 9, 2025 Revised: July 8, 2025 Accepted: August 26, 2025 Published online: September 15, 2025 Processing time: 95 Days and 18.9 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is featured by the accumulation of excessive fat in the liver. It is caused by many factors, such as overweight, obesity, diabetes, and high plasma levels of sugar, cholesterol, and triglycerides. MASLD is commonly associated with type 2 diabetes (T2D), which is characterized by a pathophysiological deficiency of insulin secretion due to impaired function of pancreatic β cells and insulin resistance. T2D has become a global pandemic that influences more than 21.7 million people worldwide. Pre-clinical and clinical studies have been performed to investigate molecular crosslinks between T2D and MASLD and their therapeutic strategies. Accumulating evidence has demonstrated that macrophages are cellular mediators that contribute to the progression of MASLD and T2D by impacting the resolution of inflammation. Different types of macrophages are involved in the pathogenesis of MASLD and T2D, including liver-resident macrophages or Kupffer cells, monocyte-derived macrophages, and adipose tissue macrophages. These macrophages secrete enzymes, chemokines, cytokines, as well as exosomes, to induce metabolic inflammation and insulin resistance, immune cell infiltration, and tissue injury. In this review, we provide a comprehensive summary of the molecular and cellular interactions between MASLD and T2D with a specific discussion of the critical roles of macrophages and inflammation. The underlying molecular mechanisms and the associated therapeutic targets and strategies are also reviewed.
Core Tip: Macrophages are an important cellular component that regulates metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D). Macrophage-derived cytokines, chemokines, and metabolic products contribute to metabolic inflammation and insulin resistance, immune cell infiltration, and tissue injury. The phenotype and function of macrophages are important factors for evaluating the efficacy of MASLD and T2D treatments. Clinical trials are ongoing to dissect the roles of macrophages and test macrophage-targeted therapies in MASLD, T2D, and other related metabolic disorders.
