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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Targeting adipose remodeling: Synergistic mechanisms of drugs and adipose-derived stem cells in obese type 2 diabetes mellitus
Cheng Luo, Xian-Mei Yu, Liang-Yan Hua, Mei-Qi Zeng, Hui Xu, Cheng-Zheng Duan, Shi-Yu Xu, Da Sun, Li-Ya Ye, Dong-Juan He
Cheng Luo, Liang-Yan Hua, Cheng-Zheng Duan, Shi-Yu Xu, Department of Endocrinology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Xian-Mei Yu, Dong-Juan He, Department of Endocrinology, The Second People’s Hospital of Quzhou, Quzhou 324002, Zhejiang Province, China
Mei-Qi Zeng, Department of Ophthalmology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Hui Xu, Department of Hospital Management, Quzhou Hospital of Traditional Chinese Medicine, Quzhou 324000, Zhejiang Province, China
Da Sun, Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325000, Zhejiang Province, China
Li-Ya Ye, Department of Gynecology, The Second People’s Hospital of Quzhou, Quzhou 324002, Zhejiang Province, China
Co-first authors: Cheng Luo and Xian-Mei Yu.
Co-corresponding authors: Li-Ya Ye and Dong-Juan He.
Author contributions: Luo C and Yu XM contributed to the conceptualization and writing of the original draft; Hua LY and Zeng MQ participated in the formal analysis and data validation; Duan CZ and Xu SY contributed to the methodology and investigation; Xu H and Sun D were involved in the supervision and project administration; Ye LY and He DJ took part in reviewing and editing; All authors participated in drafting the manuscript and have read, contributed to, and approved the final version of the manuscript. Luo C and Yu XM reviewed and summarized the literature and wrote the first draft of the paper; both authors made vital and integral contributions to the completion of the project and therefore qualify as co-first authors of the paper. Ye LY and He DJ as the corresponding authors played important and integral roles in the design of the study and the preparation of the manuscript. They supervised the study design, provided critical revisions, and ensured the integrity of the research findings. The collaboration between all authors was essential for the publication of this manuscript.
Supported by Special Fund Project for Clinical Medicine of Zhejiang Medical Association, No. 2024ZYC-Z30; and Zhejiang Provincial Traditional Chinese Medicine Science and Technology Program, No. 2025ZL144.
Conflict-of-interest statement: All 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: Dong-Juan He, MD, Chief Physician, Dean, Director, Professor, Department of Endocrinology, The Second People’s Hospital of Quzhou, No. 338 Xin’an Avenue, Qujiang District, Quzhou 324002, Zhejiang Province, China.
hedongjuan1247@wmu.edu.cn
Received: June 25, 2025
Revised: August 11, 2025
Accepted: October 9, 2025
Published online: November 26, 2025
Processing time: 154 Days and 13.8 Hours
Type 2 diabetes mellitus, particularly when accompanied by obesity, has become a major global public health burden. Visceral adipose tissue accumulation contributes to insulin resistance, lipotoxicity, and chronic inflammation, thereby accelerating metabolic deterioration. Although pharmacological agents such as pioglitazone and metformin are effective in modulating fat distribution and improving metabolic parameters, their roles in adipose tissue remodeling remain insufficiently elucidated. Recent advances in regenerative medicine have highlighted the therapeutic potential of adipose-derived stem cells, owing to their differentiation capacity, anti-inflammatory secretory profile, and involvement in metabolic homeostasis. This review summarized current pharmacological and stem cell-based strategies targeting adipose tissue dysfunction in patients with obesity and type 2 diabetes mellitus with a particular focus on the mechanistic roles of adipokines, mitochondrial dysfunction, and extracellular matrix remodeling in visceral adipose tissue. It further discussed the potential synergistic benefits of adipose-derived stem cell-based combination interventions. Finally, the review envisioned future directions for integrating molecularly targeted drugs with cell therapies in the personalized management of metabolic disorders.
Core Tip: This review explored how pharmacological agents (pioglitazone, metformin, glucagon-like peptide-1 receptor agonist, sodium-glucose cotransporter-2 inhibitors) and adipose-derived stem cells synergistically remodel dysfunctional adipose tissue in obesity-associated type 2 diabetes. It highlighted the roles of adipose browning, mitochondrial restoration, anti-inflammatory paracrine effects, and fat redistribution. By integrating metabolic drug actions with regenerative cell therapies, the review proposed a precision intervention strategy targeting insulin resistance and metabolic inflammation at the tissue level, offering translational insights for individualized treatment of diabetic obesity.
