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©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
Fibroblast growth factor 1 alleviates diabetic nephropathy by reducing renal lipid accumulation in diabetic kidney
Ying-Jian Li, He-Yu Ge, Gui-Gui Zhang, Hao-Yu Chen, Yu-Jia Xi, Kai Wang, Yin-Li Huang, Chi Zhang, Xia Fan, Xiao-Qing Yan
Ying-Jian Li, Yin-Li Huang, Xiao-Qing Yan, Department of Endocrinology, Pingyang Hospital of Wenzhou Medical University, Wenzhou 325499, Zhejiang Province, China
Ying-Jian Li, He-Yu Ge, Gui-Gui Zhang, Hao-Yu Chen, Yu-Jia Xi, Xiao-Qing Yan, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
Kai Wang, Department of Cardiology, Heart Center, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Chi Zhang, Wenzhou Key Laboratory for The Diagnosis and Prevention of Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University (Ruian People’s Hospital), Wenzhou 325200, Zhejiang Province, China
Xia Fan, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China
Co-first authors: Ying-Jian Li and He-Yu Ge.
Co-corresponding authors: Xia Fan and Xiao-Qing Yan.
Author contributions: Li YJ and Ge HY had equal contribution to the present research as co-first authors; Li YJ, Ge HY and Zhang GG performed in vivo experiments in mice; Li YJ, Ge HY, Zhang GG, Chen HY, Xi YJ, Wang K and Huang YL performed in vitro cell culture, cell biology, molecular biology experiments, and histology analysis; Li YJ and Yan XQ wrote the manuscript; Zhang C and Fan X edited the manuscript with important intellectual content; Fan X and Yan XQ supervised this study and equally contributed to the present research as co-corresponding authors; all authors have read and approved the final version to be published.
Supported by National Natural Science Foundation of China, No. 82470453 and No. 82370832; Natural Science Foundation of Zhejiang Province, No. LY22H020005; and The Summit Advancement Disciplines of Zhejiang Province (Wenzhou Medical University-Pharmaceutics).
Institutional animal care and use committee statement: All animal experiments were carried out in accordance with the procedures and guidelines of the institutional animal ethics committee for animal experiments and approved by the Laboratory Animal Ethics Committee of Wenzhou Medical University, Wenzhou, Zhejiang Province, China, No. wydw2021-0643.
Conflict-of-interest statement: The authors declare no conflicts of interest.
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: The data presented in this study are available on request from the corresponding author.
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-Qing Yan, PhD, Associate Professor, School of Pharmaceutical Sciences, Wenzhou Medical University, University-Town, Wenzhou 325035, Zhejiang Pro
vince, China.
yanxiaoqing@wmu.edu.cn
Received: July 28, 2025
Revised: October 12, 2025
Accepted: November 27, 2025
Published online: February 15, 2026
Processing time: 193 Days and 4.2 Hours
BACKGROUND
Diabetic nephropathy (DN) is a major complication of diabetes, yet therapeutic strategies that specifically target its pathogenesis are still lacking.
AIM
To evaluate the therapeutic potential of fibroblast growth factor 1 (FGF1) in DN and explore its underlying mechanisms.
METHODS
DN was induced in vivo using a type 2 diabetes mouse model, and in vitro using human kidney-2 (HK-2) cells treated with high glucose and palmitate acid (HGPA). Renal function, lipid accumulation and fibrosis were evaluated by urinary albumin creatinine ratio, Oil Red O staining and adipose differentiation-related protein expression, and Sirius Red staining, respectively. Oxygen consumption rate of HGPA-treated HK-2 cells with or without FGF1 was measured using the Seahorse XF Analyzer.
RESULTS
FGF1 treatment reduced urinary albumin excretion, ameliorated glomerular hypertrophy, attenuated renal fibrosis and inflammation, and diminished lipid accumulation in diabetic kidneys. Analysis of fatty acid metabolism revealed that cluster of differentiation 36, a key regulator of long-chain fatty acids uptake, was upregulated, while carnitine palmitoyl transferase 1A, a rate-limiting enzyme in fatty acid beta-oxidation (FAO), was downregulated in diabetic kidneys and HGPA-treated HK-2 cells. FGF1 treatment normalized the expression of both cluster of differentiation 36 and carnitine palmitoyl transferase 1A and enhanced FAO in HGPA-treated HK-2 cells. Mechanistically, FGF1 restored AMP-activated protein kinase (AMPK) activity and peroxisome proliferator-activated receptor alpha expression, both of which were suppressed in DN and HGPA-treated HK-2 cells. Notably, pharmacological inhibition of AMPK or FAO abolished the protective effect of FGF1.
CONCLUSION
FGF1 alleviates DN by inhibiting fatty acid uptake and promoting lipid catabolism via AMPK activation and FAO enhancement.
Core Tip: Fibroblast growth factor 1 (FGF1) can effectively ameliorate diabetic nephropathy as reflected by improved renal function and alleviation of kidney morphological abnormalities. FGF1 alleviates renal lipid accumulation, as evidenced by decreased triglyceride content and repressed adipose differentiation-related protein expression, via inhibiting fatty acid uptake and promoting lipid catabolism in diabetic kidney. Mechanical studies demonstrated that FGF1 modulates renal lipid metabolism via restoring AMP-activated protein kinase activity and peroxisome proliferator-activated receptor alpha expression.
