- Diabetes, obesity and metabolism
- Inhibition of Fatty Acid β-Oxidation by Fatty Acid Binding Protein 4 Induces Ferroptosis in HK2 Cells Under High Glucose Conditions
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Jiasi Chen, Keping Wu, Yan Lei, Mingcheng Huang, Lokyu Cheng, Hui Guan, Jiawen Lin, Ming Zhong, Xiaohua Wang, Zhihua Zheng
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Endocrinol Metab. 2023;38(2):226-244. Published online April 27, 2023
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DOI: https://doi.org/10.3803/EnM.2022.1604
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 Abstract
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- Background
Ferroptosis, which is caused by an iron-dependent accumulation of lipid hydroperoxides, is a type of cell death linked to diabetic kidney disease (DKD). Previous research has shown that fatty acid binding protein 4 (FABP4) is involved in the regulation of ferroptosis in diabetic retinopathy. The present study was constructed to explore the role of FABP4 in the regulation of ferroptosis in DKD.
Methods
We first detected the expression of FABP4 and proteins related to ferroptosis in renal biopsies of patients with DKD. Then, we used a FABP4 inhibitor and small interfering RNA to investigate the role of FABP4 in ferroptosis induced by high glucose in human renal proximal tubular epithelial (HG-HK2) cells.
Results
In kidney biopsies of DKD patients, the expression of FABP4 was elevated, whereas carnitine palmitoyltransferase-1A (CP-T1A), glutathione peroxidase 4, ferritin heavy chain, and ferritin light chain showed reduced expression. In HG-HK2 cells, the induction of ferroptosis was accompanied by an increase in FABP4. Inhibition of FABP4 in HG-HK2 cells changed the redox state, sup-pressing the production of reactive oxygen species, ferrous iron (Fe2+), and malondialdehyde, increasing superoxide dismutase, and reversing ferroptosis-associated mitochondrial damage. The inhibition of FABP4 also increased the expression of CPT1A, reversed lipid deposition, and restored impaired fatty acid β-oxidation. In addition, the inhibition of CPT1A could induce ferroptosis in HK2 cells.
Conclusion
Our results suggest that FABP4 mediates ferroptosis in HG-HK2 cells by inhibiting fatty acid β-oxidation.
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Citations
Citations to this article as recorded by  - Augmenter of liver regeneration knockout aggravates tubular ferroptosis and macrophage activation by regulating carnitine palmitoyltransferase‐1A‐induced lipid metabolism in diabetic nephropathy
Yuanyuan Zhang, Zheng Zhang, Lili Huang, Chunxia Wang, Pengfei Yang, Ling Zhang, Xiaohui Liao
Acta Physiologica.2024;[Epub] CrossRef - Fatty Acid Binding Protein-4 Silencing Inhibits Ferroptosis to Alleviate Lipopolysaccharide-induced Injury of Renal Tubular Epithelial Cells by Blocking Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Signaling
Suo Xu, Jiye Luo, Yanli Wang, Xiaobing Chen
Journal of Physiological Investigation.2024; 67(1): 47. CrossRef - Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications
Zhili Wu, Yanru Zhu, Wenchao Liu, Balamuralikrishnan Balasubramanian, Xiao Xu, Junhu Yao, Xinjian Lei
Antioxidants.2024; 13(3): 352. CrossRef - Investigating the Role of FABP4 in Diabetes and Obesity and the Influence of Age and Ethnicity: A Comprehensive Analysis of a Cohort from the KEDP-Study
Mohammed A. Abdalla, Jehad Abubaker, Mohamed Abu-Farha, Irina Al-Khairi, Preethi Cherian, Mohammad G. Qaddoumi, Fatema Al-Rashed, Thangavel Alphonse Thanaraj, Ahmed N. Albatineh, Fahd Al-Mulla
International Journal of Molecular Sciences.2024; 25(9): 4578. CrossRef - Mitochondrial metabolic reprogramming in diabetic kidney disease
Xiaoting Fan, Meilin Yang, Yating Lang, Shangwei Lu, Zhijuan Kong, Ying Gao, Ning Shen, Dongdong Zhang, Zhimei Lv
Cell Death & Disease.2024;[Epub] CrossRef - Inhibition of FABP4 Ameliorates IL-13-Induced Inflammatory Response and Barrier Dysfunction in Nasal Mucosal Epithelial Cells through the Regulation of Ferroptosis
Shanshan Qi
Cell Biochemistry and Biophysics.2024;[Epub] CrossRef - Mechanisms and regulations of ferroptosis
Xu-Dong Zhang, Zhong-Yuan Liu, Mao-Sen Wang, Yu-Xiang Guo, Xiang-Kun Wang, Kai Luo, Shuai Huang, Ren-Feng Li
Frontiers in Immunology.2023;[Epub] CrossRef - Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases
Yumin Wang, Jing Hu, Shuang Wu, Joshua S. Fleishman, Yulin Li, Yinshi Xu, Wailong Zou, Jinhua Wang, Yukuan Feng, Jichao Chen, Hongquan Wang
Signal Transduction and Targeted Therapy.2023;[Epub] CrossRef
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