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Mingcheng Huang 1 Article
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
Jiasi Chen, Keping Wu, Yan Lei, Mingcheng Huang, Lokyu Cheng, Hui Guan, Jiawen Lin, Ming Zhong, Xiaohua Wang, Zhihua Zheng
Endocrinol Metab. 2023;38(2):226-244.   Published online April 27, 2023
DOI: https://doi.org/10.3803/EnM.2022.1604
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  • 8 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

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
  • Enhanced cell survival in prepubertal testicular tissue cryopreserved with membrane lipids and antioxidants rich cryopreservation medium
    Reyon Dcunha, Anjana Aravind, Smitha Bhaskar, Sadhana Mutalik, Srinivas Mutalik, Sneha Guruprasad Kalthur, Anujith Kumar, Padmaraj Hegde, Satish Kumar Adiga, Yulian Zhao, Nagarajan Kannan, Thottethodi Subrahmanya Keshava Prasad, Guruprasad Kalthur
    Cell and Tissue Research.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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