American Diabetes Association
Browse
DB23-0811 Supplemental_online-only_material.pdf (2.67 MB)

CPT1A Protects Podocytes from Lipotoxicity and Apoptosis In Vitro and Alleviates Diabetic Nephropathy In VivoThe role of CPT1A in diabetic kidney disease

Download (2.67 MB)
figure
posted on 2024-03-20, 15:21 authored by Yajuan Xie, Qian Yuan, Ben Tang, Yaru Xie, Yiling Cao, Yang Qiu, Jieyu Zeng, Zhiwen Wang, Hua Su, Chun Zhang

Abstract

Defective fatty acid oxidation (FAO) has been implicated in diabetic kidney disease (DKD), yet little is known about the role of carnitine palmitoyltransferase-1A (CPT1A), a pivotal rate-limiting enzyme of FAO, in the progression of DKD. Here, we investigate whether CPT1A is a reliable therapeutic target for DKD. We first confirmed the downregulation expression of CPT1A in glomeruli from diabetic patients. We further evaluated the function of CPT1A in diabetic models. Overexpression of CPT1A exhibited protective effects in diabetic conditions, improving albuminuria and glomerular sclerosis, as well as mitigating glomerular lipid deposits and podocyte injury in streptozotocin-induced diabetic mice. Mechanistically, CPT1A not only fostered lipid consumption via fatty acid metabolism pathways, thereby reducing lipotoxicity, but also anchored Bcl2 to the mitochondrial membrane, thence preventing cytochrome C release and inhibiting the mitochondrial apoptotic process. Furthermore, a novel transcription factor of CPT1A, FOXA1, was identified. We elucidate the crucial role of CPT1A in mitigating podocyte injury and the progression of DKD, indicating that targeting CPT1A may be a promising avenue for DKD treatment.

Funding

Key Research and Development Program of Hubei Province x 2023BCB034

Ministry of Science and Technology of the People's Republic of China > National Key Research and Development Program of China 2021YFC2500200

Ministry of Science and Technology of the People's Republic of China > National Natural Science Foundation of China 81974096 81974097 82100729 82170773 82200808 82200841 82300786 82300843 82370728

History

Usage metrics

    Diabetes

    Categories

    Keywords

    Microvascular/Nephropathy ComplicationsCarnitine Palmitoyltransferase 1 (CPT-1)Podocyte(s)LipidApoptosis

    Licence

    CC BY-NC-SA 4.0

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC