2. Academic Validation
  3. ATGL regulates renal fibrosis by reprogramming lipid metabolism during the transition from AKI to CKD

ATGL regulates renal fibrosis by reprogramming lipid metabolism during the transition from AKI to CKD

  • Mol Ther. 2025 Feb 5;33(2):805-822. doi: 10.1016/j.ymthe.2024.12.053.
Xiaofan Li 1,  Jianwen Chen 2,  Jun Li 3,  Yixuan Zhang 1,  Jikai Xia 4,  Hongjian Du 1,  Chunjia Sheng 1,  Mengjie Huang 2,  Wanjun Shen 2,  Guangyan Cai 2,  Lingling Wu 2,  Xueyuan Bai 5,  Xiangmei Chen 6
Affiliations

Affiliations

  • 1 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing 100853, China; Chinese PLA Medical School, Beijing 100853, China.
  • 2 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing 100853, China.
  • 3 School of Basic Medical Sciences, Fudan University, Dong'An Road 130, Shanghai 200032, China.
  • 4 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing 100853, China; School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 5 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing 100853, China. Electronic address: xueyuan_bai@163.com.
  • 6 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing 100853, China. Electronic address: xmchen301@126.com.
PMID: 39748508 DOI: 10.1016/j.ymthe.2024.12.053
Abstract

Acute kidney injury (AKI) can progress to chronic kidney disease (CKD) and subsequently to renal fibrosis. Poor repair of renal tubular epithelial cells (TECs) after injury is the main cause of renal fibrosis. Studies have shown that restoring damaged fatty acid β-oxidation (FAO) can reduce renal fibrosis. Adipose triglyceride Lipase (ATGL) is a key Enzyme that regulates lipid hydrolysis. This study, for the first time, demonstrated that ATGL was downregulated in the renal TEC in the AKI-CKD transition mouse model. Moreover, treatment with the ATGL Inhibitor atglistatin exacerbated lipid accumulation and downregulated the FAO level and mitochondrial function, while it increased the level of oxidative stress injury and Apoptosis, resulting in aggravated renal fibrosis. In contrast, ATGL overexpression suppressed lipid accumulation, improved the FAO level and mitochondrial function, and attenuated oxidative stress and Apoptosis, thereby ameliorating fibrosis in vitro and in vivo. In summary, ATGL regulates renal fibrosis by reprogramming lipid metabolism in renal TECs. This study provided new avenues and targets for treating CKD.

Keywords

ATGL; acute kidney injury; chronic kidney disease; fatty acid oxidation; metabolic reprogramming.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z