Exercise alleviates diabetic kidney disease through PPARδ-CPT1α pathway-dependent fatty acid β-oxidation

Li Xiang; Li Wang; Yin Xia; Yu Wang; Jingchun Shi; Cheng-Lin Zhang; Liping Xie; Yi Ru; Chak Kwong Cheng; Yujie Pu; Libing Hu; Junli Liu; Suowen Xu; Zongwei Cai; Yu Huang

doi:10.59717/j.xinn-life.2024.100065

The Innovation Life > 2024 Vol. 2 > No. 2 > 100065

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Exercise alleviates diabetic kidney disease through PPARδ-CPT1α pathway-dependent fatty acid β-oxidation

1.
State Key Laboratory of Environmental and Biological Analysis and Department of Chemistry, Hong Kong Baptist University, Hong Kong 999077, China
2.
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong 999077, China
3.
School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China
4.
Department of Endocrinology, Shenzhen University General Hospital, Shenzhen 518000, China
5.
Department of Pathophysiology, Shenzhen University, Shenzhen 518000, China
6.
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Nanjing Medical University, Nanjing 210000, China
7.
Department of Urology, Yan`an Affiliated Hospital of Kunming Medical University, Kunming 650051, China
8.
Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
9.
Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230000, China
10.
These authors contributed equally

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Corresponding authors: zwcai@hkbu.edu.hk (Z.C.); yu.huang@cityu.edu.hk (Y.H.)
Received Date: January 15, 2024

Accepted Date: May 14, 2024

Published Online: May 17, 2024

The Innovation Life 2(2), https://doi.org/10.59717/j.xinn-life.2024.100065 | Cite this article

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Regular physical exercise is an effective strategy in alleviating diabetic kidney disease.
  
  Exercise restores renal function in diabetic mice through enhancing PPARδ-CPT1α-dependent fatty acid β-oxidation.
  
  Reveal an unappreciated link between exercise and the restoration of renal function in diabetic kidney disease.
  
  Could potentially become a new target for therapeutic intervention against diabetic kidney disease.

ABSTRACT

ABSTRACT

Diabetic kidney disease (DKD), a severe diabetic complication affecting approximately one-third of diabetic patients, is the leading cause of end-stage chronic kidney disease. The benefits of regular exercise for patients with DKD have been well documented, particularly in overweight patients with DKD. However, the underlying mechanisms are incompletely understood. The present study demonstrates that exercise improves kidney function in diabetic db/db mice through activating PPARδ-mediated fatty acid β-oxidation (FAO). Twelve-week treadmill running exercise improved kidney function in db/db mice. Metabolomics and transcriptomics profiling analysis collectively revealed that dysregulation of FAO in db/db mice was largely corrected by running exercise. KEGG pathway enrichment revealed that PPAR pathway, a critical signalling cascade in FAO and exercise, is involved in DKD, suggesting PPARδ activation protects renal function through promoting FAO. Which was confirmed by improved renal function and enhanced FAO in db/db mice treated with PPARδ agonist GW501516. Oppositely, PPARδ-specific inhibitor GSK0660 abolished exercise-mediated improvement in renal function and FAO. In combining with gene expression profiling data we identified CPT1α, the rate-limiting enzyme in fatty acid oxidation, was suppressed in the kidney of diabetic mice and reversed by exercise and the PPARδ agonist GW501516. The findings hint at a potential role for the PPARδ-CPT1α pathway in exercise-induced improvements in diabetic renal function and may warrant further exploration of the PPARδ-CPT1α pathway as a therapeutic target in DKD.

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Xiang L., Wang L., Xia Y., et al., (2024). Exercise alleviates diabetic kidney disease through PPARδ-CPT1α pathway-dependent fatty acid β-oxidation. The Innovation Life 2(2): 100065. https://doi.org/10.59717/j.xinn-life.2024.100065

Xiang L., Wang L., Xia Y., et al., (2024). Exercise alleviates diabetic kidney disease through PPARδ-CPT1α pathway-dependent fatty acid β-oxidation. The Innovation Life 2(2): 100065. https://doi.org/10.59717/j.xinn-life.2024.100065

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Exercise alleviates diabetic kidney disease through PPARδ-CPT1α pathway-dependent fatty acid β-oxidation

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Exercise alleviates diabetic kidney disease through PPARδ-CPT1α pathway-dependent fatty acid β-oxidation

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