Abstract: FR-PO380
Therapeutic Approaches in Mitochondrial Dysfunction, Inflammation, and Autophagy in Uremic Cachexia: The Role of Aerobic Exercise
Session Information
- CKD: Mechanisms - II
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Author
- Zhang, Yumei, Shanghai Ninth people's hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Background
Chronic kidney disease (CKD) causes several systemic changes, including muscular homeostasis, and eventually results in muscle atrophy. CKD-induced muscle atrophy is highly prevalent, and exercise is well known to enhance muscle function, although the exact mechanism remains unclear.Here, we aimed to assess whether the protective effect of aerobic exercise in CKD mice was associated with mitochondrial dysfunction, autophagy or inflammation.
Methods
C57BL/6J mice were randomly allocated into 3 experimental groups: Sham, CKD, and CKD+aerobic exercise (CKD+AE). Renal function was assessed via serum creatinine and urea levels, and histological PAS and Masson staining were performed. Muscle wasting was determined based on grip strength, cross-sectional area (CSA), and MyHC protein expression. We measured mitochondrial dysfunction by assessing mtDNA, ROS and ATP production, and mitochondrial configuration. Autophagy was determined via assessments for Atg7, LC3, and SQSTM1 on western blotting. Inflammation was identified via pro-inflammatory cytokines and NLRP3 inflammasome components using real-time PCR and western blotting.
Results
CKD mice exhibited higher BUN and creatinine levels and more severe glomerulosclerosis and tubulointerstitial fibrosis, relative to the Sham group; all these effects were relieved by aerobic exercise. Moreover, grip strength, CSA, and MyHC protein expression were improved after 8 weeks of aerobic exercise. Furthermore, aerobic exercise significantly decreased MDA levels, increased SOD2 activity and ATP production, and improved mitochondrial configuration, relative to the CKD group. In addition, aerobic exercise down-regulated the overexpression of pro-inflammatory cytokines and NLRP3 inflammasome components, and balanced the mitochondrial biogenesis and autophagy.
Conclusion
Aerobic exercise may ameliorate CKD-induced muscle wasting by improving mitochondrial dysfunction, inflammation and autophagy in uremic cachexia.
Funding
- Government Support - Non-U.S.