Abstract: PUB559
Effects of Irisin Secretion on the Development of Kidney Injury in a Mouse Model of Uremic Sarcopenia
Session Information
Category: CKD (Non-Dialysis)
- 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Okuma, Teruyuki, Shimane Daigaku Igakubu Fuzoku Byoin, Izumo, Shimane, Japan
- Ueda, Seiji, Shimane Daigaku Igakubu Fuzoku Byoin, Izumo, Shimane, Japan
- Nagasawa, Hajime, Shimane Daigaku Igakubu Fuzoku Byoin, Izumo, Shimane, Japan
- Suzuki, Yusuke, Juntendo Daigaku, Bunkyo-ku, Tokyo, Japan
Background
The prevalence of sarcopenia is high in patients with chronic kidney disease (CKD). Sarcopenia is known to be closely associated with reduced physical activity and mortality. Recently, it has been reported that skeletal muscles after exercise secrete bioactive substances called myokines, which are associated with metabolic improvement and muscle mass increase. Irisin, one of myokines has been found to play an important role in maintaining endothelial function and is believed to be a factor for the development of atherosclerotic vascular diseases in patients with sarcopenia. In CKD condition, Irisin is reported to be decreased and its levels are associated with the severity of atherosclerosis. We investigated the impacts of exercise on Irisin kinetics and the role of Irisin in the development of renal injury in a mouse model of uremic sarcopenia.
Methods
We performed 5/6 nephrectomy on C57BL/6J mice as a model of uremic sarcopenia and treated them with or without exercise intervention for 8 weeks. And kaempferia parviflora (KP) which is an activator of SIRT1 was also tested to investigate the involvements of SIRT1-PCG1α-Irisin axis in uremic sarcopenic condition. We measured serum Irisin, the expression levels of FNDC5 (a precursor of Irisin), SIRT1-PCG1α expressions in skeletal muscle, muscle mass, grip strength, renal function, pathological changes, and especially endothelial damage.
Results
The expression levels of SIRT1, PGC1α and FNDC5 in the skeletal muscles of CKD model mice were significantly decreased. In addition, glomerular endothelial damage assessed by glycocalyx staining were observed in the CKD model mice along with a decrease in serum Irisin levels. Exercise intervention not only improved FNDC5 expression and serum Irisin levels but also halted progressive renal function loss by promoting eNOS activation and improving glomerular endothelial injury. Further, KP administration ameliorated the decreased levels of SIRT1-PGC1α in CKD model mice and subsequently enhanced FNDC5 expression and Irisin release, thus contributing to the prevention of endothelial injury and renal damage.
Conclusion
Exercise intervention and KP administration may activate the SIRT1-PGC1α axis and promote Irisin secretion, and thereby contributing to the prevention of endothelial dysfunction and halting the progression of renal damage in CKD.