Endocrine Abstracts

Background: Chronic kidney disease (CKD) in human has been believed to decrease muscle weight and physical performance. High protein diet would increase muscle mass and strength especially in athletes, but is not recommended for CKD patients because of the risk for exacerbation of uremia. Therefore, we investigated the muscle character especially focused on the mitochondrial activity and physical performance in 5/6 nephrectomy CKD model mice, which fed on different protein contents in diets.

Methods: C57bl/6 mice which were 5/6 nephrectomized at 6–7 weeks old were fed on diets containing 3–50%Kcal protein. Muscle strength and exercise endurance were examined at 16 weeks old. Muscle weight, the mitochondrial activity, and the phospholization levels of S6K1 and AMPK were examined at 20 weeks old. C2C12 myotubular cells were treated with amino acids cocktail and investigated for mitochondrial energy metabolism.

Results: Exercise endurance was decreased in 5/6 nephrectomized mice at 16 weeks old with decreasing phosphlization level of AMPK and mitochondrial amount in skeletal muscle, although muscle weight and strength were preserved. Exercise endurance and mitochondrial function were further decreased in 30% Kcal protein diet group compared with 10% Kcal protein group. Serum lactate level after exercise was remarkably elevated in the high-protein diet group, associated with a decrease in muscle pyruvate dehydrogenase (PDH) activity. Amino acids cocktail treatment in the C2C12 cells decreased oxygen utilization and ATP content and increased lactate level in the culture medium, associated with a decrease in the PDH activity.

Conclusion: We found that muscle mitochondrial amount and exercise endurance were decreased in 5/6 nephrectomy CKD model mice at 16 weeks old, associated with a decrease in muscle AMPK phospholization and mitochondrial amount. A protein-restricted diet containing 10% Kcal protein contributed to maintain exercise endurance in the CKD model mice.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.