Document Type
Article
Publication Date
11-4-2022
Abstract
Alterations in muscle structure and function in chronic kidney disease (CKD) patients are associated with poor outcomes. As key organelles in muscle cell homeostasis, mitochondrial metabolism has been studied in the context of muscle dysfunction in CKD. We conducted a study to determine the contribution of oxidative metabolism, glycolysis and fatty acid oxidation to the muscle metabolism in CKD. Mice developed CKD by exposure to adenine in the diet. Muscle of CKD mice showed significant weight loss compared to non-CKD mice, but only extensor digitorum longus (EDL) muscle showed a decreased number of fibers. There was no difference in the proportion of the various muscle fibers in CKD and non-CKD mice. Muscle of CKD mice had decreased expression of proteins associated with oxidative phosphorylation but increased expression of enzymes and transporters associated with glycolysis. In cell culture, myotubes exposed to uremic serum demonstrated decreased oxygen consumption rates (OCR) when glucose was used as substrate, conserved OCR when fatty acids were used and increased lactate production. In conclusion, mice with adenine-induced CKD developed sarcopenia and with increased glycolytic metabolism but without gross changes in fiber structure. In vitro models of uremic myopathy suggest fatty acid utilization is preserved compared to decreased glucose utilization.
Recommended Citation
Serrano, Eurico; Whitaker-Menezes, Diana; Lin, Zhao; Roche, Megan; and Martinez Cantarin, Maria Paula, "Uremic Myopathy and Mitochondrial Dysfunction in Kidney Disease" (2022). Kimmel Cancer Center Faculty Papers. Paper 95.
https://jdc.jefferson.edu/kimmelccfp/95
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
36362298
Language
English
Comments
This article is the author's final published version in International Journal of Molecular Sciences, Volume 23, Issue 21, November 2022, Article number 13515.
The published version is available at https://doi.org/10.3390/ijms232113515.
Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).