title: Chronic kidney disease reduces muscle mitochondria and exercise endurance and its exacerbation by dietary protein through inactivation of pyruvate dehydrogenase.
abstract: Chronic kidney disease impairs physical performance. Here the time course and mechanism of muscle insufficiency in renal failure and the influence of dietary protein were studied using 5/6 nephrectomized C57Bl/6 mice, focusing on muscle mass and mitochondria. A decrease in muscle mitochondria and running distance was found in young (16-20 weeks) 5/6 nephrectomized mice, despite the preservation of muscle volume and power. However, a decrease in muscle volume, associated with a reduction in muscle power, was found in aged (48-52 weeks) 5/6 nephrectomized mice. A high-protein diet feeding from 8 weeks increased muscle volume and power in the mice; but this further decreased running distance. Activation of pyruvate dehydrogenase by dichloroacetate effectively recovered running distance that was decreased by dietary protein. These findings indicate the mechanism of muscle insufficiency in renal failure and suggest that activation of muscle mitochondria would serve as a potential strategy for improving the physical performance of the patients with chronic kidney disease.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Tamaki
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Miyashita
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Wakino
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Mitsuishi
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004044:Dietary Proteins / Q000009:adverse effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D017079:Exercise Tolerance / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology*; D063269:Mitochondrial Turnover / Q000187:drug effects; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology / Q000628:therapy; D012420:Running; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D016207:Cytokines; D004044:Dietary Proteins; D020536:Enzyme Activators; D018836:Inflammation Mediators; D011768:Pyruvate Dehydrogenase Complex; D003999:Dichloroacetic Acid