Cargando…
Skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-CoA during muscle fatigue in 5/6 nephrectomized rats
Chronic kidney disease (CKD)-related cachexia increases the risks of reduced physical activity and mortality. However, the physiological phenotype of skeletal muscle fatigue and changes in intramuscular metabolites during muscle fatigue in CKD-related cachexia remain unclear. In the present study, w...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Physiological Society
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642514/ https://www.ncbi.nlm.nih.gov/pubmed/37560765 http://dx.doi.org/10.1152/japplphysiol.00226.2023 |
_version_ | 1785146983893172224 |
---|---|
author | Fusagawa, Hiroyori Sato, Tatsuya Yamada, Takashi Ashida, Yuki Kimura, Iori Naito, Azuma Tokuda, Nao Yamauchi, Nao Ichise, Nobutoshi Terashima, Yoshinori Ogon, Izaya Teramoto, Atsushi Yamashita, Toshihiko Tohse, Noritsugu |
author_facet | Fusagawa, Hiroyori Sato, Tatsuya Yamada, Takashi Ashida, Yuki Kimura, Iori Naito, Azuma Tokuda, Nao Yamauchi, Nao Ichise, Nobutoshi Terashima, Yoshinori Ogon, Izaya Teramoto, Atsushi Yamashita, Toshihiko Tohse, Noritsugu |
author_sort | Fusagawa, Hiroyori |
collection | PubMed |
description | Chronic kidney disease (CKD)-related cachexia increases the risks of reduced physical activity and mortality. However, the physiological phenotype of skeletal muscle fatigue and changes in intramuscular metabolites during muscle fatigue in CKD-related cachexia remain unclear. In the present study, we performed detailed muscle physiological evaluation, analysis of mitochondrial function, and comprehensive analysis of metabolic changes before and after muscle fatigue in a 5/6 nephrectomized rat model of CKD. Wistar rats were randomized to a sham-operation (Sham) group that served as a control group or a 5/6 nephrectomy (Nx) group. Eight weeks after the operation, in situ torque and force measurements in plantar flexor muscles in Nx rats using electrical stimulation revealed a significant decrease in muscle endurance during subacute phase related to mitochondrial function. Muscle mass was reduced without changes in the proportions of fiber type-specific myosin heavy chain isoforms in Nx rats. Pyruvate-malate-driven state 3 respiration in isolated mitochondria was impaired in Nx rats. Protein expression levels of mitochondrial respiratory chain complexes III and V were decreased in Nx rats. Metabolome analysis revealed that the increased supply of acetyl CoA in response to fatigue was blunted in Nx rats. These findings suggest that CKD deteriorates skeletal muscle endurance in association with mitochondrial dysfunction and inadequate supply of acetyl-CoA during muscle fatigue. NEW & NOTEWORTHY Mitochondrial dysfunction is associated with decreased skeletal muscle endurance in chronic kidney disease (CKD), but the muscle physiological phenotype and major changes in intramuscular metabolites during muscle fatigue in CKD-related cachexia remain unclear. By using a 5/6 nephrectomized CKD rat model, the present study revealed that CKD is associated with reduced tetanic force in response to repetitive stimuli in a subacute phase, impaired mitochondrial respiration, and inadequate supply of acetyl-CoA during muscle fatigue. |
format | Online Article Text |
id | pubmed-10642514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Physiological Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-106425142023-11-15 Skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-CoA during muscle fatigue in 5/6 nephrectomized rats Fusagawa, Hiroyori Sato, Tatsuya Yamada, Takashi Ashida, Yuki Kimura, Iori Naito, Azuma Tokuda, Nao Yamauchi, Nao Ichise, Nobutoshi Terashima, Yoshinori Ogon, Izaya Teramoto, Atsushi Yamashita, Toshihiko Tohse, Noritsugu J Appl Physiol (1985) Research Article Chronic kidney disease (CKD)-related cachexia increases the risks of reduced physical activity and mortality. However, the physiological phenotype of skeletal muscle fatigue and changes in intramuscular metabolites during muscle fatigue in CKD-related cachexia remain unclear. In the present study, we performed detailed muscle physiological evaluation, analysis of mitochondrial function, and comprehensive analysis of metabolic changes before and after muscle fatigue in a 5/6 nephrectomized rat model of CKD. Wistar rats were randomized to a sham-operation (Sham) group that served as a control group or a 5/6 nephrectomy (Nx) group. Eight weeks after the operation, in situ torque and force measurements in plantar flexor muscles in Nx rats using electrical stimulation revealed a significant decrease in muscle endurance during subacute phase related to mitochondrial function. Muscle mass was reduced without changes in the proportions of fiber type-specific myosin heavy chain isoforms in Nx rats. Pyruvate-malate-driven state 3 respiration in isolated mitochondria was impaired in Nx rats. Protein expression levels of mitochondrial respiratory chain complexes III and V were decreased in Nx rats. Metabolome analysis revealed that the increased supply of acetyl CoA in response to fatigue was blunted in Nx rats. These findings suggest that CKD deteriorates skeletal muscle endurance in association with mitochondrial dysfunction and inadequate supply of acetyl-CoA during muscle fatigue. NEW & NOTEWORTHY Mitochondrial dysfunction is associated with decreased skeletal muscle endurance in chronic kidney disease (CKD), but the muscle physiological phenotype and major changes in intramuscular metabolites during muscle fatigue in CKD-related cachexia remain unclear. By using a 5/6 nephrectomized CKD rat model, the present study revealed that CKD is associated with reduced tetanic force in response to repetitive stimuli in a subacute phase, impaired mitochondrial respiration, and inadequate supply of acetyl-CoA during muscle fatigue. American Physiological Society 2023-10-01 2023-08-10 /pmc/articles/PMC10642514/ /pubmed/37560765 http://dx.doi.org/10.1152/japplphysiol.00226.2023 Text en Copyright © 2023 The Authors. https://creativecommons.org/licenses/by/4.0/Licensed under Creative Commons Attribution CC-BY 4.0 (https://creativecommons.org/licenses/by/4.0/) . Published by the American Physiological Society. |
spellingShingle | Research Article Fusagawa, Hiroyori Sato, Tatsuya Yamada, Takashi Ashida, Yuki Kimura, Iori Naito, Azuma Tokuda, Nao Yamauchi, Nao Ichise, Nobutoshi Terashima, Yoshinori Ogon, Izaya Teramoto, Atsushi Yamashita, Toshihiko Tohse, Noritsugu Skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-CoA during muscle fatigue in 5/6 nephrectomized rats |
title | Skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-CoA during muscle fatigue in 5/6 nephrectomized rats |
title_full | Skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-CoA during muscle fatigue in 5/6 nephrectomized rats |
title_fullStr | Skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-CoA during muscle fatigue in 5/6 nephrectomized rats |
title_full_unstemmed | Skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-CoA during muscle fatigue in 5/6 nephrectomized rats |
title_short | Skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-CoA during muscle fatigue in 5/6 nephrectomized rats |
title_sort | skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-coa during muscle fatigue in 5/6 nephrectomized rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642514/ https://www.ncbi.nlm.nih.gov/pubmed/37560765 http://dx.doi.org/10.1152/japplphysiol.00226.2023 |
work_keys_str_mv | AT fusagawahiroyori skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT satotatsuya skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT yamadatakashi skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT ashidayuki skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT kimuraiori skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT naitoazuma skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT tokudanao skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT yamauchinao skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT ichisenobutoshi skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT terashimayoshinori skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT ogonizaya skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT teramotoatsushi skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT yamashitatoshihiko skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats AT tohsenoritsugu skeletalmuscleendurancedeclineswithimpairedmitochondrialrespirationandinadequatesupplyofacetylcoaduringmusclefatiguein56nephrectomizedrats |