PGC-1 alpha overexpression in the skeletal muscle results in a metabolically active microbiome which is independent of redox signaling

Abstract In this study, we investigated the potential relationship between the mitochondrial network and the microbiome using wild-type and skeletal muscle-specific PGC-1α (Pparg coactivator 1 alpha) overexpressing mice, both with and without exercise training. Basal PGC-1α levels were significantly...

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Main Authors: Erika Koltai, Soroosh Mozaffaritabar, Lei Zhou, Attila Kolonics, Atsuko Koike, Kumpei Tanisawa, Jonguk Park, Ferenc Torma, Zsolt Radak
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05594-w
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author Erika Koltai
Soroosh Mozaffaritabar
Lei Zhou
Attila Kolonics
Atsuko Koike
Kumpei Tanisawa
Jonguk Park
Ferenc Torma
Zsolt Radak
author_facet Erika Koltai
Soroosh Mozaffaritabar
Lei Zhou
Attila Kolonics
Atsuko Koike
Kumpei Tanisawa
Jonguk Park
Ferenc Torma
Zsolt Radak
author_sort Erika Koltai
collection DOAJ
description Abstract In this study, we investigated the potential relationship between the mitochondrial network and the microbiome using wild-type and skeletal muscle-specific PGC-1α (Pparg coactivator 1 alpha) overexpressing mice, both with and without exercise training. Basal PGC-1α levels were significantly higher in the skeletal muscle (J Physiol Biochem 80:329–335, 2024. https://doi.org/10.1007/s13105-024-01006-1 ) and, notably, in the colon, which is anatomically proximal to the microbiome. However, no significant changes were observed in cell signaling or mitochondria-related proteins within the colon. On the other hand, mitochondrial H₂O₂ production in the colon decreased in the PGC-1α overexpressing group. The relative abundance of several bacterial taxa differed between wild-type and PGC-1α overexpressing groups at baseline condition, indicating a shift in the microbiome milieu probably to cope with the increased metabolism, enhanced short-chain fatty acid utilization, and improved endurance capacity. Ten weeks of exercise training differentially modulated the host microbiome in PGC-1α overexpressing and wild-type mice, facilitating adaptations to a broad range of exercise-induced challenges. The results of this study provide new insights into the possible cross-talk between mitochondria and the microbiome.
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spelling doaj-art-d479207ea9ff4fd8b09b80138018aeae2025-08-20T03:45:25ZengNature PortfolioScientific Reports2045-23222025-07-011511910.1038/s41598-025-05594-wPGC-1 alpha overexpression in the skeletal muscle results in a metabolically active microbiome which is independent of redox signalingErika Koltai0Soroosh Mozaffaritabar1Lei Zhou2Attila Kolonics3Atsuko Koike4Kumpei Tanisawa5Jonguk Park6Ferenc Torma7Zsolt Radak8Research Institute of Sport Science, Hungarian University of Sport ScienceResearch Institute of Sport Science, Hungarian University of Sport ScienceResearch Institute of Sport Science, Hungarian University of Sport ScienceResearch Institute of Sport Science, Hungarian University of Sport ScienceResearch Institute of Sport Science, Hungarian University of Sport ScienceFaculty of Sport Sciences, Waseda UniversityArtificial Intelligence Center for Health and Biomedical ResearchResearch Institute of Sport Science, Hungarian University of Sport ScienceResearch Institute of Sport Science, Hungarian University of Sport ScienceAbstract In this study, we investigated the potential relationship between the mitochondrial network and the microbiome using wild-type and skeletal muscle-specific PGC-1α (Pparg coactivator 1 alpha) overexpressing mice, both with and without exercise training. Basal PGC-1α levels were significantly higher in the skeletal muscle (J Physiol Biochem 80:329–335, 2024. https://doi.org/10.1007/s13105-024-01006-1 ) and, notably, in the colon, which is anatomically proximal to the microbiome. However, no significant changes were observed in cell signaling or mitochondria-related proteins within the colon. On the other hand, mitochondrial H₂O₂ production in the colon decreased in the PGC-1α overexpressing group. The relative abundance of several bacterial taxa differed between wild-type and PGC-1α overexpressing groups at baseline condition, indicating a shift in the microbiome milieu probably to cope with the increased metabolism, enhanced short-chain fatty acid utilization, and improved endurance capacity. Ten weeks of exercise training differentially modulated the host microbiome in PGC-1α overexpressing and wild-type mice, facilitating adaptations to a broad range of exercise-induced challenges. The results of this study provide new insights into the possible cross-talk between mitochondria and the microbiome.https://doi.org/10.1038/s41598-025-05594-wMitochondriaMicrobiotaPGC-1αPhysical exerciseHost–microbial interaction
spellingShingle Erika Koltai
Soroosh Mozaffaritabar
Lei Zhou
Attila Kolonics
Atsuko Koike
Kumpei Tanisawa
Jonguk Park
Ferenc Torma
Zsolt Radak
PGC-1 alpha overexpression in the skeletal muscle results in a metabolically active microbiome which is independent of redox signaling
Scientific Reports
Mitochondria
Microbiota
PGC-1α
Physical exercise
Host–microbial interaction
title PGC-1 alpha overexpression in the skeletal muscle results in a metabolically active microbiome which is independent of redox signaling
title_full PGC-1 alpha overexpression in the skeletal muscle results in a metabolically active microbiome which is independent of redox signaling
title_fullStr PGC-1 alpha overexpression in the skeletal muscle results in a metabolically active microbiome which is independent of redox signaling
title_full_unstemmed PGC-1 alpha overexpression in the skeletal muscle results in a metabolically active microbiome which is independent of redox signaling
title_short PGC-1 alpha overexpression in the skeletal muscle results in a metabolically active microbiome which is independent of redox signaling
title_sort pgc 1 alpha overexpression in the skeletal muscle results in a metabolically active microbiome which is independent of redox signaling
topic Mitochondria
Microbiota
PGC-1α
Physical exercise
Host–microbial interaction
url https://doi.org/10.1038/s41598-025-05594-w
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