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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Summary: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.
ISSN:2045-2322