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bioRxiv · 10.1101/2023.02.07.527478

Pgc-1α is an exercise-responsive regulator of myosteatosis in older individuals

Iijima, H.·Ambrosio, F.·Matsui, Y.
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Abstract

Accumulated fat in skeletal muscle, common in sedentary older individuals, compromises skeletal muscle health and function. Mechanistic understanding of how physical activity levels dictate fat accumulation represents a critical step towards establishment of therapies that promote healthy aging. Using a network paradigm that characterized the transcriptomic response of aged muscle to exercise versus immobilization protocols, this study uncovered a novel molecular cascade that regulates the fate of fibro-adipogenic progenitors (FAPs), the cell population primarily responsible for the fat accumulation. Specifically, gene set enrichment analyses (GSEA) with network propagation revealed Pgc1 as a functional hub of a large gene regulatory network underlying the regulation of FAPs by physical activity. Integrated in silico and in situ approaches to induce Pgc-1 overexpression promoted mitochondrial fatty acid oxidation and inhibited FAPs adipogenesis. These findings suggest that Pgc1 is a master regulator by which physical activity regulates fat accumulation in aged skeletal muscle. GRAPHICAL ABSTRUCT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC="FIGDIR/small/527478v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@5c4780org.highwire.dtl.DTLVardef@5a55ecorg.highwire.dtl.DTLVardef@bf1f16org.highwire.dtl.DTLVardef@192172e_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Iijima, H., Ambrosio, F., Matsui, Y.. 2023-02-08. Pgc-1α is an exercise-responsive regulator of myosteatosis in older individuals. https://doi.org/10.1101/2023.02.07.527478

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