Metabolic reprogramming of fibro/adipogenic progenitors facilitates muscle regeneration

Alessio Reggio, Marco Rosina, Natalie Krahmer, Alessandro Palma, Lucia Lisa Petrilli, Giuliano Maiolatesi, Giorgia Massacci, Illari Salvatori, Cristiana Valle, Stefano Testa, Cesare Gargioli, Claudia Fuoco, Luisa Castagnoli, Gianni Cesareni, Francesca Sacco

Research output: Contribution to journalArticle

Abstract

In Duchenne muscular dystrophy (DMD), the absence of the dystrophin protein causes a variety of poorly understood secondary effects. Notably, muscle fibers of dystrophic individuals are characterized by mitochondrial dysfunctions, as revealed by a reduced ATP production rate and by defective oxidative phosphorylation. Here, we show that in a mouse model of DMD (mdx), fibro/adipogenic progenitors (FAPs) are characterized by a dysfunctional mitochondrial metabolism which correlates with increased adipogenic potential. Using high-sensitivity mass spectrometry-based proteomics, we report that a short-term high-fat diet (HFD) reprograms dystrophic FAP metabolism in vivo. By combining our proteomic dataset with a literature-derived signaling network, we revealed that HFD modulates the β-catenin-follistatin axis. These changes are accompanied by significant amelioration of the histological phenotype in dystrophic mice. Transplantation of purified FAPs from HFD-fed mice into the muscles of dystrophic recipients demonstrates that modulation of FAP metabolism can be functional to ameliorate the dystrophic phenotype. Our study supports metabolic reprogramming of muscle interstitial progenitor cells as a novel approach to alleviate some of the adverse outcomes of DMD.

Original languageEnglish
JournalLife Science Alliance
Volume3
Issue number3
DOIs
Publication statusPublished - Mar 1 2020

ASJC Scopus subject areas

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

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    Reggio, A., Rosina, M., Krahmer, N., Palma, A., Petrilli, L. L., Maiolatesi, G., Massacci, G., Salvatori, I., Valle, C., Testa, S., Gargioli, C., Fuoco, C., Castagnoli, L., Cesareni, G., & Sacco, F. (2020). Metabolic reprogramming of fibro/adipogenic progenitors facilitates muscle regeneration. Life Science Alliance, 3(3). https://doi.org/10.26508/lsa.202000660