RT Journal Article
SR Electronic
T1 Metabolic reprogramming of fibro/adipogenic progenitors facilitates muscle regeneration
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000646
DO 10.26508/lsa.202000660
VO 3
IS 3
A1 Alessio Reggio
A1 Marco Rosina
A1 Natalie Krahmer
A1 Alessandro Palma
A1 Lucia Lisa Petrilli
A1 Giuliano Maiolatesi
A1 Giorgia Massacci
A1 Illari Salvatori
A1 Cristiana Valle
A1 Stefano Testa
A1 Cesare Gargioli
A1 Claudia Fuoco
A1 Luisa Castagnoli
A1 Gianni Cesareni
A1 Francesca Sacco
YR 2020
UL https://www.life-science-alliance.org/content/3/3/e202000646.abstract
AB 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.