Open AccessFGF-2–dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis
Author(s) -
Sebastian Mathes,
Alexandra Fahrner,
Umesh Ghoshdastider,
Hannes A. Rüdiger,
Michael Leunig,
Christian Wolfrum,
Jan Krützfeldt
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2021013118
Subject(s) - skeletal muscle , adipogenesis , endocrinology , biology , adipose tissue , medicine , microbiology and biotechnology , fibroblast growth factor , myogenesis , genetics , receptor
Significance A unique feature of muscle during aging, obesity, and type 2 diabetes is the appearance of adipose tissue between skeletal muscle fibers, the intramuscular adipose tissue (IMAT). IMAT is generally associated with insulin resistance, decreased muscle strength, and, in older adults, impaired mobility. However, the molecular cues that cause the pathological formation of IMAT are currently unknown. This work uncovers a conserved FGF-2–mediated signaling axis that up-regulates the expression of microRNA-29a, triggering a decrease of the adipogenic inhibitor SPARC and increased fat formation in aged skeletal muscle. We show that FGF-2–dependent signaling modulates the fate of fibro/adipogenic progenitors and their propensity to differentiate to intramuscular adipocytes, which reveal therapeutic opportunities to prevent IMAT formation in human skeletal muscle.