posted on 2017-08-15, 00:00authored byCaroline Barbé, Fabrice Bray, Marine Gueugneau, Stéphanie Devassine, Pascale Lause, Caroline Tokarski, Christian Rolando, Jean-Paul Thissen
Skeletal muscle,
the most abundant body tissue, plays vital roles
in locomotion and metabolism. Myostatin is a negative regulator of
skeletal muscle mass. In addition to increasing muscle mass, Myostatin
inhibition impacts muscle contractility and energy metabolism. To
decipher the mechanisms of action of the Myostatin inhibitors, we
used proteomic and transcriptomic approaches to investigate the changes
induced in skeletal muscles of transgenic mice overexpressing Follistatin,
a physiological Myostatin inhibitor. Our proteomic workflow included
a fractionation step to identify weakly expressed proteins and a comparison
of fast versus slow muscles. Functional annotation of altered proteins
supports the phenotypic changes induced by Myostatin inhibition, including
modifications in energy metabolism, fiber type, insulin and calcium
signaling, as well as membrane repair and regeneration. Less than
10% of the differentially expressed proteins were found to be also
regulated at the mRNA level but the Biological Process annotation,
and the KEGG pathways analysis of transcriptomic results shows a great
concordance with the proteomic data. Thus this study describes the
most extensive omics analysis of muscle overexpressing Follistatin,
providing molecular-level insights to explain the observed muscle
phenotypic changes.