Enhanced myogenesis in adult muscle by transgenic expression of myostatin propeptide

Myostatin, a member of transforming growth factors-beta, is a negative regulator of muscle growth in mammals. Previous studies revealed that transgenic mice expressing myostatin propeptide had enhanced muscle mass. The transgenic mice had no significant gain of adipose tissue, and more importantly, did not display insulin resistance after undergoing a high-fat diet during adulthood. The objective of this study was to investigate the mechanisms by which myostatin propeptide depressed myostin activity. We employed immunohistochemistry procedures to study myostatin expression in muscle tissue using the transgenic mice and their wild-type littermate controls. Our experiments illustrate that even with a normal diet, the transgenic mice with enlarged muscle mass showed less adipose tissue accumulation compared with that of the wild type mice. The immunohistochemistry staining of the muscles located the target sites for myostatin and myostatin propeptide expression, showing that propeptide upregulations does not interfere with myostatin protein levels, while the effects of such myostatin disruption in transgenic mice was further demonstrated with hematoxylin and eosin staining of the muscles and adipose tissues. Our nuclei count suggested that adult transgenic mice are still in active myogenesis to promote faster muscle growth. This research provides molecular and cellular evidence for enhanced muscle growth through depressing myostatin by its propeptide, which may help establish physical activity as an effective means for preventing obesity and type 2 diabetes.