BoneKEy Reports | BoneKEy Watch

NCoR1 builds bigger muscles in mice

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DOI:10.1038/bonekey.2012.16

Germline mutations that knock out the nuclear receptor corepressor 1 (NCoR1) are known to be lethal yet when Yamamoto et al. generated muscle-specific NCoR1 null mice, they found the animals were fitter than their wild type counterparts. Muscle-specific NCoR1 null mice had increased muscle mass, a greater number and activity of mitochondria in their muscle cells and showed a remarkably enhanced capacity for exercise.

This phenotypic change appeared to be mediated by activation of MEF2, PPARβ/δ and ERRs, all of which are transcription factors that control muscle function. The change represented a shift in the muscle fibres to become more oxidative in nature.

NCoR1 expression was also reduced when fat oxidation increased, and C. elegans with a muscle-specific knockdown of the NCoR1 homolog showed an improvement in muscular mitochondrial activity. These additional findings helped to confirm NCoR1 as a key physiological regulator of muscle mass and function.

Editor's comment: Sarcopenia, a loss of muscle mass and strength, is a major contributor to falls and fracture risk. Gaining a better understanding of how muscle mass and metabolism is regulated is therefore of major interest. New therapeutic targets for sarcopenia may be suggested by the finding that mice with skeletal muscle lacking the corepressor NCoR1 have bigger muscles and improved exercise endurance.

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