Cell Metabolism
Volume 23, Issue 6, 14 June 2016, Pages 1078-1092
Journal home page for Cell Metabolism

Clinical and Translational Report
Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise

https://doi.org/10.1016/j.cmet.2016.05.004Get rights and content
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Highlights

  • Bone via the hormone osteocalcin improves muscle function during exercise

  • Circulating osteocalcin levels decrease in aging mice, monkeys, and humans

  • Osteocalcin promotes muscle uptake and utilization of glucose and fatty acids

  • Osteocalcin promotes muscle IL-6 secretion during exercise

Summary

Circulating levels of undercarboxylated and bioactive osteocalcin double during aerobic exercise at the time levels of insulin decrease. In contrast, circulating levels of osteocalcin plummet early during adulthood in mice, monkeys, and humans of both genders. Exploring these observations revealed that osteocalcin signaling in myofibers is necessary for adaptation to exercise by favoring uptake and catabolism of glucose and fatty acids, the main nutrients of myofibers. Osteocalcin signaling in myofibers also accounts for most of the exercise-induced release of interleukin-6, a myokine that promotes adaptation to exercise in part by driving the generation of bioactive osteocalcin. We further show that exogenous osteocalcin is sufficient to enhance the exercise capacity of young mice and to restore to 15-month-old mice the exercise capacity of 3-month-old mice. This study uncovers a bone-to-muscle feedforward endocrine axis that favors adaptation to exercise and can reverse the age-induced decline in exercise capacity.

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Present address: Integrative and Molecular Physiology Research Unit, Institut de Recherche Clinique de Montréal, Montréal, QC H2W 1R7, Canada