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

Paula Mera, Kathrin Laue, Mathieu Ferron, Cyril Confavreux, Jianwen Wei, Marta Galán-Díez, Alain Lacampagne, Sarah J. Mitchell, Julie A. Mattison, Yun Chen, Justine Bacchetta, Pawel Szulc, Richard N. Kitsis, Rafael De Cabo, Richard A. Friedman, Christopher Torsitano, Timothy E. McGraw, Michelle Puchowicz, Irwin J. Kurland, Gerard Karsenty

Research output: Contribution to journalArticle

104 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1078-1092
Number of pages15
JournalCell Metabolism
Issue number6
StatePublished - Jun 14 2016


ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Mera, P., Laue, K., Ferron, M., Confavreux, C., Wei, J., Galán-Díez, M., Lacampagne, A., Mitchell, S. J., Mattison, J. A., Chen, Y., Bacchetta, J., Szulc, P., Kitsis, R. N., De Cabo, R., Friedman, R. A., Torsitano, C., McGraw, T. E., Puchowicz, M., Kurland, I. J., & Karsenty, G. (2016). Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise. Cell Metabolism, 23(6), 1078-1092. https://doi.org/10.1016/j.cmet.2016.05.004