Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise Academic Article uri icon


MeSH Major

  • Adipocytes
  • Glucose Transporter Type 4
  • Insulin
  • Insulin Resistance
  • Liver
  • rab GTP-Binding Proteins


  • 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.

publication date

  • June 14, 2016



  • Academic Article



  • eng

PubMed Central ID

  • PMC4910629

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2016.05.004

PubMed ID

  • 27304508

Additional Document Info

start page

  • 1078

end page

  • 92


  • 23


  • 6