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 Kurland; Gerard Karsenty

doi:10.1016/j.cmet.2016.05.004

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 Kurland, Gerard Karsenty

Medicine

Research output: Contribution to journal › Article › peer-review

272 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	1078-1092
Number of pages	15
Journal	Cell metabolism
Volume	23
Issue number	6
DOIs	https://doi.org/10.1016/j.cmet.2016.05.004
State	Published - Jun 14 2016

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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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., & 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

Mera, P, Laue, K, Ferron, M, Confavreux, C, Wei, J, Galán-Díez, M, Lacampagne, A, Mitchell, SJ, Mattison, JA, Chen, Y, Bacchetta, J, Szulc, P, Kitsis, RN, De Cabo, R, Friedman, RA, Torsitano, C, McGraw, TE, Puchowicz, M, Kurland, I & Karsenty, G 2016, 'Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise', Cell metabolism, vol. 23, no. 6, pp. 1078-1092. https://doi.org/10.1016/j.cmet.2016.05.004

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title = "Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise",

abstract = "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.",

author = "Paula Mera and Kathrin Laue and Mathieu Ferron and Cyril Confavreux and Jianwen Wei and Marta Gal{\'a}n-D{\'i}ez and Alain Lacampagne and Mitchell, {Sarah J.} and Mattison, {Julie A.} and Yun Chen and Justine Bacchetta and Pawel Szulc and Kitsis, {Richard N.} and {De Cabo}, Rafael and Friedman, {Richard A.} and Christopher Torsitano and McGraw, {Timothy E.} and Michelle Puchowicz and Irwin Kurland and Gerard Karsenty",

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AU - Wei, Jianwen

AU - Galán-Díez, Marta

AU - Lacampagne, Alain

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AU - Mattison, Julie A.

AU - Chen, Yun

AU - Bacchetta, Justine

AU - Szulc, Pawel

AU - Kitsis, Richard N.

AU - De Cabo, Rafael

AU - Friedman, Richard A.

AU - Torsitano, Christopher

AU - McGraw, Timothy E.

AU - Puchowicz, Michelle

AU - Kurland, Irwin

AU - Karsenty, Gerard

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N2 - 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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Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise

Abstract

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