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

被引：348

作者：

Mera, Paula ^{[1
]}

Laue, Kathrin ^{[1
]}

Ferron, Mathieu ^{[1
,12
]}

Confavreux, Cyril ^{[2
]}

Wei, Jianwen ^{[1
]}

Galan-Diez, Marta ^{[3
]}

Lacampagne, Alain ^{[4
]}

Mitchell, Sarah J. ^{[5
]}

Mattison, Julie A. ^{[5
]}

Chen, Yun ^{[6
,7
]}

Bacchetta, Justine ^{[2
]}

Szulc, Pawel ^{[2
]}

Kitsis, Richard N. ^{[6
,7
]}

de Cabo, Rafael ^{[5
]}

Friedman, Richard A. ^{[8
]}

Torsitano, Christopher ^{[9
]}

McGraw, Timothy E. ^{[9
]}

Puchowicz, Michelle ^{[10
]}

Kurland, Irwin ^{[11
]}

Karsenty, Gerard ^{[1
]}

机构：

[1] Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY 10032 USA

[2] Univ Lyon, Hosp Civils Lyon, INSERM, UMR1033, F-69003 Lyon, France

[3] Columbia Univ, Med Ctr, Dept Physiol & Cellular Biophys, New York, NY 10032 USA

[4] Univ Montpellier, CHRU Montpellier, CNRS, INSERM,UMR 9214,U1046, F-34295 Montpellier 5, France

[5] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA

[6] Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Dept Med Cardiol, 1300 Morris Pk Ave, Bronx, NY 10461 USA

[7] Yeshiva Univ Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Bronx, NY 10461 USA

[8] Columbia Univ, Med Ctr, Dept Biomed Informat, New York, NY 10032 USA

[9] Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10065 USA

[10] Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH 44106 USA

[11] Yeshiva Univ Albert Einstein Coll Med, Dept Med, 1300 Morris Pk Ave, Bronx, NY 10461 USA

[12] Inst Rech Clin Montreal, Integrat & Mol Physiol Res Unit, Montreal, PQ H2W 1R7, Canada

来源：

CELL METABOLISM | 2016年 / 23卷 / 06期

关键词：

SKELETAL-MUSCLE CONTRACTION; AMPK PHOSPHORYLATION; ENERGY-METABOLISM; INSULIN; GLUCOSE; INTERLEUKIN-6; DISTINCT; BONE; MECHANISMS; EXPRESSION;

D O I：

10.1016/j.cmet.2016.05.004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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-tomuscle feedforward endocrine axis that favors adaptation to exercise and can reverse the age-induced decline in exercise capacity.

引用

页码：1078 / 1092

页数：15

共 47 条

[1]

Muscle as a "Mediator" of Systemic Metabolism [J].