Given the numerous health benefits of exercise, understanding how exercise capacity is regulated is a question of paramount importance. Circulating interleukin 6 (IL-6) levels surge during exercise and IL-6 favors exercise capacity. However, neither the cellular origin of circulating IL-6 during exercise nor the means by which this cytokine enhances exercise capacity has been formally established yet. Here we show through genetic means that the majority of circulating IL-6 detectable during exercise originates from muscle and that to increase exercise capacity, IL-6 must signal in osteoblasts to favor osteoclast differentiation and the release of bioactive osteocalcin in the general circulation. This explains why mice lacking the IL-6 receptor only in osteoblasts exhibit a deficit in exercise capacity of similar severity to the one seen in mice lacking muscle-derived IL-6 (mIL-6), and why this deficit is correctable by osteocalcin but not by IL-6. Furthermore, in agreement with the notion that IL-6 acts through osteocalcin, we demonstrate that mIL-6 promotes nutrient uptake and catabolism into myofibers during exercise in an osteocalcin-dependent manner. Finally, we show that the crosstalk between osteocalcin and IL-6 is conserved between rodents and humans. This study provides evidence that a muscle-bone-muscle endocrine axis is necessary to increase muscle function during exercise in rodents and humans.
Muscle-derived interleukin 6 increases exercise capacity by signaling in osteoblasts / Chowdhury, Subrata; Schulz, Logan; Palmisano, Biagio; Singh, Parminder; Berger, Julian M.; Yadav, Vijay K.; Mera, Paula; Ellingsgaard, Helga; Hidalgo, Juan; Brüning, Jens; Karsenty, Gerard. - In: THE JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0021-9738. - 130:6(2020), pp. 2888-2902. [10.1172/JCI133572]
Muscle-derived interleukin 6 increases exercise capacity by signaling in osteoblasts
Palmisano, Biagio;
2020
Abstract
Given the numerous health benefits of exercise, understanding how exercise capacity is regulated is a question of paramount importance. Circulating interleukin 6 (IL-6) levels surge during exercise and IL-6 favors exercise capacity. However, neither the cellular origin of circulating IL-6 during exercise nor the means by which this cytokine enhances exercise capacity has been formally established yet. Here we show through genetic means that the majority of circulating IL-6 detectable during exercise originates from muscle and that to increase exercise capacity, IL-6 must signal in osteoblasts to favor osteoclast differentiation and the release of bioactive osteocalcin in the general circulation. This explains why mice lacking the IL-6 receptor only in osteoblasts exhibit a deficit in exercise capacity of similar severity to the one seen in mice lacking muscle-derived IL-6 (mIL-6), and why this deficit is correctable by osteocalcin but not by IL-6. Furthermore, in agreement with the notion that IL-6 acts through osteocalcin, we demonstrate that mIL-6 promotes nutrient uptake and catabolism into myofibers during exercise in an osteocalcin-dependent manner. Finally, we show that the crosstalk between osteocalcin and IL-6 is conserved between rodents and humans. This study provides evidence that a muscle-bone-muscle endocrine axis is necessary to increase muscle function during exercise in rodents and humans.File | Dimensione | Formato | |
---|---|---|---|
Palmisano_Muscle-derived_1-6.pdf
accesso aperto
Note: https://www.jci.org/articles/view/133572
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Tutti i diritti riservati (All rights reserved)
Dimensione
6.41 MB
Formato
Adobe PDF
|
6.41 MB | Adobe PDF | |
Palmisano_Muscle-derived_7-12.pdf
accesso aperto
Note: https://www.jci.org/articles/view/133572
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Tutti i diritti riservati (All rights reserved)
Dimensione
3.49 MB
Formato
Adobe PDF
|
3.49 MB | Adobe PDF | |
Palmisano_Muscle-derived_13-16.pdf
accesso aperto
Note: https://www.jci.org/articles/view/133572
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Tutti i diritti riservati (All rights reserved)
Dimensione
1.04 MB
Formato
Adobe PDF
|
1.04 MB | Adobe PDF |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.