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Muscle-derived interleukin 6 increases exercise capacity by signaling in osteoblasts
Subrata Chowdhury1, Logan Schulz1, Biagio Palmisano1
1Department of Genetics and Development, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
The Journal of Clinical Investigation
|February 21, 2020
Summary
Exercise capacity relies on a muscle-bone-muscle axis. Muscle-derived interleukin-6 (IL-6) signals to bone cells, promoting osteocalcin release, which enhances nutrient uptake for muscle function during exercise.
Area of Science:
- Endocrinology
- Exercise Physiology
- Molecular Biology
Background:
- Exercise capacity is crucial for health, but its regulation remains incompletely understood.
- Interleukin-6 (IL-6) increases during exercise and enhances performance, yet its source and mechanism are unclear.
- Understanding IL-6's role is vital for optimizing exercise benefits.
Purpose of the Study:
- To identify the cellular origin of circulating IL-6 during exercise.
- To elucidate the mechanism by which IL-6 enhances exercise capacity.
- To investigate the interplay between IL-6, osteocalcin, and muscle function.
Main Methods:
- Genetic manipulation in mice to ablate IL-6 receptors in specific cell types (osteoblasts).
- Analysis of exercise capacity in genetically modified mice and wild-type controls.
- Measurement of circulating IL-6 and osteocalcin levels.
- Assessment of nutrient uptake and catabolism in muscle fibers.
Main Results:
- The majority of circulating IL-6 during exercise originates from skeletal muscle.
- IL-6 enhances exercise capacity by signaling through osteoblasts, promoting osteoclast differentiation and osteocalcin release.
- Mice lacking IL-6 receptors in osteoblasts showed reduced exercise capacity, correctable by osteocalcin.
- Muscle-derived IL-6 (mIL-6) facilitates nutrient uptake in muscle via an osteocalcin-dependent pathway.
- This muscle-bone-muscle endocrine axis is conserved in humans.
Conclusions:
- A novel muscle-bone-muscle endocrine axis is essential for regulating exercise capacity.
- Interleukin-6 (IL-6) from muscle acts on bone to release osteocalcin, which in turn supports muscle function.
- This pathway highlights a critical crosstalk between muscle and bone metabolism during physical activity.
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