期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 316, 期 5, 页码 E940-E947出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00414.2018
关键词
interleukin-6; metalloproteinase; muscle-derived factors; myokines; physical activity
资金
- Danish Cancer Society
- Lundbeck Foundation
- Copenhagen University
- TrygFonden
- Danish National Research Foundation [DNRF55]
- Danish Council for Strategic Research [09-067009, 09-075724]
IL-6 is secreted from muscles to the circulation during high-intensity and long-duration exercise, where muscle-derived IL-6 works as an energy sensor to increase release of energy substrates from liver and adipose tissues. We investigated the mechanism involved in the exercise-mediated surge in IL-6 during exercise. Using interval-based cycling in healthy young men, swimming exercise in mice, and electrical stimulation of primary human muscle cells, we explored the role of lactate production in muscular IL-6 release during exercise. First, we observed a tight correlation between lactate production and IL-6 release during both strenuous bicycling and electrically stimulated muscle cell cultures. In mice, intramuscular injection of lactate mimicked the exercise-dependent release of IL-6, and pH buffering of lactate production during exercise attenuated IL-6 secretion. Next, we used in vivo bioimaging to demonstrate that intrinsic intramuscular proteases were activated in mice during swimming, and that blockade of protease activity blunted swimming-induced IL-6 release in mice. Last, intramuscular injection of the protease hyaluronidase resulted in dramatic increases in serum IL-6 in mice. and immunohistochemical analyses showed that intramuscular lactate and hyaluronidase injections led to release of IL-6-containing intratnyocellular vesicles. We identified a pool of IL-6 located within vesicles of skeletal muscle fibers. which could be readily secreted upon protease activity. This protease-dependent release of IL-6 was initiated by lactate production, linking training intensity and lactate production to IL-6 release during strenuous exercise.
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