Autocrine effects of novel myokines and their endocrine role in the muscle-fat-crosstalk: myokines as a link between exercise and health benefit
Final Report Abstract
Skeletal muscle represents the largest organ in non-obese subjects and is now considered as an active endocrine organ releasing a host of so-called myokines. These myokines are part of a complex multi-organ crosstalk network that mediates communication between muscle, the liver, adipose tissue, the brain and other organs. Recent data suggest that myokines regulated by muscle contraction may play a key role in mediating the healthpromoting effects of regular physical activity. Using a comprehensive protein profiling of conditioned medium derived from primary human skeletal muscle cells more than 500 proteins were identified of which more than 300 proteins are predicted to be secreted. In total, 88 novel myokines were identified and for 48 myokines a regulation by contraction induced by electrical pulse stimulation (EPS) was found. Subsequently, we have validated selected candidates and investigated their regulation by different factors such as differentiation, EPS-induced contraction, and adipocyte-derived peptides as well as auto/paracrine effects. Moreover, using human blood samples we analysed circulating levels of these myokines before and after acute exercise. The most interesting profile was found for the glycoprotein chitinase-3-like protein 1 (CHI3L1) which is elevated in serum of patients with e.g. cardiovascular disease, insulin resistance and type 2 diabetes. We could show that this novel myokine is upregulated by muscle contraction and able to prevent TNFα-induced inflammatory processes by affecting MCP1, IL-8 and IL-6 mRNA expression and secretion. In addition, CHI3L1 treatment blocks TNFα-induced insulin resistance in primary human myotubes. Therefore, we suggest that the novel myokine CHI3L1 inhibits harmful effects of TNFα and may hence represent an autoprotective factor of skeletal muscle tissue that is upregulated by exercise. The results of the project contribute to the understanding of the endocrine function of human myotubes. Secretory proteins are part of a complex physiological network, and they exert different effects under various environmental conditions. Therefore, our current knowledge of contraction-regulated secretory proteins from skeletal muscle and their roles in distinct signaling pathways according to the organ has to be determined in future studies. For novel myokines additional basic research and clinical studies will provide a further understanding in exercise metabolism.
Publications
- Identification and validation of novel contraction-regulated myokines released from primary human skeletal muscle cells. PLOS ONE. 2013 Apr 24;8(4):e62008
Raschke S, Eckardt K, Holven KB, Jensen J, Eckel J
(See online at https://doi.org/10.1371/journal.pone.0062008) - Regulation of follistatin-like protein 1 expression and secretion in primary human skeletal muscle cells. Arch Physiol Biochem. 2013 May;119(2):75-80
Goergens SW, Raschke S, Holven KB, Jensen J, Eckardt K, Eckel J
(See online at https://doi.org/10.3109/13813455.2013.768270) - (2014): Myokines in insulin resistance and type 2 diabetes. Diabetologia, 2014 Mar 28 [Epub ahead of print]
Eckardt K, Görgens SW, Raschke S, Eckel J
(See online at https://doi.org/10.1007/s00125-014-3224-x) - The novel myokine YKL-40 protects skeletal muscle from inflammation and impaired insulin signaling. Biochem J. 2014 Feb 11 [Epub ahead of print]
Goergens SW, Eckardt K, Elsen M, Tennagels N, Eckel J
