Human skeletal muscle macrophages increase following cycle training and are associated with adaptations that may facilitate growth

R. Grace Walton, Kate Kosmac, Jyothi Mula, Christopher S. Fry, Bailey D. Peck, Jason S. Groshong, Brian S. Finlin, Beibei Zhu, Philip A. Kern, Charlotte A. Peterson

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Skeletal muscle macrophages participate in repair and regeneration following injury. However, their role in physiological adaptations to exercise is unexplored. We determined whether endurance exercise training (EET) alters macrophage content and characteristics in response to resistance exercise (RE), and whether macrophages are associated with other exercise adaptations. Subjects provided vastus lateralis biopsies before and after one bout of RE, after 12 weeks of EET (cycling), and after a final bout of RE. M2 macrophages (CD11b+/CD206+) did not increase with RE, but increased in response to EET (P < 0.01). Increases in M2 macrophages were positively correlated with fiber hypertrophy (r = 0.49) and satellite cells (r = 0.47). M2c macrophages (CD206+/CD163+) also increased following EET (P < 0.001), and were associated with fiber hypertrophy (r = 0.64). Gene expression was quantified using NanoString. Following EET, the change in M2 macrophages was positively associated with changes in HGF, IGF1, and extracellular matrix genes. EET decreased expression of IL6 (P < 0.05), C/EBPβ (P < 0.01), and MuRF (P < 0.05), and increased expression of IL-4 (P < 0.01), TNFα (P < 0.01) and the TWEAK receptor FN14 (P < 0.05). The change in FN14 gene expression was inversely associated with changes in C/EBPβ (r = −0.58) and MuRF (r = −0.46) following EET. In cultured human myotubes, siRNA inhibition of FN14 increased expression of C/EBPβ (P < 0.05) and MuRF (P < 0.05). Our data suggest that macrophages contribute to the muscle response to EET, potentially including modulation of TWEAK-FN14 signaling.

Original languageEnglish
Article number969
JournalScientific Reports
Issue number1
StatePublished - Dec 1 2019

Bibliographical note

Funding Information:
The authors would like offer our sincere gratitude to Ms. Samantha Michaelis and Mr. Kyle Polley for counting macrophages. We would also like to thank Ms. Donna Wall and Dr. Kuey Chen of the University of Kentucky Genomics Core Laboratory for assistance with NanoString nCounter processing. We are grateful to Dr. Jeffrey A. Winkles of the University of Maryland for kindly providing FN14 and vector control plasmids. The authors also offer our sincere thanks to the many participants who were a part of this study. This work was supported by the following NIH grants: DK071349 and AG046920 (C.A.P. and P.A.K.); UL1TR001998; P20 GM103527.

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus subject areas

  • General


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