Neutrophils Provide a Favorable IL-1-Mediated Immunometabolic Niche that Primes GLUT4 Translocation and Performance in Skeletal Muscles

Masahiro Tsuchiya, Shigenori Sekiai, Hiroyasu Hatakeyama, Masashi Koide, Chayanit Chaweewannakorn, Fukie Yaoita, Koichi Tan-No, Keiichi Sasaki, Makoto Watanabe, Shunji Sugawara, Yasuo Endo, Eiji Itoi, Yoshihiro Hagiwara, Makoto Kanzaki

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Metabolic immunomodulation involving IL-1 has been investigated for unfavorable metabolic effects, including obesity, but a potentially favorable role for IL-1 remains unclear. Here, we find mechanistic interactions between working skeletal muscles and locally recruited neutrophils expressing IL-1β which supports muscle performance through priming exercise-dependent GLUT4 translocation. Thus, during exercise, both IL-1α/β-deficient and neutrophil-depleted mice similarly exhibit increased fatigability associated with impaired muscle glucose homeostasis due to GLUT4 dysregulation. Deficiency of IL-1-producing neutrophils results in intrinsic abnormalities represented by aberrant Rac1 signaling and irregular GLUT4-storage vesicles, suggesting that these properties are maintained by local IL-1 produced by recruited neutrophils upon exercise, possibly on a daily basis. We propose that neutrophils are highly engaged in skeletal muscle performance via IL-1 regulation, which coordinates favorable inflammatory microenvironments supporting muscle glucose metabolism. Immunometabolic IL-1 action has been investigated under unfavorable conditions such as obesity and insulin resistance, but potential favorable IL-1 actions remain unknown. Tsuchiya et al. reveal mechanistic interactions during exercise between working skeletal muscles and locally recruited neutrophils expressing IL-1β which positively supports muscle performance by priming exercise-dependent GLUT4 translocation.

Original languageEnglish
Pages (from-to)2354-2364
Number of pages11
JournalCell Reports
Volume23
Issue number8
DOIs
Publication statusPublished - 2018 May 22

Keywords

  • Exercise
  • GLUT4
  • Rac1
  • immunometabolism
  • inflammation
  • metabolism
  • myokines

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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