The myokine meteorin-like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKα2

Jung Ok Lee, Won Seok Byun, Min Ju Kang, Jeong Ah Han, Jiyoung Moon, Min Jeong Shin, Ho Jun Lee, Ji Hyung Chung, Jin Seok Lee, Chang Gue Son, Kwon Ho Song, Tae Woo Kim, Eun Soo Lee, Hong Min Kim, Choon Hee Chung, Kevin R.W. Ngoei, Naomi X.Y. Ling, Jonathan S. Oakhill, Sandra Galic, Lisa Murray-SegalBruce E. Kemp, Kyoung Min Kim, Soo Lim, Hyeon Soo Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Meteorin-like (metrnl) is a recently identified adipomyokine that beneficially affects glucose metabolism; however, its underlying mechanism of action is not completely understood. We here show that the level of metrnl increases in vitro under electrical pulse stimulation and in vivo in exercised mice, suggesting that metrnl is secreted during muscle contractions. In addition, metrnl increases glucose uptake via the calcium-dependent AMPKα2 pathway in skeletal muscle cells and increases the phosphorylation of HDAC5, a transcriptional repressor of GLUT4, in an AMPKα2-dependent manner. Phosphorylated HDAC5 interacts with 14-3-3 proteins and sequesters them in the cytoplasm, resulting in the activation of GLUT4 transcription. An intraperitoneal injection of recombinant metrnl improved glucose tolerance in mice with high-fat-diet-induced obesity or type 2 diabetes, but not in AMPK β1β2 muscle-specific null mice. Metrnl improves glucose metabolism via AMPKα2 and is a promising therapeutic candidate for glucose-related diseases such as type 2 diabetes.

Original languageEnglish
Pages (from-to)2087-2104
Number of pages18
JournalFEBS Journal
Volume287
Issue number10
DOIs
Publication statusPublished - 2020 May 1

Keywords

  • AMPK
  • Metrnl
  • adipomyokine
  • glucose uptake
  • type 2 diabetes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Lee, J. O., Byun, W. S., Kang, M. J., Han, J. A., Moon, J., Shin, M. J., Lee, H. J., Chung, J. H., Lee, J. S., Son, C. G., Song, K. H., Kim, T. W., Lee, E. S., Kim, H. M., Chung, C. H., Ngoei, K. R. W., Ling, N. X. Y., Oakhill, J. S., Galic, S., ... Kim, H. S. (2020). The myokine meteorin-like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKα2. FEBS Journal, 287(10), 2087-2104. https://doi.org/10.1111/febs.15301