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Myonectin protects against skeletal muscle dysfunction in male mice through activation of AMPK/PGC1α pathway

Author

Listed:
  • Yuta Ozaki

    (Nagoya University Graduate School of Medicine)

  • Koji Ohashi

    (Nagoya University Graduate School of Medicine)

  • Naoya Otaka

    (Nagoya University Graduate School of Medicine)

  • Hiroshi Kawanishi

    (Nagoya University Graduate School of Medicine)

  • Tomonobu Takikawa

    (Nagoya University Graduate School of Medicine)

  • Lixin Fang

    (Nagoya University Graduate School of Medicine)

  • Kunihiko Takahara

    (Nagoya University Graduate School of Medicine)

  • Minako Tatsumi

    (Nagoya University Graduate School of Medicine)

  • Sohta Ishihama

    (Nagoya University Graduate School of Medicine)

  • Mikito Takefuji

    (Nagoya University Graduate School of Medicine)

  • Katsuhiro Kato

    (Nagoya University Graduate School of Medicine)

  • Yuuki Shimizu

    (Nagoya University Graduate School of Medicine)

  • Yasuko K. Bando

    (Nagoya University Graduate School of Medicine)

  • Aiko Inoue

    (Nagoya University Graduate School of Medicine)

  • Masafumi Kuzuya

    (Nagoya University Graduate School of Medicine
    Nagoya University Graduate School of Medicine)

  • Shinji Miura

    (University of Shizuoka)

  • Toyoaki Murohara

    (Nagoya University Graduate School of Medicine)

  • Noriyuki Ouchi

    (Nagoya University Graduate School of Medicine)

Abstract

To maintain and restore skeletal muscle mass and function is essential for healthy aging. We have found that myonectin acts as a cardioprotective myokine. Here, we investigate the effect of myonectin on skeletal muscle atrophy in various male mouse models of muscle dysfunction. Disruption of myonectin exacerbates skeletal muscle atrophy in age-associated, sciatic denervation-induced or dexamethasone (DEX)-induced muscle atrophy models. Myonectin deficiency also contributes to exacerbated mitochondrial dysfunction and reduces expression of mitochondrial biogenesis-associated genes including PGC1α in denervated muscle. Myonectin supplementation attenuates denervation-induced muscle atrophy via activation of AMPK. Myonectin also reverses DEX-induced atrophy of cultured myotubes through the AMPK/PGC1α signaling. Furthermore, myonectin treatment suppresses muscle atrophy in senescence-accelerated mouse prone (SAMP) 8 mouse model of accelerated aging or mdx mouse model of Duchenne muscular dystrophy. These data indicate that myonectin can ameliorate skeletal muscle dysfunction through AMPK/PGC1α-dependent mechanisms, suggesting that myonectin could represent a therapeutic target of muscle atrophy.

Suggested Citation

  • Yuta Ozaki & Koji Ohashi & Naoya Otaka & Hiroshi Kawanishi & Tomonobu Takikawa & Lixin Fang & Kunihiko Takahara & Minako Tatsumi & Sohta Ishihama & Mikito Takefuji & Katsuhiro Kato & Yuuki Shimizu & Y, 2023. "Myonectin protects against skeletal muscle dysfunction in male mice through activation of AMPK/PGC1α pathway," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40435-2
    DOI: 10.1038/s41467-023-40435-2
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    References listed on IDEAS

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    1. Stephan Herzig & Fanxin Long & Ulupi S. Jhala & Susan Hedrick & Rebecca Quinn & Anton Bauer & Dorothea Rudolph & Gunther Schutz & Cliff Yoon & Pere Puigserver & Bruce Spiegelman & Marc Montminy, 2001. "Correction: CREB regulates hepatic gluconeogenesis through the coactivator PGC-1," Nature, Nature, vol. 413(6856), pages 652-652, October.
    2. Katsuhiro Kato & Rodrigo Diéguez-Hurtado & Do Young Park & Seon Pyo Hong & Sakiko Kato-Azuma & Susanne Adams & Martin Stehling & Britta Trappmann & Jeffrey L. Wrana & Gou Young Koh & Ralf H. Adams, 2018. "Pulmonary pericytes regulate lung morphogenesis," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    3. Stephan Herzig & Fanxin Long & Ulupi S. Jhala & Susan Hedrick & Rebecca Quinn & Anton Bauer & Dorothea Rudolph & Gunther Schutz & Cliff Yoon & Pere Puigserver & Bruce Spiegelman & Marc Montminy, 2001. "CREB regulates hepatic gluconeogenesis through the coactivator PGC-1," Nature, Nature, vol. 413(6852), pages 179-183, September.
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