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- Title
LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle.
- Authors
Hirotaka Araki; Shinjiro Hino; Kotaro Anan; Kanji Kuribayashi; Kan Etoh; Daiki Seko; Ryuta Takase; Kensaku Kohrogi; Yuko Hino; Yusuke Ono; Eiichi Araki; Mitsuyoshi Nakao
- Abstract
Skeletal muscle exhibits remarkable plasticity in response to environmental cues, with stress-dependent effects on the fast-twitch and slow-twitch fibers. Although stress-induced gene expression underlies environmental adaptation, it is unclear how transcriptional and epigenetic factors regulate fiber type-specific responses in the muscle. Here, we show that flavin-dependent lysine-specific demethylase-1 (LSD1) differentially controls responses to glucocorticoid and exercise in postnatal skeletal muscle. Using skeletal muscle-specific LSD1-knockout mice and in vitro approaches, we found that LSD1 loss exacerbated glucocorticoid-induced atrophy in the fast fiber-dominant muscles, with reduced nuclear retention of Foxk1, an anti-autophagic transcription factor. Furthermore, LSD1 depletion enhanced endurance exercise-induced hypertrophy in the slow fiber-dominant muscles, by induced expression of ERR?, a transcription factor that promotes oxidative metabolism genes. Thus, LSD1 serves as an 'epigenetic barrier' that optimizes fiber type-specific responses and muscle mass under the stress conditions. Our results uncover that LSD1 modulators provide emerging therapeutic and preventive strategies against stress-induced myopathies such as sarcopenia, cachexia, and disuse atrophy.
- Subjects
SKELETAL muscle; GENE expression; FIBERS; TRANSCRIPTION factors; MUSCLE mass; CACHEXIA; ATROPHY; SARCOPENIA
- Publication
eLife, 2023, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.84618