Details

Autor(en) / Beteiligte

• Araki, Hirotaka
• Hino, Shinjiro
• Anan, Kotaro
• Kuribayashi, Kanji
• Etoh, Kan
• Seko, Daiki
• Takase, Ryuta
• Kohrogi, Kensaku
• Hino, Yuko
• Ono, Yusuke
• Araki, Eiichi
• Nakao, Mitsuyoshi

Titel

LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle

Ist Teil von

• eLife, 2023-01, Vol.12

Ort / Verlag

England: eLife Science Publications, Ltd

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 ERRγ, 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.