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

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 fib...

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Autores principales: Araki, Hirotaka, Hino, Shinjiro, Anan, Kotaro, Kuribayashi, Kanji, Etoh, Kan, Seko, Daiki, Takase, Ryuta, Kohrogi, Kensaku, Hino, Yuko, Ono, Yusuke, Araki, Eiichi, Nakao, Mitsuyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9876571/
https://www.ncbi.nlm.nih.gov/pubmed/36695573
http://dx.doi.org/10.7554/eLife.84618
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author Araki, Hirotaka
Hino, Shinjiro
Anan, Kotaro
Kuribayashi, Kanji
Etoh, Kan
Seko, Daiki
Takase, Ryuta
Kohrogi, Kensaku
Hino, Yuko
Ono, Yusuke
Araki, Eiichi
Nakao, Mitsuyoshi
author_facet Araki, Hirotaka
Hino, Shinjiro
Anan, Kotaro
Kuribayashi, Kanji
Etoh, Kan
Seko, Daiki
Takase, Ryuta
Kohrogi, Kensaku
Hino, Yuko
Ono, Yusuke
Araki, Eiichi
Nakao, Mitsuyoshi
author_sort Araki, Hirotaka
collection PubMed
description 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.
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spelling pubmed-98765712023-01-26 LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle Araki, Hirotaka Hino, Shinjiro Anan, Kotaro Kuribayashi, Kanji Etoh, Kan Seko, Daiki Takase, Ryuta Kohrogi, Kensaku Hino, Yuko Ono, Yusuke Araki, Eiichi Nakao, Mitsuyoshi eLife Cell Biology 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. eLife Sciences Publications, Ltd 2023-01-25 /pmc/articles/PMC9876571/ /pubmed/36695573 http://dx.doi.org/10.7554/eLife.84618 Text en © 2023, Araki et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Araki, Hirotaka
Hino, Shinjiro
Anan, Kotaro
Kuribayashi, Kanji
Etoh, Kan
Seko, Daiki
Takase, Ryuta
Kohrogi, Kensaku
Hino, Yuko
Ono, Yusuke
Araki, Eiichi
Nakao, Mitsuyoshi
LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle
title LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle
title_full LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle
title_fullStr LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle
title_full_unstemmed LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle
title_short LSD1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle
title_sort lsd1 defines the fiber type-selective responsiveness to environmental stress in skeletal muscle
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9876571/
https://www.ncbi.nlm.nih.gov/pubmed/36695573
http://dx.doi.org/10.7554/eLife.84618
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