The hepatokine TSK maintains myofiber integrity and exercise endurance and contributes to muscle regeneration
Mammalian skeletal muscle contains heterogenous myofibers with different contractile and metabolic properties that sustain muscle mass and endurance capacity. The transcriptional regulators that govern these myofiber gene programs have been elucidated. However, the hormonal cues that direct the spec...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical investigation
2022-02-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.154746 |
| _version_ | 1811334827687804928 |
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| author | Qiuyu Wang Xiaoxue Qiu Tongyu Liu Cheehoon Ahn Jeffrey F. Horowitz Jiandie D. Lin |
| author_facet | Qiuyu Wang Xiaoxue Qiu Tongyu Liu Cheehoon Ahn Jeffrey F. Horowitz Jiandie D. Lin |
| author_sort | Qiuyu Wang |
| collection | DOAJ |
| description | Mammalian skeletal muscle contains heterogenous myofibers with different contractile and metabolic properties that sustain muscle mass and endurance capacity. The transcriptional regulators that govern these myofiber gene programs have been elucidated. However, the hormonal cues that direct the specification of myofiber types and muscle endurance remain largely unknown. Here, we uncover the secreted factor Tsukushi (TSK) as an extracellular signal that is required for maintaining muscle mass, strength, and endurance capacity and that contributes to muscle regeneration. Mice lacking TSK exhibited reduced grip strength and impaired exercise capacity. Muscle transcriptomic analysis revealed that TSK deficiency results in a remarkably selective impairment in the expression of myofibrillar genes, characteristic of slow-twitch muscle fibers, that is associated with abnormal neuromuscular junction formation. AAV-mediated overexpression of TSK failed to rescue these myofiber defects in adult mice, suggesting that the effects of TSK on myofibers are likely restricted to certain developmental stages. Finally, mice lacking TSK exhibited diminished muscle regeneration following cardiotoxin-induced muscle injury. These findings support a crucial role of TSK as a hormonal cue in the regulation of contractile gene expression, endurance capacity, and muscle regeneration. |
| first_indexed | 2024-04-13T17:14:56Z |
| format | Article |
| id | doaj.art-c175c7d6808847a989859f030f33beb0 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-04-13T17:14:56Z |
| publishDate | 2022-02-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-c175c7d6808847a989859f030f33beb02022-12-22T02:38:09ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-02-0174The hepatokine TSK maintains myofiber integrity and exercise endurance and contributes to muscle regenerationQiuyu WangXiaoxue QiuTongyu LiuCheehoon AhnJeffrey F. HorowitzJiandie D. LinMammalian skeletal muscle contains heterogenous myofibers with different contractile and metabolic properties that sustain muscle mass and endurance capacity. The transcriptional regulators that govern these myofiber gene programs have been elucidated. However, the hormonal cues that direct the specification of myofiber types and muscle endurance remain largely unknown. Here, we uncover the secreted factor Tsukushi (TSK) as an extracellular signal that is required for maintaining muscle mass, strength, and endurance capacity and that contributes to muscle regeneration. Mice lacking TSK exhibited reduced grip strength and impaired exercise capacity. Muscle transcriptomic analysis revealed that TSK deficiency results in a remarkably selective impairment in the expression of myofibrillar genes, characteristic of slow-twitch muscle fibers, that is associated with abnormal neuromuscular junction formation. AAV-mediated overexpression of TSK failed to rescue these myofiber defects in adult mice, suggesting that the effects of TSK on myofibers are likely restricted to certain developmental stages. Finally, mice lacking TSK exhibited diminished muscle regeneration following cardiotoxin-induced muscle injury. These findings support a crucial role of TSK as a hormonal cue in the regulation of contractile gene expression, endurance capacity, and muscle regeneration.https://doi.org/10.1172/jci.insight.154746Muscle biology |
| spellingShingle | Qiuyu Wang Xiaoxue Qiu Tongyu Liu Cheehoon Ahn Jeffrey F. Horowitz Jiandie D. Lin The hepatokine TSK maintains myofiber integrity and exercise endurance and contributes to muscle regeneration JCI Insight Muscle biology |
| title | The hepatokine TSK maintains myofiber integrity and exercise endurance and contributes to muscle regeneration |
| title_full | The hepatokine TSK maintains myofiber integrity and exercise endurance and contributes to muscle regeneration |
| title_fullStr | The hepatokine TSK maintains myofiber integrity and exercise endurance and contributes to muscle regeneration |
| title_full_unstemmed | The hepatokine TSK maintains myofiber integrity and exercise endurance and contributes to muscle regeneration |
| title_short | The hepatokine TSK maintains myofiber integrity and exercise endurance and contributes to muscle regeneration |
| title_sort | hepatokine tsk maintains myofiber integrity and exercise endurance and contributes to muscle regeneration |
| topic | Muscle biology |
| url | https://doi.org/10.1172/jci.insight.154746 |
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