Mitochondrial glycerol 3‐phosphate dehydrogenase promotes skeletal muscle regeneration
Abstract While adult mammalian skeletal muscle is stable due to its post‐mitotic nature, muscle regeneration is still essential throughout life for maintaining functional fitness. During certain diseases, such as the modern pandemics of obesity and diabetes, the regeneration process becomes impaired...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2018-12-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201809390 |
| _version_ | 1797282298476888064 |
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| author | Xiufei Liu Hua Qu Yi Zheng Qian Liao Linlin Zhang Xiaoyu Liao Xin Xiong Yuren Wang Rui Zhang Hui Wang Qiang Tong Zhenqi Liu Hui Dong Gangyi Yang Zhiming Zhu Jing Xu Hongting Zheng |
| author_facet | Xiufei Liu Hua Qu Yi Zheng Qian Liao Linlin Zhang Xiaoyu Liao Xin Xiong Yuren Wang Rui Zhang Hui Wang Qiang Tong Zhenqi Liu Hui Dong Gangyi Yang Zhiming Zhu Jing Xu Hongting Zheng |
| author_sort | Xiufei Liu |
| collection | DOAJ |
| description | Abstract While adult mammalian skeletal muscle is stable due to its post‐mitotic nature, muscle regeneration is still essential throughout life for maintaining functional fitness. During certain diseases, such as the modern pandemics of obesity and diabetes, the regeneration process becomes impaired, which leads to the loss of muscle function and contributes to the global burden of these diseases. However, the underlying mechanisms of the impairment are not well defined. Here, we identify mGPDH as a critical regulator of skeletal muscle regeneration. Specifically, it regulates myogenic markers and myoblast differentiation by controlling mitochondrial biogenesis via CaMKKβ/AMPK. mGPDH−/− attenuated skeletal muscle regeneration in vitro and in vivo, while mGPDH overexpression ameliorated dystrophic pathology in mdx mice. Moreover, in patients and animal models of obesity and diabetes, mGPDH expression in skeletal muscle was reduced, further suggesting a direct correlation between its abundance and muscular regeneration capability. Rescuing mGPDH expression in obese and diabetic mice led to a significant improvement in their muscle regeneration. Our study provides a potential therapeutic target for skeletal muscle regeneration impairment during obesity and diabetes. |
| first_indexed | 2024-03-07T17:10:49Z |
| format | Article |
| id | doaj.art-785b1769d5ad46dcb0020e2a462f25a1 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T17:10:49Z |
| publishDate | 2018-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-785b1769d5ad46dcb0020e2a462f25a12024-03-03T01:10:59ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-12-011012n/an/a10.15252/emmm.201809390Mitochondrial glycerol 3‐phosphate dehydrogenase promotes skeletal muscle regenerationXiufei Liu0Hua Qu1Yi Zheng2Qian Liao3Linlin Zhang4Xiaoyu Liao5Xin Xiong6Yuren Wang7Rui Zhang8Hui Wang9Qiang Tong10Zhenqi Liu11Hui Dong12Gangyi Yang13Zhiming Zhu14Jing Xu15Hongting Zheng16Translational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaDivision of Endocrinology and Metabolism Department of Internal Medicine University of Virginia Health System Charlottesville VA USADepartment of Gastroenterology Xinqiao Hospital Third Military Medical University Chongqing ChinaDepartment of Endocrinology The Second Affiliated Hospital Chongqing Medical University Chongqing ChinaDepartment of Hypertension and Endocrinology Daping Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaTranslational Research Key Laboratory for Diabetes Department of Endocrinology Xinqiao Hospital Third Military Medical University Chongqing ChinaAbstract While adult mammalian skeletal muscle is stable due to its post‐mitotic nature, muscle regeneration is still essential throughout life for maintaining functional fitness. During certain diseases, such as the modern pandemics of obesity and diabetes, the regeneration process becomes impaired, which leads to the loss of muscle function and contributes to the global burden of these diseases. However, the underlying mechanisms of the impairment are not well defined. Here, we identify mGPDH as a critical regulator of skeletal muscle regeneration. Specifically, it regulates myogenic markers and myoblast differentiation by controlling mitochondrial biogenesis via CaMKKβ/AMPK. mGPDH−/− attenuated skeletal muscle regeneration in vitro and in vivo, while mGPDH overexpression ameliorated dystrophic pathology in mdx mice. Moreover, in patients and animal models of obesity and diabetes, mGPDH expression in skeletal muscle was reduced, further suggesting a direct correlation between its abundance and muscular regeneration capability. Rescuing mGPDH expression in obese and diabetic mice led to a significant improvement in their muscle regeneration. Our study provides a potential therapeutic target for skeletal muscle regeneration impairment during obesity and diabetes.https://doi.org/10.15252/emmm.201809390diabetesmGPDHobesityskeletal muscle regeneration |
| spellingShingle | Xiufei Liu Hua Qu Yi Zheng Qian Liao Linlin Zhang Xiaoyu Liao Xin Xiong Yuren Wang Rui Zhang Hui Wang Qiang Tong Zhenqi Liu Hui Dong Gangyi Yang Zhiming Zhu Jing Xu Hongting Zheng Mitochondrial glycerol 3‐phosphate dehydrogenase promotes skeletal muscle regeneration EMBO Molecular Medicine diabetes mGPDH obesity skeletal muscle regeneration |
| title | Mitochondrial glycerol 3‐phosphate dehydrogenase promotes skeletal muscle regeneration |
| title_full | Mitochondrial glycerol 3‐phosphate dehydrogenase promotes skeletal muscle regeneration |
| title_fullStr | Mitochondrial glycerol 3‐phosphate dehydrogenase promotes skeletal muscle regeneration |
| title_full_unstemmed | Mitochondrial glycerol 3‐phosphate dehydrogenase promotes skeletal muscle regeneration |
| title_short | Mitochondrial glycerol 3‐phosphate dehydrogenase promotes skeletal muscle regeneration |
| title_sort | mitochondrial glycerol 3 phosphate dehydrogenase promotes skeletal muscle regeneration |
| topic | diabetes mGPDH obesity skeletal muscle regeneration |
| url | https://doi.org/10.15252/emmm.201809390 |
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