Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction
Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation, and reactive oxygen species (ROS) scavenging in skeletal muscle and other tissues, and these processes are thought to be cri...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences
2012
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| Online Access: | http://hdl.handle.net/1721.1/72529 |
| _version_ | 1811079092552859648 |
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| author | Finley, Lydia W. S. Lee, Jaewon Souza, Amanda Desquiret-Dumas, Valérie Bullock, Kevin Rowe, Glenn C. Procaccio, Vincent Clish, Clary Arany, Zoltan Haigis, Marcia C. |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Finley, Lydia W. S. Lee, Jaewon Souza, Amanda Desquiret-Dumas, Valérie Bullock, Kevin Rowe, Glenn C. Procaccio, Vincent Clish, Clary Arany, Zoltan Haigis, Marcia C. |
| author_sort | Finley, Lydia W. S. |
| collection | MIT |
| description | Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation, and reactive oxygen species (ROS) scavenging in skeletal muscle and other tissues, and these processes are thought to be critical to the benefits of CR. PGC-1α is a transcriptional coactivator that regulates mitochondrial function and is induced by CR. Consequently, many of the mitochondrial and metabolic benefits of CR are attributed to increased PGC-1α activity. To test this model, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle PGC-1α (MKO). Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1α is dispensable for the whole-body benefits of CR. In contrast, gene expression profiling and electron microscopy (EM) demonstrated that PGC-1α is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1α is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1α nor mitochondrial biogenesis in skeletal muscle are required for the whole-body metabolic benefits of CR. |
| first_indexed | 2024-09-23T11:09:55Z |
| format | Article |
| id | mit-1721.1/72529 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:09:55Z |
| publishDate | 2012 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/725292022-09-27T17:34:28Z Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction Finley, Lydia W. S. Lee, Jaewon Souza, Amanda Desquiret-Dumas, Valérie Bullock, Kevin Rowe, Glenn C. Procaccio, Vincent Clish, Clary Arany, Zoltan Haigis, Marcia C. Koch Institute for Integrative Cancer Research at MIT Souza, Amanda Souza, Amanda Clish, Clary Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation, and reactive oxygen species (ROS) scavenging in skeletal muscle and other tissues, and these processes are thought to be critical to the benefits of CR. PGC-1α is a transcriptional coactivator that regulates mitochondrial function and is induced by CR. Consequently, many of the mitochondrial and metabolic benefits of CR are attributed to increased PGC-1α activity. To test this model, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle PGC-1α (MKO). Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1α is dispensable for the whole-body benefits of CR. In contrast, gene expression profiling and electron microscopy (EM) demonstrated that PGC-1α is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1α is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1α nor mitochondrial biogenesis in skeletal muscle are required for the whole-body metabolic benefits of CR. 2012-09-05T18:10:45Z 2012-09-05T18:10:45Z 2012-02 2011-10 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/72529 Finley, L. W. S. et al. “Skeletal Muscle Transcriptional Coactivator PGC-1 Mediates Mitochondrial, but Not Metabolic, Changes During Calorie Restriction.” Proceedings of the National Academy of Sciences 109.8 (2012): 2931–2936. Copyright ©2012 by the National Academy of Sciences en_US http://dx.doi.org/10.1073/pnas.1115813109 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Finley, Lydia W. S. Lee, Jaewon Souza, Amanda Desquiret-Dumas, Valérie Bullock, Kevin Rowe, Glenn C. Procaccio, Vincent Clish, Clary Arany, Zoltan Haigis, Marcia C. Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction |
| title | Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction |
| title_full | Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction |
| title_fullStr | Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction |
| title_full_unstemmed | Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction |
| title_short | Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction |
| title_sort | skeletal muscle transcriptional coactivator pgc 1α mediates mitochondrial but not metabolic changes during calorie restriction |
| url | http://hdl.handle.net/1721.1/72529 |
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