Journal article
Skeletal muscle transcriptional coactivator PGC-1 alpha mediates mitochondrial, but not metabolic, changes during calorie restriction
Proceedings of the National Academy of Sciences - PNAS, Vol.109(8), pp.2931-2936
02/21/2012
DOI: 10.1073/pnas.1115813109
PMCID: PMC3286952
PMID: 22308395
Abstract
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-1 alpha 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-1 alpha activity. To test this model, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle PGC-1 alpha (MKO). Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1 alpha is dispensable for the whole-body benefits of CR. In contrast, gene expression profiling and electron microscopy (EM) demonstrated that PGC-1 alpha is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1 alpha is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1 alpha nor mitochondrial biogenesis in skeletal muscle are required for the whole-body metabolic benefits of CR.
Details
- Title: Subtitle
- Skeletal muscle transcriptional coactivator PGC-1 alpha mediates mitochondrial, but not metabolic, changes during calorie restriction
- Creators
- Lydia W. S. Finley - Harvard UniversityJaewon Lee - Harvard UniversityAmanda Souza - Broad InstituteValerie Desquiret-Dumas - Centre National de la Recherche ScientifiqueKevin Bullock - Broad InstituteGlenn C. Rowe - Beth Israel Deaconess Medical CenterVincent Procaccio - Centre National de la Recherche ScientifiqueClary B. Clish - Broad InstituteZoltan Arany - Beth Israel Deaconess Medical CenterMarcia C. Haigis - Harvard University
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.109(8), pp.2931-2936
- DOI
- 10.1073/pnas.1115813109
- PMID
- 22308395
- PMCID
- PMC3286952
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- Natl Acad Sciences
- Number of pages
- 6
- Grant note
- Smith Family Foundation National Science Foundation; National Science Foundation (NSF) National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Ellison Medical Foundation; Lawrence Ellison Foundation AG032375 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Glenn Foundation for Medical Research R01AG032375 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA)
- Language
- English
- Date published
- 02/21/2012
- Academic Unit
- Surgery
- Record Identifier
- 9985240892202771
Metrics
1 Record Views