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Proc Natl Acad Sci U S A DOI:10.1073/pnas.1115813109

Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction.

Publication TypeJournal Article
Year of Publication2012
AuthorsFinley, LWS, Lee, J, Souza, A, Desquiret-Dumas, V, Bullock, K, Rowe, GC, Procaccio, V, Clish, CB, Arany, Z, Haigis, MC
JournalProc Natl Acad Sci U S A
Volume109
Issue8
Pages2931-6
Date Published2012 Feb 21
ISSN1091-6490
KeywordsAnimals, Caloric Restriction, Genes, Mitochondrial, Homeostasis, Metabolomics, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Muscle Fibers, Skeletal, Muscle, Skeletal, Oxidation-Reduction, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Trans-Activators, Transcription Factors, Transcription, Genetic
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-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.

URLhttp://www.pnas.org/cgi/pmidlookup?view=long&pmid=22308395
DOI10.1073/pnas.1115813109
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22308395?dopt=Abstract

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID22308395
PubMed Central IDPMC3286952
Grant ListR01 AG032375 / AG / NIA NIH HHS / United States
AG032375 / AG / NIA NIH HHS / United States