Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity

Christoph Zechner, Ling Lai, Juliet F. Zechner, Tuoyu Geng, Zhen Yan, John W. Rumsey, Deanna Collia, Zhouji Chen, David F. Wozniak, Teresa C. Leone, Daniel P. Kelly

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

Abstract

Evidence is emerging that the PGC-1 coactivators serve a critical role in skeletal muscle metabolism, function, and disease. Mice with total PGC-1 deficiency in skeletal muscle (PGC-1α- /-βf/f/MLC-Cre mice) were generated and characterized. PGC-1α-/-βf/f/MLC-Cre mice exhibit a dramatic reduction in exercise performance compared to single PGC-1α- or PGC-1β-deficient mice and wild-type controls. The exercise phenotype of the PGC-1α-/-β f/f/MLC-Cre mice was associated with a marked diminution in muscle oxidative capacity, together with rapid depletion of muscle glycogen stores. In addition, the PGC-1α/β-deficient muscle exhibited mitochondrial structural derangements consistent with fusion/fission and biogenic defects. Surprisingly, the proportion of oxidative muscle fiber types (I, IIa) was not reduced in the PGC-1α-/-βf/f/MLC-Cre mice. Moreover, insulin sensitivity and glucose tolerance were not altered in the PGC-1α-/-βf/f/MLC-Cre mice. Taken together, we conclude that PGC-1 coactivators are necessary for the oxidative and mitochondrial programs of skeletal muscle but are dispensable for fundamental fiber type determination and insulin sensitivity.

Original languageEnglish
Pages (from-to)633-642
Number of pages10
JournalCell metabolism
Volume12
Issue number6
DOIs
StatePublished - Dec 1 2010

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