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 language | English (US) |
---|---|
Pages (from-to) | 633-642 |
Number of pages | 10 |
Journal | Cell Metabolism |
Volume | 12 |
Issue number | 6 |
DOIs | |
State | Published - Dec 1 2010 |
ASJC Scopus subject areas
- Physiology
- Molecular Biology
- Cell Biology