Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity.
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(-/-)β(f/f/MLC-Cre) mice) were generated and characterized. PGC-1α(-/-)β(f/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(-/-)β(f/f/MLC-Cre) mice. Moreover, insulin sensitivity and glucose tolerance were not altered in the PGC-1α(-/-)β(f/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.
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Christoph
C
Zechner
Ling
L
Lai
Juliet F
JF
Zechner
Tuoyu
T
Geng
Zhen
Z
Yan
John W
JW
Rumsey
Deanna
D
Collia
Zhouji
Z
Chen
David F
DF
Wozniak
Teresa C
TC
Leone
Daniel P
DP
Kelly
D000704:Analysis of Variance; D000818:Animals; D020869:Gene Expression Profiling; D005951:Glucose Tolerance Test; D007333:Insulin Resistance / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000172:deficiency* / Q000378:metabolism
D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1