title: PGC-1αand fasting-induced PDH regulation in mouse skeletal muscle.
abstract: The purpose of the present study was to examine whether lack of skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) affects the switch in substrate utilization from a fed to fasted state and the fasting-induced pyruvate dehydrogenase (PDH) regulation in skeletal muscle. Skeletal muscle-specific PGC-1αknockout (MKO) mice and floxed littermate controls were fed or fasted for 24 h. Fasting reduced PDHa activity, increased phosphorylation of all four known sites on PDH-E1αand increased pyruvate dehydrogenase kinase (PDK4) and sirtuin 3 (SIRT3) protein levels, but did not alter total acetylation of PDH-E1αLack of muscle PGC-1αdid not affect the switch from glucose to fat oxidation in the transition from the fed to fasted state, but was associated with lower and higher respiratory exchange ratio (RER) in the fed and fasted state, respectively. PGC-1αMKO mice had lower skeletal muscle PDH-E1α, PDK1, 2, 4, and pyruvate dehydrogenase phosphatase (PDP1) protein content than controls, but this did not prevent the fasting-induced increase in PDH-E1αphosphorylation in PGC-1αMKO mice. However, lack of skeletal muscle PGC-1αreduced SIRT3 protein content, increased total lysine PDH-E1αacetylation in the fed state, and prevented a fasting-induced increase in SIRT3 protein. In conclusion, skeletal muscle PGC-1αis required for fasting-induced upregulation of skeletal muscle SIRT3 and maintaining high fat oxidation in the fasted state, but is dispensable for preserving the capability to switch substrate during the transition from the fed to the fasted state and for fasting-induced PDH regulation in skeletal muscle.
authors.affiliation: Section for Cell Biology and Physiology, August Krogh Building, Department of Biology, University of Copenhagen, Copenhagen, Denmark hpilegaard@bio.ku.dk.
authors.forename: Anders
authors.initials: A
authors.lastname: Gudiksen
authors.affiliation: Section for Cell Biology and Physiology, August Krogh Building, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henriette
authors.initials: H
authors.lastname: Pilegaard
mesh_terms: D000818:Animals; D005215:Fasting / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism
chemical_list: C000631433:Pdk1 protein, mouse; C000631439:Pdk4 protein, mouse; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex; C525046:Sirt3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D056566:Sirtuin 3
keywords: 
  PDH
  ; Fasting; PGC‐1α; metabolism; skeletal muscle; substrate utilization