Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise.
In skeletal muscle of humans, transcription of several metabolic genes is transiently induced during recovery from exercise when no food is consumed. To determine the potential influence of substrate availability on the transcriptional regulation of metabolic genes during recovery from exercise, 9 male subjects (aged 22-27) completed 75 minutes of cycling exercise at 75% Vo2 max on 2 occasions, consuming either a high-carbohydrate (HC) or low-carbohydrate (LC) diet during the subsequent 24 hours of recovery. Nuclei were isolated and tissue frozen from vastus lateralis muscle biopsies obtained before exercise and 2, 5, 8, and 24 hours after exercise. Muscle glycogen was restored to near resting levels within 5 hours in the HC trial, but remained depressed through 24 hours in the LC trial. During the 2- to 8-hour recovery period, leg glucose uptake was 5- to 15-fold higher with HC ingestion, whereas arterial plasma free fatty acid levels were approximately 3- to 7-fold higher with LC ingestion. Exercise increased (P < .05) transcription and/or mRNA content of the pyruvate dehydrogenase kinase 4, uncoupling protein 3, lipoprotein lipase, carnitine palmitoyltransferase I, hexokinase II, peroxisome proliferator activated receptor gamma coactivator-1 alpha, and peroxisome proliferator activated receptor alpha. Providing HC during recovery reversed the activation of pyruvate dehydrogenase kinase 4, uncoupling protein 3, lipoprotein lipase, and carnitine palmitoyltransferase I within 5 to 8 hours after exercise, whereas providing LC during recovery elicited a sustained/enhanced increase in activation of these genes through 8 to 24 hours of recovery. These findings provide evidence that factors associated with substrate availability and/or cellular metabolic recovery (eg, muscle glycogen restoration) influence the transcriptional regulation of metabolic genes in skeletal muscle of humans during recovery from exercise.
Pilegaard
Henriette
H
Copenhagen Muscle Research Centre, University of Copenhagen, Copenhagen, Denmark.
Osada
Takuya
T
Andersen
Lisbeth T
LT
Helge
Jørn W
JW
Saltin
Bengt
B
Neufer
P Darrell
PD
D000328:Adult; D018955:CD36 Antigens / Q000235:genetics; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics; D006593:Hexokinase / Q000235:genetics; D006801:Humans; D007473:Ion Channels; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D024101:Mitochondrial Proteins; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000201:enzymology / Q000502:physiology*; D047493:PPAR alpha / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D005082:Physical Exertion / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020127:Recovery of Function / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology; D000071247:Uncoupling Protein 3
D018955:CD36 Antigens; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D051275:Glucose Transporter Type 4; D006360:Heat-Shock Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D047493:PPAR alpha; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; C495692:SLC2A4 protein, human; D014157:Transcription Factors; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; D006003:Glycogen; D002334:Carnitine O-Palmitoyltransferase; D006006:Glycogen Synthase; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D006593:Hexokinase; D008071:Lipoprotein Lipase