Effect of short-term fasting and refeeding on transcriptional regulation of metabolic genes in human skeletal muscle.
During short-term fasting, substrate utilization in skeletal muscle shifts from predominantly carbohydrate to fat as a means of conserving glucose. To examine the potential influence of short-term fasting and refeeding on transcriptional regulation in skeletal muscle, muscle biopsies were obtained from nine male subjects at rest, after 20 h of fasting, and 1 h after consuming either a high-carbohydrate (CHO trial) or a low-carbohydrate (FAT trial) meal. Fasting induced an increase in transcription of the pyruvate dehydrogenase kinase 4 (PDK4) (10-fold), lipoprotein lipase (LPL) ( approximately 2-fold), uncoupling protein 3 (UCP3) ( approximately 5-fold), and carnitine palmitoyltransferase I (CPT I) ( approximately 2.5-fold) genes. Surprisingly, transcription of PDK4 and LPL increased further in response to refeeding (both trials) to more than 50-fold and 6- to 10-fold, respectively, over prefasting levels. However, responses varied among subjects with two subjects in particular displaying far greater activation of PDK4 (>100-fold) and LPL (>20-fold) than the other subjects (mean approximately 8-fold and approximately 2-fold, respectively). Transcription of UCP3 decreased to basal levels after the CHO meal but remained elevated after the FAT meal, whereas CPT I remained elevated after both refeeding meals. The present findings demonstrate that short-term fasting/refeeding in humans alters the transcription of several genes in skeletal muscle related to lipid metabolism. Marked heterogeneity in the transcriptional response to the fasting/refeeding protocol suggests that individual differences in genetic profile may play an important role in adaptive molecular responses to metabolic challenges.
Pilegaard
Henriette
H
Copenhagen Muscle Research Centre, Copenhagen, Denmark.
Saltin
Bengt
B
Neufer
P Darrell
PD
D000328:Adult; D001706:Biopsy; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D005215:Fasting; D005502:Food; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels; D007527:Isoenzymes / Q000235:genetics; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D004040:Dietary Carbohydrates; D007473:Ion Channels; D007527:Isoenzymes; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; D002334:Carnitine O-Palmitoyltransferase; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D008071:Lipoprotein Lipase