12606505

pubmed:Citation

3

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.

eng

AIM

MEDLINE

0012-1797

Print

NLM

657-62

pubmed-meshheading:12606505-Adult, pubmed-meshheading:12606505-Biopsy, pubmed-meshheading:12606505-Carnitine O-Palmitoyltransferase, pubmed-meshheading:12606505-Carrier Proteins, pubmed-meshheading:12606505-Dietary Carbohydrates, pubmed-meshheading:12606505-Fasting, pubmed-meshheading:12606505-Food, pubmed-meshheading:12606505-Gene Expression Regulation, pubmed-meshheading:12606505-Humans, pubmed-meshheading:12606505-Ion Channels, pubmed-meshheading:12606505-Isoenzymes, pubmed-meshheading:12606505-Lipid Metabolism, pubmed-meshheading:12606505-Lipoprotein Lipase, pubmed-meshheading:12606505-Male, pubmed-meshheading:12606505-Mitochondrial Proteins, pubmed-meshheading:12606505-Muscle, Skeletal, pubmed-meshheading:12606505-Protein Kinases, pubmed-meshheading:12606505-RNA, Messenger, pubmed-meshheading:12606505-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12606505-Transcription, Genetic

Effect of short-term fasting and refeeding on transcriptional regulation of metabolic genes in human skeletal muscle.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't