Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise.
Endurance exercise improves insulin sensitivity and increases fat oxidation, which are partly facilitated by the induction of metabolic transcription factors. Next to exercise, increased levels of FFA's also increase the gene expression of transcription factors, hence making it difficult to discern the effects from contractile signals produced during exercise, from those produced by increased circulatory FFA's. We aimed to investigate, in human skeletal muscle, whether acute exercise affects gene expression of metabolic transcriptional co-activators and transcription factors, including PGC-1alpha, PRC, PPARalpha, beta/delta, and gamma and RXR, SREBP-1c and FKHR, and to discern the effect of exercise per se from those of elevated levels of FFA. Two hours of endurance exercise was performed either in the fasted state, or following carbohydrate ingestion prior to and during exercise, thereby blunting the fasting-induced increase in FA availability and oxidation. Of the genes measured, PGC-1alpha and PRC mRNA increased immediately after, while PPARbeta/delta and FKHR mRNA increased 1-4 h after exercise, irrespective of the increases in FFA's. Our results suggest that the induction in vivo of metabolic transcription factors implicated in mitochondrial biogenesis are under the control of inherent signals, (PGC-1alpha, PRC), while those implicated in substrate selection are under the control of associated signals (PPARbeta/delta, FKHR) stimulated from the contracting skeletal muscle that are independent of circulating FFA levels.
Russell
Aaron P
AP
Clinique Romande de Réadaptation SUVA Care, Sion, Switzerland. aaron.russell@crr-suva.ch
Hesselink
Matthijs K C
MK
Lo
Sing Kai
SK
Schrauwen
Patrick
P
D004040:Dietary Carbohydrates / Q000008:administration & dosage; D015444:Exercise / Q000502:physiology*; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D007700:Kinetics; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000235:genetics; D048068:PPAR-beta / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010807:Physical Endurance / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D004040:Dietary Carbohydrates; C085126:FOXO1 protein, human; D005230:Fatty Acids, Nonesterified; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins; D047495:PPAR gamma; D048068:PPAR-beta; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1