Transcriptional modulation of mitochondria biogenesis pathway at and above critical speed in mice.
High- or moderate-intensity endurance training leads to mitochondrial biogenesis via the peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α)/mitochondrial transcription factor A (Tfam) signaling pathway. Although this pathway is stimulated during acute exercise, the relationship between its activity and the intensity of the exercise has not been characterized. In animal studies, individualized running speeds have not previously been assessed. Here, we sought to determine whether this pathway was modulated after a bout of exhaustive exercise at different relative intensities (at and over critical speed (CS)). Our starting hypotheses were that (i) exercise-induced overexpression of PGC-1α in skeletal muscle falls at intensities above CS, and (ii) transcriptional activity of the mitochondrial biogenesis signaling cascade is intensity-sensitive at and above CS. To test these hypothesis, male Friend Virus B-Type mice were divided into a control group and three exercise groups (exercising at CS, peak velocity (vPeak) and 150 % CS, respectively). mRNA expression levels for genes involved in mitochondrial biogenesis signaling were analyzed in the quadriceps muscle. PGC-1α was overexpressed at all exercise intensities. We also identified that, PGC-1α mRNA expression was negatively correlated with exercise intensity and blood lactate levels but not with maximal oxygen uptake, vPeak, or CS. Expression of the PGC-1α co-activator peroxisome proliferator-activated receptor β was negatively correlated with the exercise intensity. In contrast, expression levels of Tfam were dissociated from exercise intensity. Our data indicate that at the intensities used in endurance training, the expression of mitochondrial biogenesis genes is finely modulated by the relative intensity of exhaustive exercise.
UBIAE, INSERM U902, Université Evry-Val d'Essonne, Bd Francois Mitterrand, Batiment Maupertuis, 91025, Evry, France, laurence.hamard@inserm.fr.
L
L
Mille-Hamard
C
C
Breuneval
A S
AS
Rousseau
P
P
Grimaldi
V L
VL
Billat
D000818:Animals; D053898:Biosynthetic Pathways / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006609:High Mobility Group Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008931:Mitochondria, Muscle / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D048068:PPAR-beta / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D048068:PPAR-beta; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; C081930:Tfam protein, mouse; D014157:Transcription Factors; D010100:Oxygen