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. 2015 Apr;467(4):779-88.
doi: 10.1007/s00424-014-1554-7. Epub 2014 Jun 19.

Mitochondrial biogenesis-associated factors underlie the magnitude of response to aerobic endurance training in rats

Affiliations

Mitochondrial biogenesis-associated factors underlie the magnitude of response to aerobic endurance training in rats

Orsolya Marton et al. Pflugers Arch. 2015 Apr.

Abstract

Trainability is important in elite sport and in recreational physical activity, and the wide range for response to training is largely dependent on genotype. In this study, we compare a newly developed rat model system selectively bred for low and high gain in running distance from aerobic training to test whether genetic segregation for trainability associates with differences in factors associated with mitochondrial biogenesis. Low response trainer (LRT) and high response trainer (HRT) rats from generation 11 of artificial selection were trained five times a week, 30 min per day for 3 months at 70 % VO2max to study the mitochondrial molecular background of trainability. As expected, we found significant differential for the gain in running distance between LRT and HRT groups as a result of training. However, the changes in VO2max, COX-4, redox homeostasis associated markers (reactive oxygen species (ROS)), silent mating-type information regulation 2 homolog (SIRT1), NAD(+)/NADH ratio, proteasome (R2 subunit), and mitochondrial network related proteins such as mitochondrial fission protein 1 (Fis1) and mitochondrial fusion protein (Mfn1) suggest that these markers are not strongly involved in the differences in trainability between LRT and HRT. On the other hand, according to our results, we discovered that differences in basal activity of AMP-activated protein kinase alpha (AMPKα) and differential changes in aerobic exercise-induced responses of citrate synthase, carbonylated protein, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1-α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and Lon protease limit trainability between these selected lines. From this, we conclude that mitochondrial biogenesis-associated factors adapt differently to aerobic exercise training in training sensitive and training resistant rats.

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Figures

Fig. 1
Fig. 1. Maximal oxygen uptake and mitochondrial content
The VO2max (A) and the running distance (B) during VO2max testing were measured every second week during the training period and the intensity was adjusted to 70% of VO2max. The mitochondrial biogenesis was appraised by the COX-4 content (C) and the adaptation to exercise training by Citrate Synthase (CS) activity (D). Low response trainers control LRT (LRTC) (n=6), exercised LRT (LRTE) (n=7), high response trainers control HRT (HRTC) (n=6) and exercised HRT (HRTE) (n=8) groups.* p<0.05 HRTC vs HRTE** p<0.01 HRTC vs HRTE + p<0.05 LRTC vs LRTE++ p<0.01 LRTC vs LRTE. Δ p<0.05 LRTE vs HRTE
Fig. 2
Fig. 2. Oxidative stress markers
The measurements of the ROS levels were done by fluorescent detection of H2DCFDA (A). The ratio of NAD+/NADH was used to evaluate the redox balance (B), while the carbonyl group levels indicate the oxidative modification of proteins (C, D). Low response trainers control LRT (LRTC) (n=6), exercised LRT (LRTE) (n=7), high response trainers control HRT (HRTC) (n=6) and exercised HRT (HRTE) (n=8) groups, * p<0.05 HRTC vs HRTE ** p<0.05 HRTC vs HRTE + p<0.05 LRTC vs LRTE++ p<0.05 LRTC vs LRTE. Δ p<0.05 LRTE vs HRTE
Fig. 3
Fig. 3. Quality control of proteins
The R2 subunit of proteasome (A) mitochondrial Lon Protease (B) and the HSP87 (C) protein content were measured by immunoblot method. Low response trainers control LRT (LRTC) (n=6), exercised LRT (LRTE) (n=7), high response trainers control HRT (HRTC) (n=6) and exercised HRT (HRTE) (n=8) groups, * p<0.05
Fig. 4
Fig. 4. Metabolic markers
The mRNA levels of AMPK were assessed by RT-PCR (A), while activity of AMPK was appraised by the pAMPK/AMPK ratio (B). SIRT1 content was measured by immunoblots (C). Low response trainers control LRT (LRTC) (n=6), exercised LRT (LRTE) (n=7), high response trainers control HRT (HRTC) (n=6) and exercised HRT (HRTE) (n=8) groups, * p<0.05
Fig. 5
Fig. 5. Mitochondrial biogenesis associated transcription factors
Mitochondrial biogenesis-associated transcription factors, such as PGC1-α (A), NRF1 (B), TFAM (C) and mitochondrial fission Fis1 (D) and fusion Mfn1 (E) proteins were measured. Low response trainers control LRT (LRTC) (n=6), exercised LRT (LRTE) (n=7), high response trainers control HRT (HRTC) (n=6) and exercised HRT (HRTE) (n=8) groups, * p<0.05

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