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

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 three 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 (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 (AMPK), 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 limits 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.

Exogenous nicotinamide supplementation and moderate physical exercise can attenuate the aging process in skeletal muscle of rats

“…We and others have shown that exercise increases the activity and content of SIRT1 (Hart et al 2014;Kang et al 2013;Koltai et al 2011;Marton et al 2015;Radak et al 2011;Suwa et al 2008), while aging decreases NAD levels and NAMPT concentration (Koltai et al 2010). Moreover, it has also been reported that exercise training can attenuate the age associated decline in NAD and NAMT levels in skeletal muscle of rats (Koltai et al 2012).…”

Identification of potential mediators of oxidative damage and targets for novel treatments for chronic kidney disease

“…There is a variety of biochemical, cellular, and systemic adaptations that occur in response to exercise that are intimately linked to redox control (Baar, 2014;Marton et al, 2014). ROS increase during and following exercise (Davies et al, 1982; Alessio and Goldfarb, 1988;Radak et al, 2001).…”

“…Mitochondrial biogenesis is a consistent adaptation to exercise, and seems to contribute to the majority of gained benefits to systemic redox control (Baar et al, 2002; Koltai et al, 2012;Marton et al, 2014). Mitochondrial biogenesis is presumed to occur due to increased reliance on aerobic metabolism, and is initiated by increased ROS signalling (Kang et al, 2009).…”

“…This is interesting considering that changes to antioxidant/oxidative stress biomarkers have been demonstrated in various other organs such as brain, kidney, heart and liver, and all appear to have a similar protective response despite reacting differently to changes in oxygen supply during exercise (Radak et al, 1996;Navarro et al, 2004;Radak et al, 2004;Iemitsu et al, 2006;Radak et al, 2008). This suggests that an extracellular source of cytoprotective signalling may account for such a systemic response to exercise.Mitochondrial biogenesis is a consistent adaptation to exercise, and seems to contribute to the majority of gained benefits to systemic redox control (Baar et al, 2002; Koltai et al, 2012;Marton et al, 2014). Mitochondrial biogenesis is presumed to occur due to increased reliance on aerobic metabolism, and is initiated by increased ROS signalling (Kang et al, 2009).…”

“…Nevertheless, convincing, practical and realistic implementation of exercise and lifestyle interventions to large populations of people, let alone chronic disease populations, is an enormous challenge. A greater understanding of the natural ability of the body to invoke a systemic protective 37 response is needed to determine whether these processes can be harnessed for the benefit of the chronic disease population such as CKD.There is a variety of biochemical, cellular, and systemic adaptations that occur in response to exercise that are intimately linked to redox control (Baar, 2014;Marton et al, 2014). ROS increase during and following exercise (Davies et al, 1982; Alessio and Goldfarb, 1988;Radak et al, 2001).…”