Postexercise whole body heat stress additively enhances endurance training-induced mitochondrial adaptations in mouse skeletal muscle

Abstract

A recent study demonstrated that heat stress induces mitochondrial biogenesis in C2C12 myotubes, thereby implying that heat stress may be an effective treatment to enhance endurance training-induced mitochondrial adaptations in skeletal muscle. However, whether heat stress actually induces mitochondrial adaptations in skeletal muscle in vivo is unclear. In the present study, we report the novel findings that 1) whole body heat stress produced by exposure of ICR mice to a hot environment (40°C, 30 min/day, 5 days/wk, 3 wk) induced mitochondrial adaptations such as increased mitochondrial enzyme activity (citrate synthase and 3-hydroxyacyl CoA dehydrogenase) and respiratory chain protein content (complexes I-V) in skeletal muscle in vivo and 2) postexercise whole body heat stress additively enhanced endurance training-induced mitochondrial adaptations (treadmill running, 25 m/min, 30 min/day, 5 days/wk, 3 wk). Moreover, to determine the candidate mechanisms underlying mitochondrial adaptations, we investigated the acute effects of postexercise whole body heat stress on the phosphorylation status of cellular signaling cascades that subsequently induce mitochondrial gene transcription. We found that whole body heat stress boosted the endurance exercise-induced phosphorylation of p38 MAPK, increased the phosphorylation status of p70S6K, a biomarker of mammalian target of rapamycin complex 1 activity, and unexpectedly dephosphorylated AMP-activated protein kinase and its downstream target acetyl-CoA carboxylase in skeletal muscle. Our present observations suggest that heat stress can act as an effective postexercise treatment. Heat stress treatment appeared to be clinically beneficial for people who have difficulty participating in sufficient exercise training, such as the elderly, injured athletes, and patients.

PGC-1α Mediated Muscle Aerobic Adaptations to Exercise, Heat and Cold Exposure

“…However, a recent study reported decreased AMPK signalling in plantaris and soleus muscles of mice subjected to acute heat exposure (Tamura et al, 2014). Chronic exposure (5 weeks) resulted in increased CS and β-HAD activities as well as protein content of respiratory complexes I-V, however AMPK signalling was not investigated following chronic exposure in this study (Tamura et al, 2014). This disparity in results could be a function of the experimental models used (i.e.…”

“…For instance, in studies using cell culture and animal models, mitochondrial biogenesis has shown to be up-regulated following both heat and cold exposures through PGC-1α dependant mechanisms similar to that observed following exercise (Bruton et al, 2010;Liu & Brooks, 2012;Puigserver et al, 1998;Tamura et al, 2014;Wu et al, 1999). However, when administered following exercise, both heat and cold interventions have demonstrated contradictory results, with some studies showing beneficial, while others detrimental effects on PGC-1α and/or muscle aerobic performance (Ihsan et al, 2014;Slivka et al, 2013;Slivka et al, 2012;Tamura et al, 2014;Yamane et al, 2006). Taken together, these studies highlight the potential of these modalities to both enhance and diminish mitochondrial adaptations to training, as well implicating PGC-1α as a key target in these mechanisms.…”

“…Moreover, heat treatment has also shown to increase AMPK activity and SIRT1 expression, in line with increased PGC-1α and GLUT4 expression, downstream transcription factors (NRFs and Tfam) and respiratory chain complexes I-V in muscle cell cultures (Brooks et al, 1971). However, a recent study reported decreased AMPK signalling in plantaris and soleus muscles of mice subjected to acute heat exposure (Tamura et al, 2014). Chronic exposure (5 weeks) resulted in increased CS and β-HAD activities as well as protein content of respiratory complexes I-V, however AMPK signalling was not investigated following chronic exposure in this study (Tamura et al, 2014).…”

“…This disparity in results could be a function of the experimental models used (i.e. in vivo vs. in vitro) and/or heat exposure conditions (temperature and duration) (Liu & Brooks, 2012;Tamura et al, 2014).…”

“…For instance, short term heat stress (30-45 min at 40-43°C) has shown to result in increased ROS formation and Ca 2+ leakage from sarcoplasmic reticulum in rat diaphragm and skeletal muscle fibres, respectively (van der Poel & Stephenson, 2007;Zuo et al, 2000). However, while both ROS and Ca 2+ are well known primary signals responsible for the induction/activation of PGC-1α and mitochondrial biogenesis, CaMKII, a downstream target of Ca 2+ , and; p38 MAPK, a downstream target of both ROS and Ca 2+ (Gomez-Cabrera et al, 2005;Irrcher et al, 2009;) have shown to not activate following heat treatment in vitro (Yamaguchi et al, 2010) and in vivo (Tamura et al, 2014). As such, it seems that CaMKII and p38 MAPK signalling are not involved in heat-induced PGC-1α mechanisms and ROS and Ca 2+ might act through AMPK-NOS pathways in up-regulating PGC-1α and mediating associated adaptations (Fig.…”