Repeated exposure to heat stress induces mitochondrial adaptation in human skeletal muscle.

The heat stress response is associated with several beneficial adaptations that promote cell health and survival. Specifically, in vitro and animal investigations suggest that repeated exposures to a mild heat stress (~40°C) elicit positive mitochondrial adaptations in skeletal muscle comparable to those observed with exercise. To assess whether such adaptations translate to human skeletal muscle, we produced local, deep tissue heating of the vastus lateralis via pulsed shortwave diathermy in 20 men and women ( n = 10 men; n = 10 women). Diathermy increased muscle temperature by 3.9°C within 30 min of application. Immediately following a single 2-h heating session, we observed increased phosphorylation of AMP-activated protein kinase and ERK1/2 but not of p38 MAPK or JNK. Following repeated heat exposures (2 h daily for 6 consecutive days), we observed a significant cellular heat stress response, as heat shock protein 70 and 90 increased 45% and 38%, respectively. In addition, peroxisome proliferator-activated receptor gamma, coactivator-1 alpha and mitochondrial electron transport protein complexes I and V expression were increased after heating. These increases were accompanied by augmentation of maximal coupled and uncoupled respiratory capacity, measured via high-resolution respirometry. Our data provide the first evidence that mitochondrial adaptation can be elicited in human skeletal muscle in response to repeated exposures to mild heat stress. NEW & NOTEWORTHY Heat stress has been shown to elicit mitochondrial adaptations in cell culture and animal research. We used pulsed shortwave diathermy to produce deep tissue heating and explore whether beneficial mitochondrial adaptations would translate to human skeletal muscle in vivo. We report, for the first time, positive mitochondrial adaptations in human skeletal muscle following recurrent heat stress. The results of this study have clinical implications for many conditions characterized by diminished skeletal muscle mitochondrial function.

CXCL10 increases in human skeletal muscle following damage but is not necessary for muscle regeneration.

CXCL10 is a chemokine for activated and memory T cells with many important immunological functions. We recently found that CXCL10 is upregulated in human muscle following contraction-induced damage. No information is available on the role of CXCL10 in the context of muscle damage or repair. In this study, we confirm that CXCL10 is elevated in human muscle at 2 and 3 days following damage and perform cell culture and animal studies to examine the role of CXCL10 in muscle repair. CXCL10 did not impact proliferation rates of human primary myoblasts but it did promote myogenic differentiation in vitro, suggesting a possible direct impact on muscle regeneration. To test if CXCL10 was dispensable for effective muscle regeneration in vivo, we measured functional and histological markers of muscle repair out to 14 days postmuscle injury caused by a myotoxin in wild-type (WT) mice and CXCL10 knockout (KO) mice. Between genotypes, no significant differences were found in loss or restoration of in situ muscle force, cross-sectional area of newly formed myofibers, or the number of embryonic myosin heavy chain-positive myofibers. In addition, KO animals were not deficient in T-cell accumulation in the damaged muscle following injury. Gene expression of the other two ligands (CXCL9 and 11) that bind to the same receptor as CXCL10 were also elevated in the damaged muscle of KO mice. Thus, other ligands may have compensated for the lack of CXCL10 in the KO mice. We conclude that CXCL10 is not necessary for effective muscle regeneration.