No abstract

Heat acclimation (HA) in humans promotes thermoregulatory adaptations that support management of core temperature in hot environments and reduces the likelihood of heat related illness. Another adaptation to HA is thermotolerance through induction of the heat shock protein (HSP) stress system, which provides protection against thermal insult. However, whether or not HA leads to upregulation of the intracellular HSP system, namely intracellular HSP70 (HSP70), is unclear in humans. Therefore, the purposes of this meta-analysis were to determine if HA leads to HSP70 induction among humans and to evaluate how methodological differences among HA studies influence findings regarding HA-induced HSP70 accumulation. Several databases were searched to identify studies that measured HSP70 (protein and mRNA) changes in response to HA among humans. The effect of HA on HSP70 was analyzed. Differences in the effect of HAwere assessed between protein and mRNA. The moderating effect of several independent variables (HA frequency, HA duration, core temperature, exercise intensity) on HSP70 was also evaluated. Data were extracted from 12 studies including 118 participants (mean age 24 years, 98% male). There was a significant effect of HA on HSP70 expression, g = 0.97 (95% CI, 0.08-1.89). The effect of HA was different between subgroups (protein vs. mRNA), g = 1.51 (95% CI, 0.71-2.31), and g = − 0.39 (95% CI, − 1.36), respectively. The frequency of HA (in days) moderated HSP70 protein expression. There was a significant effect of heat acclimation on HSP70 induction in humans. The only factor among identified studies that may moderate this response was the frequency (number of days) of heat exposure.

Chronic hyperglycemia is associated with low response to aerobic exercise training in rodent models and humans, including reduced aerobic exercise capacity and impaired oxidative remodeling in skeletal muscle. Here, we investigated whether glucose lowering with the sodium glucose cotransporter-2 inhibitor (SGLT2i), canagliflozin (Cana; 30 mg/kg/day), could restore exercise training response in a model of hyperglycemia (low dose streptozotocin; STZ). Cana effectively prevented increased blood glucose in STZ-treated mice. After 6 weeks of voluntary wheel running, Cana-treated mice displayed improvements in aerobic exercise capacity, higher capillary density in striated muscle, and a more oxidative fiber-type in skeletal muscle. In contrast, these responses were blunted or absent in STZ mice. Recent work implicates glucose-induced accumulation of skeletal muscle extracellular matrix (ECM) and hyper-activation of JNK/SMAD2 mechanical signaling as potential mechanisms underlying poor exercise response. In line with this, muscle ECM accretion was prevented by Cana in STZ-treated mice. JNK/SMAD2 signaling with acute exercise was 2-fold higher in STZ compared to Control but was normalized by Cana. In human participants, ECM accumulation was associated with increased JNK signaling, low VO2peak and impaired metabolic health (siOGTT). These data demonstrate that hyperglycemia-associated impairments in exercise adaptation can be ameliorated by co-therapy with SGLT2i.

Heat acclimation (HA) increases tolerance to exercise performed in the heat and may improve maximal oxygen uptake (V O 2 max) in temperate environments. However, it is unknown if HA affects the expression of proteins related to mitochondrial biogenesis and oxidative capacity in skeletal muscle. The purpose of this study was to investigate the effect of HA on skeletal muscle markers of mitochondrial biogenesis and oxidative phosphorylation in recreationally trained adults. Thirteen (7 males and 6 females) individuals underwent 10 days of HA. Participants performed two 45 min bouts of exercise (walking at 30-40% maximal velocity at 3% grade) with 10 min rest per session in a hot environment (∼42 • C and 30-50% relative humidity). V O 2 max , ventilatory thresholds (VT), and protein expression of peroxisome proliferatoractivated receptor γ coactivator 1α (PGC-1α), mitochondrial transcription factor A (TFAM), calcium/calmodulin-dependent protein kinase (CaMK), electron transport chain (ETC) complexes I-IV, and heat shock protein 72 (Hsp72) in skeletal muscle were measured pre-and post-HA. Comparing day 1 to day 10, HA was confirmed by lower resting core temperature (T core) (P = 0.026), final T core (P < 0.0001), mean heart rate (HR) (P = 0.002), final HR (P = 0.003), mean ratings of perceived exertion (RPE) (P = 0.026) and final RPE (P = 0.028). Pre-to post-HAV O 2 max (P = 0.045) increased but VT1 (P = 0.263) and VT2 (P = 0.239) were unchanged. Hsp72 (P = 0.007) increased, but skeletal muscle protein expression (PGC-1α, P = 0.119; TFAM, P = 0.763; CaMK,