scholarly journals Loss of α-actinin-3 during human evolution provides superior cold resilience and muscle heat generation

2020 ◽  
Author(s):  
VL Wyckelsma ◽  
T Venckunas ◽  
PJ Houweling ◽  
M Schlittler ◽  
VM Lauschke ◽  
...  

ABSTRACTThe fast skeletal muscle protein α-actinin-3 is absent in 1.5 billion people worldwide due to homozygosity for a nonsense polymorphism in the ACTN3 gene (R577X) 1. The prevalence of the 577X allele increased as modern humans moved to colder climates, suggesting a link between α-actinin-3 deficiency and improved cold tolerance 1,2. Here, we show that humans lacking α-actinin-3 (XX) are superior in maintaining core body temperature during cold-water immersion due to changes in skeletal muscle thermogenesis. Muscles of XX individuals displayed a shift towards more slow-twitch isoforms of myosin heavy chain (MyHC) and sarcoplasmic reticulum (SR) proteins, accompanied by altered neuronal muscle activation resulting in increased tone rather than overt shivering 3,4. Experiments on Actn3 knockout mice showed no alterations in brown adipose tissue (BAT) properties that could explain the improved cold tolerance in XX individuals. Thus, this study provides a clear mechanism for the positive selection of the ACTN3 X-allele in cold climates and supports a key thermogenic role of skeletal muscle during cold exposure in humans.

2019 ◽  
Vol 127 (5) ◽  
pp. 1403-1418 ◽  
Author(s):  
Jackson J. Fyfe ◽  
James R. Broatch ◽  
Adam J. Trewin ◽  
Erik D. Hanson ◽  
Christos K. Argus ◽  
...  

We determined the effects of cold water immersion (CWI) on long-term adaptations and post-exercise molecular responses in skeletal muscle before and after resistance training. Sixteen men (22.9 ± 4.6 y; 85.1 ± 17.9 kg; mean ± SD) performed resistance training (3 day/wk) for 7 wk, with each session followed by either CWI [15 min at 10°C, CWI (COLD) group, n = 8] or passive recovery (15 min at 23°C, control group, n = 8). Exercise performance [one-repetition maximum (1-RM) leg press and bench press, countermovement jump, squat jump, and ballistic push-up], body composition (dual X-ray absorptiometry), and post-exercise (i.e., +1 and +48 h) molecular responses were assessed before and after training. Improvements in 1-RM leg press were similar between groups [130 ± 69 kg, pooled effect size (ES): 1.53 ± 90% confidence interval (CI) 0.49], whereas increases in type II muscle fiber cross-sectional area were attenuated with CWI (−1,959 ± 1,675 µM2 ; ES: −1.37 ± 0.99). Post-exercise mechanistic target of rapamycin complex 1 signaling (rps6 phosphorylation) was blunted for COLD at post-training (POST) +1 h (−0.4-fold, ES: −0.69 ± 0.86) and POST +48 h (−0.2-fold, ES: −1.33 ± 0.82), whereas basal protein degradation markers (FOX-O1 protein content) were increased (1.3-fold, ES: 2.17 ± 2.22). Training-induced increases in heat shock protein (HSP) 27 protein content were attenuated for COLD (−0.8-fold, ES: −0.94 ± 0.82), which also reduced total HSP72 protein content (−0.7-fold, ES: −0.79 ± 0.57). CWI blunted resistance training-induced muscle fiber hypertrophy, but not maximal strength, potentially via reduced skeletal muscle protein anabolism and increased catabolism. Post-exercise CWI should therefore be avoided if muscle hypertrophy is desired. NEW & NOTEWORTHY This study adds to existing evidence that post-exercise cold water immersion attenuates muscle fiber growth with resistance training, which is potentially mediated by attenuated post-exercise increases in markers of skeletal muscle anabolism coupled with increased catabolism and suggests that blunted muscle fiber growth with cold water immersion does not necessarily translate to impaired strength development.


2011 ◽  
Vol 90 (5) ◽  
pp. 356-363 ◽  
Author(s):  
Juan Manuel García-Manso ◽  
Darío Rodríguez-Matoso ◽  
David Rodríguez-Ruiz ◽  
Samuel Sarmiento ◽  
Yves de Saa ◽  
...  

2017 ◽  
Author(s):  
Danny Christiansen ◽  
Robyn M. Murphy ◽  
James R. Broatch ◽  
Jens Bangsbo ◽  
Michael J. McKenna ◽  
...  

AbstractWe investigated the effect of a session of sprint-interval exercise on the mRNA content of NKA isoforms (α1-3, β1-3) and FXYD1 in human skeletal muscle. To explore some of the cellular stressors involved in this regulation, we evaluated the association between these mRNA responses and those of the transcription factors Sp1, Sp3 and HIF-1α. Given cold exposure perturbs muscle redox homeostasis, which may be one mechanism important for increases in NKA-isoform mRNA, we also explored the effect of post-exercise cold-water immersion (CWI) on the mRNA responses. Muscle was sampled from nineteen men before (Pre) and after (+0h, +3h) exercise plus passive rest (CON, n=10) or CWI (10°C; COLD, n=9). In COLD, exercise increased NKAα2 and Sp1 mRNA (+0h, p<0.05). These genes remained unchanged in CON (p>0.05). In both conditions, exercise increased NKAα1, NKAβ3 and HIF-1α mRNA (+3h; p <0.05), decreased NKAβ2 mRNA (+3h; p<0.05), whereas NKAα3, NKAβ1, FXYD1 and Sp3 mRNA remained unchanged (p>0.05). These human findings highlight 1) sprint-interval exercise increases the mRNA content of NKA α1 and β3, and decreases that of NKA β2, which may relate, in part, to exercise-induced muscle hypoxia, and 2) post-exercise CWI augments NKAα2 mRNA, which may be associated with promoted Sp1 activation.


2020 ◽  
Vol 11 ◽  
Author(s):  
Jonathan M. Peake ◽  
James F. Markworth ◽  
Kristoffer Toldnes Cumming ◽  
Sigve N. Aas ◽  
Llion A. Roberts ◽  
...  

1988 ◽  
Vol 65 (5) ◽  
pp. 2046-2050 ◽  
Author(s):  
L. Martineau ◽  
I. Jacobs

The purpose of the present study was to clarify the importance of skeletal muscle glycogen as a fuel for shivering thermogenesis in humans during cold-water immersion. Fourteen seminude subjects were immersed to the shoulders in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Biopsies from the vastus lateralis muscle and venous blood samples were obtained before and immediately after the immersion. Metabolic rate increased during the immersion to 3.5 +/- 0.3 (SE) times resting values, whereas Tre decreased by 0.9 degrees C to approximately 35.8 degrees C at the end of the immersion. Intramuscular glycogen concentration in the vastus lateralis decreased from 410 +/- 15 to 332 +/- 18 mmol glucose/kg dry muscle, with each subject showing a decrease (P less than 0.001). Plasma volume decreased (P less than 0.001) markedly during the immersion (-24 +/- 1%). After correcting for this decrease, blood lactate and plasma glycerol levels increased by 60 (P less than 0.05) and 38% (P less than 0.01), respectively, whereas plasma glucose levels were reduced by 20% after the immersion (P less than 0.001). The mean expiratory exchange ratio showed a biphasic pattern, increasing initially during the first 30 min of the immersion from 0.80 +/- 0.06 to 0.85 +/- 0.05 (P less than 0.01) and decreasing thereafter toward basal values. The results demonstrate clearly that intramuscular glycogen reserves are used as a metabolic substrate to fuel intensive thermogenic shivering activity of human skeletal muscle.


2017 ◽  
Vol 26 (3) ◽  
pp. 286-289
Author(s):  
Megan L. Keen ◽  
Kevin C. Miller

Clinical Scenario:Exercise performed in hot and humid environments increases core body temperature (TC). If TC exceeds 40.5°C for prolonged periods of time, exertional heat stroke (EHS) may occur. EHS is a leading cause of sudden death in athletes. Mortality and morbidity increase the longer the patient’s TC remains above 40.5°C; thus, it is imperative to initiate cooling as quickly as possible. Acceptable cooling rates in EHS situations are 0.08–0.15°C/min, while ideal cooling rates are above 0.16°C/min. Cooling vests are popular alternatives for cooling hyperthermic adults. Most vests cover the anterior and posterior torso and have varying numbers of pouches for phase-change materials (eg, gel packs); some vests only use circulating water to cool. While cooling vests offer several advantages (eg, portability), studies demonstrating their effectiveness at rapidly reducing TC in EHS scenarios are limited.Clinical Question:Are TC cooling rates acceptable (ie, >0.08°C/min) when hyperthermic humans are treated with cooling vests postexercise?Summary of Findings:No significant differences in TC cooling rates occurred between cooling vests and no cooling vests. Cooling rates across all studies were ≤0.053°C/min.Clinical Bottom Line:Cooling vests do not provide acceptable cooling rates of hyperthermic humans postexercise and should not be used to treat EHS. Instead, EHS patients should be treated with cold-water immersion within 30 min of collapse to avoid central nervous system dysfunction and organ failure.Strength of Recommendation:Strong evidence (eg, level 2 studies with PEDro scores ≥5) suggests that cooling vests do not reduce TC quickly and thus should not be used in EHS scenarios.


2021 ◽  
Vol 43 (2) ◽  
pp. 230-239
Author(s):  
Tohid Hemmatzade Bedovli ◽  
Maryam Nourshahi ◽  
Rana Fayaz Milani ◽  
Siavash Parvarde

Background: Oxidative stress and inflammation increase after eccentric exercise. Cold-water immersion after exercise is common among athletes to accelerate recovery. Therefore, the purpose of this study was to investigate the effect of cold-water immersion after eccentric exercise on the oxidative and inflammatory responses in skeletal muscle. Methods: One hundred male Wistar rats (weight 285.11 ± 41.65) were randomly divided into control, eccentric exercise, eccentric exercise + normal water, and eccentric exercise + cold water groups. Half, 24, 48, 72, and 168 hours after eccentric exercise, EDL muscle was removed in sterile conditions. The eccentric exercise involves 90 minutes of interval running on the treadmill at a speed of 16 m/min and a -16-degree slope. Muscle reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-α) levels were measured by DCFDA and immunohistochemical staining. Kolmogorov-Smirnov for normality test and repeated measure ANOVA and Tukey’s post-Hoc tests for compare groups were used with a significance level of P≤0.05. Results: After eccentric exercise, ROS and TNF-α levels significantly (P<0.05) increased in the three experimental groups. The peak of ROS increase in the eccentric exercise, eccentric exercise + normal water, and eccentric exercise + cold water groups were recorded significantly (P<0.001) half, 48, and 72 hours after eccentric exercise, respectively. Also, the peak of TNF-α increase was significantly higher in the eccentric exercise and eccentric exercise + normal water groups were at 48 hours and in the eccentric exercise + cold water groups was at 72 hours after eccentric exercise (P<0.001). Conclusion: Immersion in cold water causes an increase and delays the peak of ROS and TNF-α after eccentric exercise, which is probably related to ischemia-reperfusion injury. Therefore, after unaccustomed, eccentric, and damaging exercise, immersion in cold water is not recommended.


2017 ◽  
Vol 12 (3) ◽  
pp. 179-187 ◽  
Author(s):  
Kristen Couper Schellhase ◽  
Jennifer Plant ◽  
Stephanie M. Mazerolle

Context: Death from exertional heat stroke (EHS) is preventable when evidence-based guidelines are followed. The assessment of core body temperature using rectal thermometry and the treatment of cold-water immersion for EHS has been established as the standard of care; however, rectal thermometry is still controversial. Athletic trainers (ATs) may lack knowledge and comfort with this skill, which could impact implementation. Objective: Examine ATs' current practices, attitudes, and perceptions regarding EHS before and after an educational intervention. Design: Prequantitative/postquantitative experimental. Setting: Classroom. Patients or Other Participants: Twenty-five ATs in various athletic training settings. Intervention(s): Educational intervention designed to increase knowledge and address negative attitudes and perceptions regarding EHS evaluation and treatment. Main Outcome Measure(s): Attitude and perception scores. Results: Prior to the educational intervention, most ATs (86.9%, 20/23) reported that they use methods other than rectal thermometry to evaluate EHS. Of those who did not use rectal thermometry, their reasons included: lack of equipment/budget, concerns about liability/lack of consent (especially when dealing with minors), lack of training, and/or concerns about the privacy, embarrassment, compliance of the athlete. Cold-water immersion was chosen as the definitive method of cooling an athlete by only 41.7% (n = 10) of participants. Following the educational intervention, attitudes toward the use of rectal temperature to assess core body temperature (t[24] = 8.663, P &lt; .001) and cold-water immersion treatment for EHS (t[24] = 4.187, P &lt; .001) were significantly improved. However, while attitudes toward the use of other “cold” methods to treat EHS were not significantly changed (t[24] = 1.684, P = .105), perceptions regarding nonexertional influences on EHS were significantly improved (t[24] = 1.684, P = .105). Conclusions: This study demonstrated that a 3-hour educational intervention can improve attitudes and perceptions regarding the assessment and treatment of EHS in the short term. It is important that educational interventions use best-practice continuing education methods and include special attention to the barriers to evidence-based practice.


Platelets ◽  
2020 ◽  
Vol 31 (8) ◽  
pp. 1039-1051 ◽  
Author(s):  
Rodrigo Pereira Martins ◽  
Diane Duarte Hartmann ◽  
Andrezza Bond Vieira Furtado ◽  
Bárbara Santos Luccas Duarte ◽  
Luis Ulisses Signori ◽  
...  

2017 ◽  
Vol 123 (2) ◽  
pp. 451-459 ◽  
Author(s):  
Robert Allan ◽  
Adam P. Sharples ◽  
Graeme L. Close ◽  
Barry Drust ◽  
Sam O. Shepherd ◽  
...  

Mechanisms mediating postexercise cold-induced increases in PGC-1α gene expression in human skeletal muscle are yet to be fully elucidated but may involve local cooling effects on AMPK and p38 MAPK-related signaling and/or increased systemic β-adrenergic stimulation. Therefore, we aimed to examine whether postexercise cold water immersion enhancement of PGC-1α mRNA is mediated through local or systemic mechanisms. Ten subjects completed acute cycling (8 × 5 min at ~80% peak power output) followed by seated-rest (CON) or single-leg cold water immersion (CWI; 10 min, 8°C). Muscle biopsies were obtained preexercise, postexercise, and 3 h postexercise from a single limb in the CON condition but from both limbs in CWI [thereby providing tissue from a CWI and nonimmersed limb (NOT)]. Muscle temperature decreased up to 2 h postexercise following CWI (−5°C) in the immersed limb, with lesser changes observed in CON and NOT (−3°C, P < 0.05). No differences between limbs were observed in p38 MAPK phosphorylation at any time point ( P < 0.05), whereas a significant interaction effect was present for AMPK phosphorylation ( P = 0.031). Exercise (CON) increased gene expression of PGC-1α 3 h postexercise (~5-fold, P < 0.001). CWI augmented PGC-1α expression above CON in both the immersed (CWI; ~9-fold, P = 0.003) and NOT limbs (~12-fold, P = 0.001). Plasma normetanephrine concentration was higher in CWI vs. CON immediately postimmersion (860 vs. 665 pmol/l, P = 0.034). We report for the first time that local cooling of the immersed limb evokes transcriptional control of PGC-1α in the nonimmersed limb, suggesting increased systemic β-adrenergic activation of AMPK may mediate, in part, postexercise cold induction of PGC-1α mRNA. NEW & NOTEWORTHY We report for the first time that postexercise cold water immersion of one limb also enhances PGC-1α expression in a contralateral, nonimmersed limb. We suggest that increased systemic β-adrenergic stimulation, and not localized cooling per se, exerts regulatory effects on local signaling cascades, thereby modulating PGC-1α expression. Therefore, these data have important implications for research designs that adopt contralateral, nonimmersed limbs as a control condition while also increasing our understanding of the potential mechanisms underpinning cold-mediated PGC-1α responses.


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