Long-term heat acclimation training in mice: Similar metabolic and running performance adaptations despite a lower absolute intensity than training at temperate conditions.

This study investigated the impact of long-term heat acclimation (HA) training on mouse thermoregulation, metabolism, and running performance in temperate (T) and hot (H) environments. Male Swiss mice were divided into 1) Sedentary (SED) mice kept in T (22 °C; SED/T), 2) Endurance Trained mice (ET, 1 h/day, 5 days/week, 8 weeks, 60 % of maximum speed) in T (ET/T), 3) SED kept in H (32 °C; SED/H), and 4) ET in H (ET/H). All groups performed incremental load tests (ILT) in both environments before (pre-ET) and after four and eight weeks of ET. In the pre-ET period, H impaired (∼30 %) performance variables (maximum speed and external work) and increased (1.3 °C) maximum abdominal body temperature compared with T. In T, after four weeks, although ET/H exercised at a lower (∼30 %) absolute intensity than ET/T, performance variables and aerobic power (peak oxygen uptake, VO2peak) were similarly increased in both ET groups compared with SED/T. After eight weeks, the external work was higher in both ET groups compared with SED/T. Only ET/T significantly increased VO2peak (∼11 %) relative to its pre-ET period. In H, only after eight weeks, both ET groups improved (∼19 %) maximum speed and reduced (∼46 %) post-ILT blood lactate concentrations compared with their respective pre-ET values. Liver glycogen content increased (34 %) in both ET groups and SED/H compared with SED/T. Thus, ET/H was performed at a lower absolute intensity but promoted similar effects to ET/T on metabolism, aerobic power, and running performance. Our findings open perspectives for applying HA training as part of a training program or orthopedic and metabolic rehabilitation programs in injured or even obese animals, reducing mechanical load with equivalent or higher physiological demand.

Sleep impairment and altered pattern of circadian biomarkers during a long-term Antarctic summer camp.

Antarctic expeditions include isolation and exposure to cold and extreme photoperiods (with continuous natural light during summer) that may influence psychophysiological responses modulated by luminosity and sleep. We assessed changes in night sleep patterns by actigraphy, salivary biomarkers, and perceptual variables in seven participants in the following time points along a 50-day camping expedition in Antarctica (Nelson Island): Pre-Field (i.e., on the ship before camp), Field-1, Field-2, Field-3, Field-4 (from 1st to 10th, 11th to 20th, 21st to 35th and 36th to 50th days in camp, respectively), and Post-Field (on the ship after camp). We also characterized mood states, daytime sleepiness, and sleep quality by questionnaires. Staying in an Antarctic camp reduced sleep efficiency (5.2%) and increased the number of awakenings and wakefulness after sleep onset (51.8% and 67.1%, respectively). Furthermore, transient increases in time in bed (16.5%) and sleep onset latency (4.8 ± 4.0 min, from Pre- to Field-3) was observed. These changes were accompanied by an altered pattern of the emerging circadian marker ß-Arrestin-1 and a trend to reduce nocturnal melatonin [57.1%; P = 0.066, with large effect size (ES) from Pre-Field to Field-2 (ES = 1.2) and Field-3 (ES = 1.2)]. All changes returned to Pre-Field values during the Post-Field. The volunteers reported sleep-related physical complaints (feeling of cold and pain, discomfort to breathe, and cough or loud snoring), excessive daytime sleepiness, and reduced vigor during the camp. Thus, a 50-day camp alters neuroendocrine regulation and induces physical discomfort, which may explain the impaired sleep pattern and the consequent daytime sleepiness and mood changes.

Do executive function performance, gaze behavior, and pupil size change during incremental acute physical exercise?

Several studies have investigated the interaction between acute physical exercise and cognitive performance. However, few studies have investigated this issue during acute high-intensity exercise. In the present study, we evaluated executive functions (EFs) during incremental exercise in three different intensities [below lactate threshold (LT), at LT, and above LT], measuring EFs performance, gaze behavior, and pupil diameter. Twenty subjects were familiarized with the EFs test and participated in a graded maximal exercise test on a cycle ergometer on the first visit. On the second visit, they performed the EFs task at rest and while exercising at three different intensities using mobile eye-tracking glasses. Our results showed that the psychophysiological measures differed between the conditions. Regarding EFs performance, during exercise above LT, the subjects showed worse accuracy when compared with rest (p < .001) and below LT (p < .001). In addition, the response time (RT) at LT and above LT was shorter than in the rest condition (p < .050). Further, RT was faster (p = .002) in the above LT than in the below LT condition. In addition, the gaze behavior measures indicated that exercise, independently of the intensity, improves the number of fixations with shorter fixation durations compared to the rest condition (p < .050). Additionally, we found no significant differences in average and peak pupil diameter between conditions. In conclusion, exercise at LT improves the EFs performance while exercising above LT worsens EFs performance. However, there were no significant differences in average and peak pupil diameter between conditions.

Sympathetic innervation suppresses the autophagic-lysosomal system in brown adipose tissue under basal and cold-stimulated conditions.

The sympathetic nervous system (SNS) activates cAMP signaling and promotes trophic effects on brown adipose tissue (BAT) through poorly understood mechanisms. Because norepinephrine has been found to induce antiproteolytic effects on muscle and heart, we hypothesized that the SNS could inhibit autophagy in interscapular BAT (IBAT). Here, we describe that selective sympathetic denervation of rat IBAT kept at 25°C induced atrophy, and in parallel dephosphorylated forkhead box class O (FoxO), and increased cathepsin activity, autophagic flux, autophagosome formation, and expression of autophagy-related genes. Conversely, cold stimulus (4°C) for up to 72 h induced thermogenesis and IBAT hypertrophy, an anabolic effect that was associated with inhibition of cathepsin activity, autophagic flux, and autophagosome formation. These effects were abrogated by sympathetic denervation, which also upregulated Gabarapl1 mRNA. In addition, the cold-driven sympathetic activation stimulated the mechanistic target of rapamycin (mTOR) pathway, leading to the enhancement of protein synthesis, evaluated in vivo by puromycin incorporation, and to the inhibitory phosphorylation of Unc51-like kinase-1, a key protein in the initiation of autophagy. This coincided with a higher content of exchange protein-1 directly activated by cAMP (Epac1), a cAMP effector, and phosphorylation of Akt at Thr308, all these effects being abolished by denervation. Systemic treatment with norepinephrine for 72 h mimicked most of the cold effects on IBAT. These data suggest that the noradrenergic sympathetic inputs to IBAT restrain basal autophagy via suppression of FoxO and, in the setting of cold, stimulate protein synthesis via the Epac/Akt/mTOR-dependent pathway and suppress the autophagosome formation, probably through posttranscriptional mechanisms.NEW & NOTEWORTHY The underlying mechanisms related to the anabolic role of sympathetic innervation on brown adipose tissue (BAT) are unclear. We show that sympathetic denervation activates autophagic-lysosomal degradation, leading to a loss of mitochondrial proteins and BAT atrophy. Conversely, cold-driven sympathetic activation suppresses autophagy and stimulates protein synthesis, leading to BAT hypertrophy. Given its high-potential capacity for heat production, understanding the mechanisms that contribute to BAT mass is important to optimize chances of survival for endotherms in cold ambients.

Morphological and molecular aspects of immobilization-induced muscle atrophy in rats at different stages of postnatal development: the role of autophagy.

Muscle loss occurs following injury and immobilization in adulthood and childhood, which impairs the rehabilitation process; however, far fewer studies have been conducted analyzing atrophic response in infants. This work investigated first the morphological and molecular mechanisms involved in immobilization-induced atrophy in soleus muscles from rats at different stages of postnatal development [i.e., weanling (WR) and adult (AR) rats] and, second, the role of autophagy in regulating muscle plasticity during immobilization. Hindlimb immobilization for 10 days reduced muscle mass and fiber cross-sectional area, with more pronounced atrophy in WR, and induced slow-to-fast fiber switching. These effects were accompanied by a decrease in markers of protein synthesis and an increase in autophagy. The ubiquitin (Ub)-ligase MuRF1 and the ubiquitinated proteins were upregulated by immobilization in AR while the autolyzed form of µ-calpain was increased in WR. To further explore the role of autophagy in muscle abnormalities, AR were concomitantly immobilized and treated with colchicine, which blocks autophagosome-lysosome fusion. Colchicine-treated immobilized muscles had exacerbated atrophy and presented degenerative features. Despite Igf1/Akt signaling was downregulated in immobilized muscles from both age groups, Foxo1 and 4 phosphorylation was increased in WR. In the same group of animals, Foxo1 acetylation and Foxo1 and 4 content was increased and decreased, respectively. Our data show that muscle disorders induced by 10-day-immobilization occur in both age-dependent and -independent manners, an understanding that may optimize treatment outcomes in infants. We also provide further evidence that the strong inhibition of autophagy may be ineffective for treating muscle atrophy.

Cyclic adenosine monophosphate-phosphodiesterase inhibitors reduce skeletal muscle protein catabolism in septic rats.

We have previously shown that catecholamines exert an inhibitory effect on muscle protein degradation through a pathway involving the cyclic adenosine monophosphate (cAMP) cascade in normal rats. In the present work, we investigated in vivo and in vitro effects of cAMP-phosphodiesterase inhibitors on protein metabolism in skeletal muscle from rats submitted to a model of acute sepsis. The in vivo muscle protein metabolism was evaluated indirectly by measurements of the tyrosine interstitial concentration using microdialysis. Muscle blood flow (MBF) was monitored by ethanol perfusion technique. Sepsis was induced by cecal ligation and puncture and resulted in lactate acidosis, hypotension, and reduction in MBF (-30%; P < 0.05). Three-hour septic rats showed an increase in muscle interstitial tyrosine concentration (approximately 150%), in arterial plasma tyrosine levels (approximately 50%), and in interstitial-arterial tyrosine concentration difference (approximately 200%; P < 0.05). Pentoxifylline (50 mg/kg of body weight, i.v.) infusion during 1 h after cecal ligation and puncture prevented the tumor necrosis factor alpha increase and significantly reduced by 50% (P < 0.05) the interstitial-arterial tyrosine difference concentration. In situ perfusion with isobutylmethylxanthine (IBMX; 10(-3) M) reduced by 40% (P < 0.05) the muscle interstitial tyrosine in both sham-operated and septic rats. Neither pentoxifylline nor IBMX altered MBF. The addition of IBMX (10(-3) M) to the incubation medium increased (P < 0.05) muscle cAMP levels and reduced proteolysis in both groups. The in vitro addition of H89, a protein kinase A inhibitor, completely blocked the antiproteolytic effect of IBMX. The data show that activation of cAMP-dependent pathways and protein kinase A reduces muscle protein catabolism during basal and septic state.