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Toll-like receptor 4 (TLR4) is an inflammatory receptor expressed ubiquitously in immune cells as well as skeletal muscle and other metabolic tissues. Skeletal muscle develops favorable inflammation-mediated metabolic adaptations from exercise training. Multiple inflammatory myokines, downstream from TLR4, are proposed links to the metabolic benefits of exercise. Additionally, activation of TLR4 alters skeletal muscle substrate preference. Selleckchem HC-258 The role of skeletal muscle TLR4 (mTLR4) in exercise metabolism has not previously been investigated. Herein, we aimed to specifically test the significance of mTLR4 to exercise-induced metabolic adaptations.

We developed a novel muscle-specific TLR4 knockout (mTLR4) mouse model on C57BL/6J background. Male mTLR4 mice and wild type (WT) littermates were compared under sedentary (SED) and voluntary wheel running (WR) conditions for 4 weeks.

mTLR4 deletion revealed marked reductions in downstream interleukin-1 receptor-associated kinase-4 (IRAK4) phosphorylation. In addition, the disruption of mTLR4 signaling prominently blunted the metabolic adaptations in WR-mTLR4 mice as oppose to substantial improvements exhibited by the WT counterparts. Voluntary WR in WT mice, relative to SED, resulted in significant increases in skeletal muscle fatty acid oxidation (FAO), glucose oxidation (GO), and associated mitochondrial enzyme activities, all of which were not significantly changed in mTLR4 mice.

This study introduces a novel mTLR4 mouse model and identifies mTLR4 as an immunomodulatory effector of exercise-induced metabolic adaptations in skeletal muscle.

This study introduces a novel mTLR4 mouse model and identifies mTLR4 as an immunomodulatory effector of exercise-induced metabolic adaptations in skeletal muscle.

Skeletal muscle from lean and obese subjects elicit differential adaptations in response to exercise/muscle contractions. In order to determine whether obesity alters the adaptations in mitochondrial dynamics in response to exercise/muscle contractions and whether any of these distinct adaptations are linked to alterations in insulin sensitivity, we compared the effects of electrical pulse stimulation (EPS) on mitochondrial network structure and regulatory proteins in mitochondrial dynamics in myotubes from lean humans and humans with severe obesity and evaluated the correlations between these regulatory proteins and insulin signaling.

Myotubes from human skeletal muscle cells obtained from lean humans (BMI 23.8 ± 1.67 kg/m) and humans with severer obesity (45.5 ± 2.26 kg/m) (n=8/group) were electrically stimulated for 24 hours. Four-hours after EPS, mitochondrial network structure, protein markers of insulin signaling and mitochondrial dynamics were assessed.

EPS enhanced insulin-stimulated Akt phosphoes more fused mitochondrial networks, which are associated with differential adaptations in mitochondrial dynamic processes in myotubes from lean humans and human with severe obesity. It also suggests that improved insulin signaling following muscle contractions may be linked to the reduction in Drp1 activity.

Sprint interval training (SIT) has gained popularity as a time-effective alternative to moderate-intensity endurance training (END). However, whether SIT is equally effective for decreasing cardiometabolic risk factors remains debatable, as many beneficial effects of exercise are thought to be transient and, unlike END, SIT is not recommended daily. Therefore, in line with current exercise recommendations, we examined the ability of SIT and END to improve cardiometabolic health in overweight/obese males.

Twenty-three participants were randomized to perform 6 weeks of constant workload SIT (3d·wk, 4-6x30 s ~170%Wpeak, 2 min recovery, n=12) or END (5d·wk, 30-40 min, ~60%Wpeak, n=11) on cycle ergometers. Aerobic capacity (VO2peak), body composition, blood pressure (BP), arterial stiffness, endothelial function, glucose and lipid tolerance, and free-living glycemic regulation were assessed pre- and post-training.

Both END and SIT increased VO2peak (END ~15%, SIT ~5%) and glucose tolerance (~20%). However, ocy END improved BP and lipid tolerance, free-living glycemic regulation was better on days which participants exercised, and favorable individual responses were consistent following END, high-frequency END may favorably improve cardiometabolic health.

Exercise-induced laryngeal obstruction (EILO) is a differential diagnosis for asthma and prevalent in athletes referred for exercise-induced dyspnoea. The aim of this study was to estimate the prevalence of EILO in elite cross-country skiers, known for a high prevalence of asthma.

Elite cross-country skiers were invited for screening of EILO. Screening consisted of clinical assessment, questionnaires, skin prick test, spirometry, eucapnic voluntary hyperventilation test, and continuous laryngoscopy during exercise test. Current asthma was defined as physician-diagnosed asthma and use of asthma medication during the last 12 months. EILO was defined as ≥2 points at the supraglottic or glottic level during exercise at maximal effort, using a visual grade score system.

A total of 89 (51% female) cross-country skiers completed the study. EILO was identified in 27% of the skiers, 83% of whom were female. All skiers with EILO had supraglottic EILO, there was no glottic EILO. Current asthma was present in 34 (38%) of the skiers, 10 (29%) of whom had concomitant EILO. In the skiers with EILO, a higher proportion reported wheeze or shortness of breath following exercise, compared to skiers without EILO. In skiers with EILO and current asthma, compared to skiers with asthma only, a higher proportion reported wheeze or shortness of breath following exercise. Asthma medication usage did not differ between these groups.

EILO is common in elite cross-country skiers, especially females. Asthma and EILO may co-exist, and the prevalence of respiratory symptoms is higher in skiers with both. Testing for EILO should be considered in cross-country skiers with respiratory symptoms.

EILO is common in elite cross-country skiers, especially females. Asthma and EILO may co-exist, and the prevalence of respiratory symptoms is higher in skiers with both. Testing for EILO should be considered in cross-country skiers with respiratory symptoms.