High-fat diet increases electron transfer flavoprotein synthesis and lipid respiration in skeletal muscle during exercise training in female mice.

High-fat diet (HFD) and exercise remodel skeletal muscle mitochondria. The electron transfer flavoproteins (ETF) transfer reducing equivalents from ß-oxidation into the electron transfer system. Exercise may stimulate the synthesis of ETF proteins to increase lipid respiration. We determined mitochondrial remodeling for lipid respiration through ETF in the context of higher mitochondrial abundance/capacity seen in female mice. We hypothesized HFD would be a greater stimulus than exercise to remodel ETF and lipid pathways through increased protein synthesis alongside increased lipid respiration. Female C57BL/6J mice (n = 15 per group) consumed HFD or low-fat diet (LFD) for 4 weeks then remained sedentary (SED) or completed 8 weeks of treadmill training (EX). We determined mitochondrial lipid respiration, RNA abundance, individual protein synthesis, and abundance for ETFα, ETFß, and ETF dehydrogenase (ETFDH). HFD increased absolute and relative lipid respiration (p = 0.018 and p = 0.034) and RNA abundance for ETFα (p = 0.026), ETFß (p = 0.003), and ETFDH (p = 0.0003). HFD increased synthesis for ETFα and ETFDH (p = 0.0007 and p = 0.002). EX increased synthesis of ETFß and ETFDH (p = 0.008 and p = 0.006). Higher synthesis rates of ETF were not always reflected in greater protein abundance. Greater synthesis of ETF during HFD indicates mitochondrial remodeling which may contribute higher mitochondrial lipid respiration through enhanced ETF function.

Muscle oxygen saturation rates coincide with lactate-based exercise thresholds.

INTRODUCTION: Monitoring muscle metabolic activity via blood lactate is a useful tool for understanding the physiological response to a given exercise intensity. Recent indications suggest that skeletal muscle oxygen saturation (SmO2), an index of the balance between local O2 supply and demand, may describe and predict endurance performance outcomes. PURPOSE: We tested the hypothesis that SmO2 rate is tightly related to blood lactate concentration across exercise intensities, and that deflections in SmO2 rate would coincide with established blood lactate thresholds (i.e., lactate thresholds 1 and 2). METHODS: Ten elite male soccer players completed an incremental running protocol to exhaustion using 3-min work to 30 s rest intervals. Blood lactate samples were collected during rest and SmO2 was collected continuously via near-infrared spectroscopy from the right and left vastus lateralis, left biceps femoris and the left gastrocnemius. RESULTS: Muscle O2 saturation rate (%/min) was quantified after the initial 60 s of each 3-min segment. The SmO2 rate was significantly correlated with blood lactate concentrations for all muscle sites; RVL, r = - 0.974; LVL, r = - 0.969; LG, r = - 0.942; LHAM, r = - 0.907. Breakpoints in SmO2 rate were not significantly different from LT1 or LT2 at any muscle sites (P > 0.05). Bland-Altman analysis showed speed threshold estimates via SmO2 rate and lactate are similar at LT2, but slightly greater for SmO2 rate at LT1. CONCLUSIONS: Muscle O2 saturation rate appears to provide actionable information about maximal metabolic steady state and is consistent with bioenergetic reliance on oxygen and its involvement in the attainment of metabolic steady state.

Two weeks of high-intensity interval training increases skeletal muscle mitochondrial respiration via complex-specific remodeling in sedentary humans.

Aerobic training remodels the quantity and quality (function per unit) of skeletal muscle mitochondria to promote substrate oxidation, however, there remain key gaps in understanding the underlying mechanisms during initial training adaptations. We used short-term high-intensity interval training (HIIT) to determine changes to mitochondrial respiration and regulatory pathways that occur early in remodeling. Fifteen normal-weight sedentary adults started seven sessions of HIIT over 14 days and 14 participants completed the intervention. We collected vastus lateralis biopsies before and 48 h after HIIT to determine mitochondrial respiration, RNA sequencing, and Western blotting for proteins of mitochondrial respiration and degradation via autophagy. HIIT increased respiration per mitochondrial protein for lipid (+23% P = 0.020), complex I (+18%, P = 0.0015), complex I + II (+14%, P < 0.0001), and complex II (+24% P < 0.0001). Transcripts that increased with HIIT identified several gene sets of mitochondrial respiration, particularly for complex I, whereas transcripts that decreased identified pathways of DNA and chromatin remodeling. HIIT lowered protein abundance of autophagy markers for p62 (-19%, P = 0.012) and LC3 II/I (-20%, P = 0.004) in whole tissue lysates but not isolated mitochondria. Meal tolerance testing revealed HIIT increased the change in whole body respiratory exchange ratio and lowered cumulative plasma insulin concentrations. Gene transcripts and respiratory function indicate remodeling of mitochondria within 2 wk of HIIT. Overall changes are consistent with increased protein quality driving rapid improvements in substrate oxidation.NEW & NOTEWORTHY Aerobic training stimulates mitochondrial metabolism in skeletal muscle that is linked to improvements to whole body fuel metabolism. The mechanisms driving changes to the quantity and quality (function per unit) of mitochondria are less known. We used seven sessions of high-intensity interval training (HIIT) to determine functional changes and mechanisms of mitochondrial remodeling in skeletal muscle. HIIT increased mitochondrial respiration per mass for fatty acids, complex I, and complex II substrates. HIIT-induced remodeling pathways including gene transcripts for mitochondrial respiration (via RNA sequencing of muscle tissue) and proteins related to complex I respiration. We conclude that an early feature of aerobic training is increased mitochondrial protein quality via improved respiration and induction of mitochondrial transcriptional patterns.

High-intensity interval exercise reduces tolerance to a simulated haemorrhagic challenge in heat-stressed individuals.

NEW FINDINGS: What is the central question of this study? In heat-stressed individuals, does high-intensity interval exercise reduce tolerance to a simulated haemorrhagic challenge (lower body negative pressure, LBNP) relative to steady state exercise? What is the main finding and its importance? LBNP tolerance was lower in heat-stressed individuals following high-intensity interval exercise relative to steady state exercise. This was likely owing to the greater cardiovascular strain required to maintain arterial blood pressure prior to and early during LBNP following high-intensity interval exercise. These findings are of importance for individuals working in occupations in which combined heat stress and intense intermittent exercise are common and where the risk of haemorrhagic injury is increased. ABSTRACT: This study investigated whether tolerance to a simulated haemorrhagic challenge (lower body negative pressure, LBNP) was lower in heat-stressed individuals following high-intensity interval exercise relative to steady state exercise. Nine healthy participants completed two trials (Steady State and Interval). Participants cycled continuously at ∼38% (Steady State) or alternating between 10 and ∼88% (Interval) of the maximal power output whilst wearing a hot water perfused suit until core temperatures increased ∼1.4°C. Participants then underwent LBNP to pre-syncope. LBNP tolerance was quantified as cumulative stress index (CSI; mmHg min). Mean skin and core temperatures were elevated in both trials following exercise prior to LBNP (to 38.1 ± 0.6°C and 38.3 ± 0.2°C, respectively, both P < 0.001 relative to baseline) but not different between trials (both P > 0.05). In the Interval trial, heart rate was greater (122 ± 12 beats min-1 ) prior to LBNP, relative to the Steady State trial (107 ± 8 beats min-1 , P < 0.001) while mean arterial pressure was similarly reduced in both trials prior to LBNP (from baseline 89 ± 5 to 77 ± 7 mmHg; P = 0.001) and at pre-syncope (to 62 ± 9 mmHg, P < 0.001). CSI was lower in the Interval trial (280 ± 194 vs. 550 ± 234 mmHg min; P = 0.0085). In heat-stressed individuals, tolerance to a simulated haemorrhagic challenge is reduced following high-intensity interval exercise relative to steady state exercise.

Improving biologic predictors of cycling endurance performance with near-infrared spectroscopy derived measures of skeletal muscle respiration: E pluribus unum.

The study aim was to compare the predictive validity of the often referenced traditional model of human endurance performance (i.e. oxygen consumption, VO2 , or power at maximal effort, fatigue threshold values, and indices of exercise efficiency) versus measures of skeletal muscle oxidative potential in relation to endurance cycling performance. We hypothesized that skeletal muscle oxidative potential would more completely explain endurance performance than the traditional model, which has never been collectively verified with cycling. Accordingly, we obtained nine measures of VO2 or power at maximal efforts, 20 measures reflective of various fatigue threshold values, 14 indices of cycling efficiency, and near-infrared spectroscopy-derived measures reflecting in vivo skeletal muscle oxidative potential. Forward regression modeling identified variable combinations that best explained 25-km time trial time-to-completion (TTC) across a group of trained male participants (n = 24). The time constant for skeletal muscle oxygen consumption recovery, a validated measure of maximal skeletal muscle respiration, explained 92.7% of TTC variance by itself (Adj R2  = .927, F = 294.2, SEE = 71.2, p < .001). Alternatively, the best complete traditional model of performance, including VO2max (L·min-1 ), %VO2max determined by the ventilatory equivalents method, and cycling economy at 50 W, only explained 76.2% of TTC variance (Adj R2  = .762, F = 25.6, SEE = 128.7, p < .001). These results confirm our hypothesis by demonstrating that maximal rates of skeletal muscle respiration more completely explain cycling endurance performance than even the best combination of traditional variables long postulated to predict human endurance performance.

Small reductions in skin temperature after onset of a simulated hemorrhagic challenge improve tolerance in exercise heat-stressed individuals.

We investigated whether small reductions in skin temperature 60 s after the onset of a simulated hemorrhagic challenge would improve tolerance to lower body negative pressure (LBNP) after exercise heat stress. Eleven healthy subjects completed two trials (High and Reduced). Subjects cycled at ~55% maximal oxygen uptake wearing a warm water-perfused suit until core temperatures increased by ~1.2°C before lying supine and undergoing LBNP to presyncope. LBNP tolerance was quantified as cumulative stress index (CSI; product of each LBNP level multiplied by time; mmHg·min). Skin temperature was similarly elevated from baseline before LBNP and remained elevated 60 s after the onset of LBNP in both High (37.72 ± 0.52°C) and Reduced (37.95 ± 0.54°C) trials (both P < 0.0001). At 60%CSI skin temperature remained elevated in the High trial (37.51 ± 0.56°C) but was reduced to 34.97 ± 0.72°C by the water-perfused suit in the Reduced trial ( P < 0.0001 between trials). Cutaneous vascular conductance was not different between trials [High: 1.57 ± 0.43 vs. Reduced: 1.39 ± 0.38 arbitrary units (AU)/mmHg; P = 0.367] before LBNP but decreased to 0.67 ± 0.19 AU/mmHg at 60%CSI in the Reduced trial while remaining unchanged in the High trial ( P = 0.002 between trials). CSI was higher in the Reduced (695 ± 386 mmHg·min) relative to the High (441 ± 290 mmHg·min; P = 0.023) trial. Mean arterial pressure was not different between trials at presyncope (High: 62 ± 10 vs. Reduced: 62 ± 9 mmHg; P = 0.958). Small reductions in skin temperature after the onset of a simulated hemorrhagic challenge improve LBNP tolerance after exercise heat stress. This may have important implications regarding treatment of an exercise heat-stressed individual (e.g., soldier) who has experienced a hemorrhagic injury.