The relationship between skeletal muscle mitochondrial citrate synthase activity and whole body oxygen uptake adaptations in response to exercise training.

Citrate synthase (CS) activity is a validated biomarker for mitochondrial density in skeletal muscle. CS activity is also used as a biochemical marker of the skeletal muscle oxidative adaptation to a training intervention, and a relationship between changes in whole body aerobic capacity and changes in CS activity is often assumed. However, this relationship and absolute values of CS and maximal oxygen uptake ([Formula: see text]O(2max)) has never been assessed across different studies. A systematic PubMed search on literature published from 1983 to 2013 was performed. The search profile included: citrate, synthase, human, skeletal, muscle, training, not electrical stimulation, not in-vitro, not rats. Studies that reported changes in CS activity and [Formula: see text]O(2max) were included. Different training types and subject populations were analyzed independently to assess correlation between relative changes in [Formula: see text]O(2max) and CS activity. 70 publications with 97 intervention groups were included. There was a positive (r = 0.45) correlation (P < 0.001) between the relative change in [Formula: see text]O(2max) and the relative change in CS activity. All reported absolute values of CS and [Formula: see text]O(2max) did not correlate (r =- 0.07, n = 148, P = 0.4). Training induced changes in whole body oxidative capacity is matched by changes in muscle CS activity in a nearly 1:1 relationship. Absolute values of CS across different studies cannot be compared unless a standardized analytical method is used by all laboratories

Validity and reliability of seismocardiography for the estimation of cardiorespiratory fitness

BACKGROUND: Low cardiorespiratory fitness (ie, peak oxygen consumption [V.O2peak]) is associated with cardiovascular disease and all-cause mortality and is recognized as an important clinical tool in the assessment of patients. Cardiopulmonary exercise test (CPET) is the gold standard procedure for determination of V.O2peak but has methodological challenges as it is time-consuming and requires specialized equipment and trained professionals. Seismofit is a chest-mounted medical device for estimating V.O2peak at rest using seismocardiography.OBJECTIVE: The purpose of this study was to investigate the validity and reliability of Seismofit V.O2peak estimation in a healthy population.METHODS: On 3 separate days, 20 participants (10 women) underwent estimations of V.O2peak with Seismofit (×2) and Polar Fitness Test (PFT) in randomized order and performed a graded CPET on a cycle ergometer with continuous pulmonary gas exchange measurements.RESULTS: Seismofit V.O2peak showed a significant bias of -3.1 ± 2.4 mL·min-1·kg-1 (mean ± 95% confidence interval) and 95% limits of agreement (LoA) of ±10.8 mL·min-1·kg-1 compared to CPET. The mean absolute percentage error (MAPE) was 12.0%. Seismofit V.O2peak had a coefficient of variation of 4.5% ± 1.3% and an intraclass correlation coefficient of 0.95 between test days and a bias of 0.0 ± 0.4 mL·min-1·kg-1 with 95% LoA of ±1.6 mL·min-1·kg-1 in test-retest. In addition, Seismofit showed a 2.4 mL·min-1·kg-1 smaller difference in 95% LoA than PFT compared to CPET.CONCLUSION: The Seismofit is highly reliable in its estimation of V.O2peak. However, based on the measurement error and MAPE &gt;10%, the Seismofit V.O2peak estimation model needs further improvement to be considered for use in clinical settings.</p

An optimized histochemical method to assess skeletal muscle glycogen and lipid stores reveals two metabolically distinct populations of type I muscle fibers

Skeletal muscle energy metabolism has been a research focus of physiologists for more than a century. Yet, how the use of intramuscular carbohydrate and lipid energy stores are coordinated during different types of exercise remains a subject of debate. Controversy arises from contradicting data from numerous studies, which used different methodological approaches. Here we review the "pros and cons" of previously used histochemical methods and describe an optimized method to ensure the preservation and specificity of detection of both intramyocellular carbohydrate and lipid stores. For optimal preservation of muscle energy stores, air drying cryosections or cycles of freezing-thawing need to be avoided. Furthermore, optimization of the imaging settings in order to specifically image intracellular lipid droplets stained with oil red O or Bodipy-493/503 is shown. When co-staining lipid droplets with associated proteins, Bodipy-493/503 should be the dye of choice, since oil red O creates precipitates on the lipid droplets blocking the light. In order to increase the specificity of glycogen stain, an antibody against glycogen is used. The resulting method reveals the existence of two metabolically distinct myosin heavy chain I expressing fibers: I-1 fibers have a smaller crossectional area, a higher density of lipid droplets, and a tendency to lower glycogen content compared to I-2 fibers. Type I-2 fibers have similar lipid content than IIA. Exhaustive exercise lead to glycogen depletion in type IIA and IIX fibers, a reduction in lipid droplets density in both type I-1 and I-2 fibers, and a decrease in the size of lipid droplets exclusively in type I-1 fibers

Training Does Not Alter Muscle Ceramide and Diacylglycerol in Offsprings of Type 2 Diabetic Patients Despite Improved Insulin Sensitivity

Ceramide and diacylglycerol (DAG) may be involved in the early phase of insulin resistance but data are inconsistent in man. We evaluated if an increase in insulin sensitivity after endurance training was accompanied by changes in these lipids in skeletal muscle. Nineteen first-degree type 2 diabetes Offsprings (Offsprings) (age: 33.1±1.4 yrs; BMI: 26.4±0.4 kg/m2) and sixteen matched Controls (age: 31.3±1.5 yrs; BMI: 25.3±0.7 kg/m2) performed 10 weeks of endurance training three times a week at 70% of VO2max on a bicycle ergometer. Before and after the intervention a hyperinsulinemic-euglycemic clamp and VO2max test were performed and muscle biopsies obtained. Insulin sensitivity was significantly lower in Offsprings compared to control subjects (p<0.01) but improved in both groups after 10 weeks of endurance training (Off: 17±6%; Con: 12±9%, p<0.01). The content of muscle ceramide, DAG, and their subspecies were similar between groups and did not change in response to the endurance training except for an overall reduction in C22:0-Cer (p<0.05). Finally, the intervention induced an increase in AKT protein expression (Off: 27±11%; Con: 20±24%, p<0.05). This study showed no relation between insulin sensitivity and ceramide or DAG content suggesting that ceramide and DAG are not major players in the early phase of insulin resistance in human muscle

Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration

This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex II (CII)-driven State 3 mitochondrial respiration were measured separately (State 3:CI and State 3:CII) and in combination (State 3:CI+CII). State 2 respiration was also measured. Exercise tolerance was assessed by knee extensor exercise (KE) time to fatigue. Per milligram of muscle, State 3:CI+CII and State 3:CI were reduced in COPD (P \u3c 0.05), while State 3:CII and State 2 were not different between groups. To determine if this altered pattern of respiration represented qualitative changes in mitochondrial function, respiration states were examined as percentages of peak respiration (State 3:CI+CII), which revealed altered contributions from State 3:CI (Con 83.7 ± 3.4, COPD 72.1 ± 2.4%Peak, P \u3c 0.05) and State 3:CII (Con 64.9 ± 3.2, COPD 79.5 ± 3.0%Peak, P \u3c 0.05) respiration, but not State 2 respiration in COPD. Importantly, a diminished contribution of CI-driven respiration relative to the metabolically less-efficient CII-driven respiration (CI/CII) was also observed in COPD (Con 1.28 ± 0.09, COPD 0.81 ± 0.05, P \u3c 0.05), which was related to exercise tolerance of the patients (r = 0.64, P \u3c 0.05). Overall, this study indicates that COPD is associated with qualitative alterations in skeletal muscle mitochondria that affect the contribution of CI and CII-driven respiration, which potentially contributes to the exercise intolerance associated with this disease

Erythropoietin Treatment Enhances Muscle Mitochondrial Capacity in Humans

Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s−1·mg−1) and ETS (107 ± 4 to 143 ± 14 pmol·s−1·mg−1, p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle