Background: Dysfunctional neutrophils with advanced age are a hallmark of immunosenescence. Reduced migration and bactericidal activity increase the risk of infection. It remains unclear why neutrophil dysfunction occurs with age.
View Article and Find Full Text PDFSynaptosomal-associated protein 23 (SNAP23) is a SNARE protein expressed abundantly in human skeletal muscle. Its established role is to mediate insulin-stimulated docking and fusion of glucose transporter 4 (GLUT4) with the plasma membrane. Recent in vitro research has proposed that SNAP23 may also play a role in the fusion of growing lipid droplets (LDs) and the channeling of LD-derived fatty acids (FAs) into neighboring mitochondria for β-oxidation.
View Article and Find Full Text PDFBackground: Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment.
Purpose: To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT.
Objective: To examine the motivational process through which increases in aerobic capacity and decreases in total body fat are achieved during high-intensity intermittent training (HIT) and moderate-intensity continuous training (MICT) interventions.
Method: Eighty-seven physically inactive adults (65% women, age = 42 ± 12, BMI = 27.67 ± 4.
Insulin- and contraction-stimulated increases in glucose uptake into skeletal muscle occur in part as a result of the translocation of glucose transporter 4 (GLUT4) from intracellular stores to the plasma membrane (PM). This study aimed to use immunofluorescence microscopy in human skeletal muscle to quantify GLUT4 redistribution from intracellular stores to the PM in response to glucose feeding and exercise. Percutaneous muscle biopsy samples were taken from the m.
View Article and Find Full Text PDFIt is becoming increasingly apparent that a high vasodilator response of the skeletal muscle microvasculature to insulin and exercise is of critical importance for adequate muscle perfusion and long-term microvascular and muscle metabolic health. Previous research has shown that a sedentary lifestyle, obesity and ageing lead to impairments in the vasodilator response, while a physically active lifestyle keeps both microvascular density and vasodilator response high. To investigate the molecular mechanisms behind these impairments and the benefits of exercise training interventions, our laboratory has recently developed quantitative immunofluorescence microscopy methods to measure protein content of eNOS and NAD(P)Hoxidase specifically in the endothelial layer of capillaries and arterioles of human skeletal muscle.
View Article and Find Full Text PDFObjectives: The aim of this study was to determine whether short-term treatment with perhexiline improves cardiac energetics, left ventricular function, and symptoms of heart failure by altering cardiac substrate utilization.
Background: Perhexiline improves exercise capacity and left ventricular ejection fraction (LVEF) in patients with heart failure (HF). (31)P cardiac magnetic resonance spectroscopy can be used to quantify the myocardial phosphocreatine/adenosine triphosphate ratio.
J Physiol
April 2016
Key Points: Skeletal muscle capillary density and vasoreactivity are reduced in obesity, due to reduced nitric oxide bioavailability. Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), but its effect on the skeletal muscle microvasculature has not been studied in obese individuals. We observed that SIT and MICT led to equal increases in capillarisation and endothelial eNOS content, while reducing endothelial NOX2 content in microvessels of young obese men.
View Article and Find Full Text PDFThis review concludes that a sedentary lifestyle, obesity and ageing impair the vasodilator response of the muscle microvasculature to insulin, exercise and VEGF-A and reduce microvascular density. Both impairments contribute to the development of insulin resistance, obesity and chronic age-related diseases. A physically active lifestyle keeps both the vasodilator response and microvascular density high.
View Article and Find Full Text PDFIncreases in insulin-mediated glucose uptake following endurance training (ET) and sprint interval training (SIT) have in part been attributed to concomitant increases in glucose transporter 4 (GLUT4) protein content in skeletal muscle. This study used an immunofluorescence microscopy method to investigate changes in subcellular GLUT4 distribution and content following ET and SIT. Percutaneous muscle biopsy samples were taken from the m.
View Article and Find Full Text PDFObjective: The effects of RT on muscle mass, strength, and insulin sensitivity are well established, but the underlying mechanisms are only partially understood. The main aim of this study was to investigate whether RT induces changes in endothelial enzymes of the muscle microvasculature, which would increase NO bioavailability and could contribute to improved insulin sensitivity.
Methods: Eight previously sedentary males (age 20 ± 0.
We sought to determine how the mode of muscle metaboreflex activation influences the central hemodynamic response and cardiac inotropic and lusotropic function in healthy humans. Ten healthy males performed (i) isometric handgrip (IHG) with and without post-exercise ischemia (PEI) to examine the influence of isolated muscle metaboreflex activation and (ii) rhythmic handgrip (RHG) with and without ischemia to examine the influence of enhanced muscle metaboreflex activation. Heart rate (HR) and blood pressure (BP) were continuously monitored.
View Article and Find Full Text PDFFocal adhesion kinase (FAK) and paxillin are functionally linked hormonal- and mechano-sensitive proteins. We aimed to describe paxillin's subcellular distribution using widefield and confocal immunofluorescence microscopy and test the hypothesis that FAK and paxillin colocalise in human skeletal muscle and its associated microvasculature. Percutaneous muscle biopsies were collected from the m.
View Article and Find Full Text PDFBackground: Low heart rate variability (HRV) is associated with increased cardiovascular disease risk. South Asians are at increased risk of cardiovascular disease.
Methods: This cross-sectional, observational study compared long-term HRV between South Asian and White European (EU) children.
Context: It is widely believed that glucocorticoids cause insulin resistance in all tissues. We have previously demonstrated that glucocorticoids cause insulin sensitization in human adipose tissue in vitro and induce insulin resistance in skeletal muscle.
Objective: Our aim was to determine whether glucocorticoids have tissue-specific effects on insulin sensitivity in vivo.
Sprint interval training (SIT) has been proposed as a time efficient alternative to endurance training (ET) for increasing skeletal muscle oxidative capacity and improving certain cardiovascular functions. In this study we sought to make the first comparisons of the structural and endothelial enzymatic changes in skeletal muscle microvessels in response to ET and SIT. Sixteen young sedentary males (age 21 ± SEM 0.
View Article and Find Full Text PDFWithin animal skeletal muscle, focal adhesion kinase (FAK) has been associated with load-dependent molecular and metabolic adaptation including the regulation of insulin sensitivity. This study aimed to generate the first visual images of the localisation of FAK within human skeletal muscle fibres and its associated microvasculature using widefield and confocal immunofluorescence microscopy. Percutaneous muscle biopsies, taken from five lean, active males, were frozen and 5-μm cryosections were incubated with FAK antibodies for visualisation in muscle fibres and the microvasculature.
View Article and Find Full Text PDFObjective: The net production of NO by the muscle microvascular endothelium is a key regulator of muscle microvascular blood flow. Here, we describe the development of a method to quantify the protein content and phosphorylation of endothelial NO synthase (eNOS content and eNOS ser(1177) phosphorylation) and NAD(P)H oxidase expression.
Methods: Human muscle cryosections were stained using antibodies targeting eNOS, p-eNOS ser(1177) and NOX2 in combination with markers of the endothelium and the sarcolemma.
Our first aim was to investigate whether the ingestion of a single high-fat meal impairs glucose tolerance. Our second aim was to investigate whether improvements in glucose tolerance that are seen after resistance exercise remain when exercise is performed after ingestion of a high-fat meal. Eight young males consumed either a high fat (HF) or an isocaloric control (CON) meal in the morning and underwent an oral glucose tolerance test (OGTT) 6 h later.
View Article and Find Full Text PDFIntramuscular triacylglycerol (IMTG) is both a dynamic fat-storage depot that can expand during periods of elevated lipid availability and a fatty acid source that can be utilized during periods of increased energy expenditure in active individuals. Although many studies have investigated the lifestyle determinants of IMTG content, the results are far from consistent, and studies attempting to unravel the mechanisms behind IMTG metabolism are in their infancy. The limited evidence available suggests that the enzymes responsible for skeletal muscle lipolysis and IMTG synthesis play an important role in determining the fate of fatty acids and therefore the concentration of lipid metabolites and insulin sensitivity of skeletal muscle.
View Article and Find Full Text PDFIntramyocellular lipids (IMCL) are stored as discrete lipid droplets which are associated with a number of proteins. The lipid droplet-associated protein adipophilin (the human orthologue of adipose differentiation-related protein) is ubiquitously expressed and is one of the predominant lipid droplet-proteins in skeletal muscle. The aim of this study was to investigate the subcellular distribution of adipophilin in human muscle fibres and to measure the colocalization of adipophilin with IMCL.
View Article and Find Full Text PDFBackground: Short-term high-carbohydrate (HC) diets induce metabolic alterations, including hypertriacylglycerolemia, in both the fasting and postprandial states. The underlying tissue-specific alterations in fatty acid metabolism are not well understood.
Objective: We investigated alterations in exogenous and endogenous fatty acid metabolism by using stable isotope tracers to label meal triacylglycerol and plasma fatty acids.
Purpose: The purpose of this study was to compare substrate source use in older, long-term exercising, endurance-trained males with sedentary controls.
Methods: [U-C]palmitate and [6,6-H2]glucose tracers were applied to assess plasma free fatty acid (FFA) and glucose oxidation rates, and to estimate muscle- and/or lipoprotein-derived triacylglycerol (TG) and muscle glycogen use. Subjects were 10 long-term exercising, endurance-trained males and 10 sedentary controls (age 57 +/- 1 and 60 +/- 2 yr, respectively).
Histochem Cell Biol
January 2008
The objective of the present study was to develop a combination of fluorescent stains that would allow visualisation of the network of mitochondria and lipid droplets (intramyocellular lipids or IMCL) in human skeletal muscle fibres by means of conventional and confocal microscopy. Muscle biopsies were taken from the vastus lateralis of three lean, healthy and physically active male subjects. Frozen muscle sections were stained for mitochondria using antibodies against three mitochondrial proteins; porin, cytochrome c oxidase (COX) and NADH-ubiquinol oxidoreductase and neutral lipids were stained with oil red O.
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