Matthew Cocks

Sprint interval and traditional endurance training increase net intramuscular triglyceride breakdown and expression of perilipin 2 and 5

Increases in aerobic capacity and intramuscular triglyceride (IMTG) utilization are well‐described adaptations to endurance training (ET) and contribute to improvements in insulin sensitivity. Sprint interval training (SIT) also improves aerobic capacity and insulin sensitivity with a lower time commitment than ET. This study aimed to determine whether SIT also induces improvements in insulin sensitivity and net IMTG breakdown, and to investigate the underlying mechanisms. Six weeks of ET and SIT increased net IMTG breakdown during moderate‐intensity cycling, and improved insulin sensitivity. A greater concentration of lipid droplet‐associated proteins, perilipin 2 and perilipin 5, was observed following both training modes and contributes to the increases in net IMTG breakdown following training. The results suggest a novel mechanism for the training‐induced improvements in IMTG breakdown and insulin sensitivity, and clearly demonstrate that SIT is an alternative, time‐efficient training strategy that induces similar beneficial metabolic adaptations.

Sprint interval and endurance training are equally effective in increasing muscle microvascular density and eNOS content in sedentary males

Optimal vascular function is critical for health, and endurance training (ET) has previously been shown to be an effective method of improving this. Sprint interval training (SIT) has been proposed as a time efficient alternative to ET but its effect on skeletal muscle microvasculature has not been studied and no direct comparison with ET has been made. ET and SIT in this study were equally effective at decreasing arterial stiffness and increasing skeletal muscle capillarisation and eNOS content. The main results suggest that both training modes improve skeletal muscle microvascular and macrovascular function, with SIT being a time efficient alternative.

Preferential utilization of perilipin 2‐associated intramuscular triglycerides during 1 h of moderate‐intensity endurance‐type exercise

The lipid droplet (LD)‐associated protein perilipin 2 (PLIN2) appears to colocalize with LDs in human skeletal muscle fibres, although the function of PLIN2 in the regulation of intramuscular triglyceride (IMTG) metabolism is currently unknown. Here we investigated the hypothesis that the presence of PLIN2 in skeletal muscle LDs is related to IMTG utilisation during exercise. We therefore measured exercise‐induced changes in IMTG and PLIN2 distribution and changes in their colocalization. Muscle biopsies from the vastus lateralis were obtained from seven lean, untrained men (22 ± 2 years old, body mass index 24.2 ± 0.9 kg m−2 and peak oxygen uptake 3.35 ± 0.13 l min−1) before and after 1 h of moderate‐intensity cycling at ∼65% peak oxygen uptake. Cryosections were stained for perilipin 2, IMTG and myosin heavy chain type I and viewed using wide‐field and confocal fluorescence microscopy. Exercise induced a 50 ± 7% decrease in IMTG content in type I fibres only (P < 0.05), but no change in PLIN2 content. Colocalization analysis showed that the fraction of PLIN2 associated with IMTG was 0.67 ± 0.03 before exercise, which was reduced to 0.51 ± 0.01 postexercise (P < 0.05). Further analysis revealed that the number of PLIN2‐associated LDs was reduced by 31 ± 10% after exercise (P < 0.05), whereas the number of PLIN2‐null LDs was unchanged. No such changes were seen in type II fibres. In conclusion, this study shows that PLIN2 content in skeletal muscle is unchanged in response to a single bout of endurance exercise. Furthermore, the PLIN2 and IMTG association is reduced postexercise, apparently due to preferential utilization of PLIN2‐associated LDs. These results confirm the hypothesis that the PLIN2 association with IMTG is related to the utilization of IMTG as a fuel during exercise.

Sprint interval and moderate‐intensity continuous training have equal benefits on aerobic capacity, insulin sensitivity, muscle capillarisation and endothelial eNOS/NAD(P)Hoxidase protein ratio in obese men

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. We conclude that SIT is equally effective at improving skeletal muscle capillarisation and endothelial enzyme balance, while being a time efficient alternative to traditional MICT.

Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: effect of obesity and ageing

This 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. Intravital microscopy has shown that microvascular units (MVUs) are the smallest functional elements to adjust blood flow in response to physiological signals and metabolic demands on muscle fibres. The luminal diameter of a common terminal arteriole (TA) controls blood flow through up to 20 capillaries belonging to a single MVU. Increases in plasma insulin and exercise/muscle contraction lead to recruitment of additional MVUs. Insulin also increases arteriolar vasomotion. Both mechanisms increase the endothelial surface area and therefore transendothelial transport of glucose, fatty acids (FAs) and insulin by specific transporters, present in high concentrations in the capillary endothelium. Future studies should quantify transporter concentration differences between healthy and at risk populations as they may limit nutrient supply and oxidation in muscle and impair glucose and lipid homeostasis. An important recent discovery is that VEGF‐B produced by skeletal muscle controls the expression of FA transporter proteins in the capillary endothelium and thus links endothelial FA uptake to the oxidative capacity of skeletal muscle, potentially preventing lipotoxic FA accumulation, the dominant cause of insulin resistance in muscle fibres.

Housing Vacancy and the Shrinking City: Trends and Policies in the UK and the City of Liverpool

In the context of the discourse around shrinking cities, the aim of the paper was to try and better understand and differentiate the various types and causes of urban housing vacancy and to ask whether policy responses including planning policies appropriately reflect this variety. The paper briefly discusses the issue of shrinking cities, before considering theoretical explanations for housing vacancy and examining the relationships between population change, housing vacancy and policy responses in the Liverpool conurbation. Conclusions are then drawn about the nature of housing vacancy and the effectiveness of policy responses.

Resistance training increases skeletal muscle oxidative capacity and net intramuscular triglyceride breakdown in type I and II fibres of sedentary males

What is the central question of this study? Recent research from our laboratory, supported by in vitro effects of perilipins, suggested that improvements in insulin sensitivity following endurance training are mechanistically linked to increases in muscle oxidative capacity, intramuscular triglyceride utilization during moderate endurance exercise and increases in the content of the lipid droplet‐associated perilipins 2 and 5. This study aimed to investigate whether these adaptations also occur in response to resistance training. What is the main finding and its importance? Six weeks of resistance training increased all the mentioned variables. These novel data suggest that improvements in muscle oxidative capacity and lipid metabolism contribute to the increase in insulin sensitivity following resistance training.

Quantitative immunofluorescence microscopy of subcellular GLUT4 distribution in human skeletal muscle: effects of endurance and sprint interval training.

Increases 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. vastus lateralis of 16 sedentary males in the overnight fasted state before and after 6 weeks of ET and SIT. An antibody was fully validated and used to show large (> 1 μm) and smaller (<1 μm) GLUT4‐containing clusters. The large clusters likely represent trans‐Golgi network stores and the smaller clusters endosomal stores and GLUT4 storage vesicles (GSVs). Density of GLUT4 clusters was higher at the fibre periphery especially in perinuclear regions. A less dense punctate distribution was seen in the rest of the muscle fibre. Total GLUT4 fluorescence intensity increased in type I and type II fibres following both ET and SIT. Large GLUT4 clusters increased in number and size in both type I and type II fibres, while the smaller clusters increased in size. The greatest increases in GLUT4 fluorescence intensity occurred within the 1 μm layer immediately adjacent to the PM. The increase in peripheral localisation and protein content of GLUT4 following ET and SIT is likely to contribute to the improvements in glucose homeostasis observed after both training modes.

Immunofluorescence microscopy to assess enzymes controlling nitric oxide availability and microvascular blood flow in muscle.

Please cite this paper as: Cocks M, Shepherd SO, Shaw CS, Achten J, Costa ML, Wagenmakers AJM. Immunofluorescence microscopy to assess enzymes controlling nitric oxide availability and microvascular blood flow in muscle. Microcirculation 19: 642–651, 2012.

The effect of different training modes on skeletal muscle microvascular density and endothelial enzymes controlling NO availability

It 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. As eNOS produces nitric oxide (NO) and NAD(P)Hoxidase produces superoxide anions (O2−, quenching NO) we propose that the eNOS/NAD(P)Hoxidase protein ratio is a marker of vasodilator capacity. The novel methods show that endurance training (ET) and high intensity interval training (HIT), generally regarded as a time‐efficient alternative to ET, increase eNOS protein content and the eNOS/NADP(H)oxidase protein ratio in previously sedentary lean and obese young men. Resistance exercise training had smaller but qualitatively similar effects. Western blot data of other laboratories suggest that endurance exercise training leads to similar changes in sedentary elderly men. Future research will be required to investigate the relative importance of other sources and tissues in the balance between NO and O2− production seen by the vascular smooth muscle layer of terminal arterioles.