Brian P. Carson

Exercise intensity‐dependent regulation of peroxisome proliferator‐activated receptor γ coactivator‐1α mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle

Skeletal muscle contraction increases intracellular ATP turnover, calcium flux, and mechanical stress, initiating signal transduction pathways that modulate peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α)‐dependent transcriptional programmes. The purpose of this study was to determine if the intensity of exercise regulates PGC‐1α expression in human skeletal muscle, coincident with activation of signalling cascades known to regulate PGC‐1α transcription. Eight sedentary males expended 400 kcal (1674 kj) during a single bout of cycle ergometer exercise on two separate occasions at either 40% (LO) or 80% (HI) of . Skeletal muscle biopsies from the m. vastus lateralis were taken at rest and at +0, +3 and +19 h after exercise. Energy expenditure during exercise was similar between trials, but the high intensity bout was shorter in duration (LO, 69.9 ± 4.0 min; HI, 36.0 ± 2.2 min, P < 0.05) and had a higher rate of glycogen utilization (P < 0.05). PGC‐1α mRNA abundance increased in an intensity‐dependent manner +3 h after exercise (LO, 3.8‐fold; HI, 10.2‐fold, P < 0.05). AMP‐activated protein kinase (AMPK) (2.8‐fold, P < 0.05) and calcium/calmodulin‐dependent protein kinase II (CaMKII) phosphorylation (84%, P < 0.05) increased immediately after HI but not LO. p38 mitogen‐activated protein kinase (MAPK) phosphorylation increased after both trials (∼2.0‐fold, P < 0.05), but phosphorylation of the downstream transcription factor, activating transcription factor‐2 (ATF‐2), increased only after HI (2.4‐fold, P < 0.05). Cyclic‐AMP response element binding protein (CREB) phosphorylation was elevated at +3 h after both trials (∼80%, P < 0.05) and class IIa histone deacetylase (HDAC) phosphorylation increased only after HI (2.0‐fold, P < 0.05). In conclusion, exercise intensity regulates PGC‐1α mRNA abundance in human skeletal muscle in response to a single bout of exercise. This effect is mediated by differential activation of multiple signalling pathways, with ATF‐2 and HDAC phosphorylation proposed as key intensity‐dependent mediators.

Influence of acute exercise with and without carbohydrate replacement on postprandial lipid metabolism

Acute exercise, undertaken on the day before an oral fat tolerance test (OFTT), typically reduces postprandial triglycerides (TG) and increases high-density lipoprotein-cholesterol (HDL-C). However, the benefits of acute exercise may be overstated when studies do not account for compensatory changes in dietary intake. The objective of this study was to determine the influence of acute exercise, with and without carbohydrate (CHO) replacement, on postprandial lipid metabolism. Eight recreationally active young men underwent an OFTT on the morning after three experimental conditions: no exercise [control (Con)], prolonged exercise without CHO replacement (Ex-Def) and prolonged exercise with CHO replacement to restore CHO and energy balance (Ex-Bal). The exercise session in Ex-Def and Ex-Bal consisted of 90 min cycle ergometry at 70% peak oxygen uptake (Vo(2peak)) followed by 10 maximal 1-min sprints. CHO replacement was achieved using glucose solutions consumed at 0, 2, and 4 h postexercise. Muscle glycogen was 40 +/- 4% (P < 0.05) and 94 +/- 3% (P = 0.24) of Con values on the morning of the Ex-Def and Ex-Bal OFTT, respectively. Postprandial TG were 40 +/- 14% lower and postprandial HDL-C, free fatty acids, and 3-hydroxybutyrate were higher in Ex-Def compared with Con (P < 0.05). Most importantly, these exercise effects were not evident in Ex-Bal. Postprandial insulin and glucose and the homeostatic model assessment of insulin resistance (HOMA(IR)) were not significantly different across trials. There was no relation between the changes in postprandial TG and muscle glycogen across trials. In conclusion, the influence of acute exhaustive exercise on postprandial lipid metabolism is largely dependent on the associated CHO and energy deficit.

Insulin signaling regulates fatty acid catabolism at the level of CoA activation

The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG) catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS). We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis.

Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise

BackgroundMany of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects.MethodsUsing a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL).ResultsThe intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70–120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43–55 nm (medium) particle range. VLDL-TG in smaller particles (29–43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state.ConclusionsThese findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.

The Rab11 Effector Protein FIP1 Regulates Adiponectin Trafficking and Secretion

Adiponectin is an adipokine secreted by white adipocytes involved in regulating insulin sensitivity in peripheral tissues. Secretion of adiponectin in adipocytes relies on the endosomal system, however, the intracellular machinery involved in mediating adiponectin release is unknown. We have previously reported that intracellular adiponectin partially compartmentalizes with rab 5 and rab11, markers for the early/sorting and recycling compartments respectively. Here we have examined the role of several rab11 downstream effector proteins (rab11 FIPs) in regulating adiponectin trafficking and secretion. Overexpression of wild type rab11 FIP1, FIP3 and FIP5 decreased the amount of secreted adiponectin expressed in HEK293 cells, whereas overexpression of rab11 FIP2 or FIP4 had no effect. Furthermore shRNA-mediated depletion of FIP1 enhanced adiponectin release whereas knock down of FIP5 decreased adiponectin secretion. Knock down of FIP3 had no effect. In 3T3L1 adipocytes, endogenous FIP1 co-distributed intracellularly with endogenous adiponectin and FIP1 depletion enhanced adiponectin release without altering insulin-mediated trafficking of the glucose transporter Glut4. While adiponectin receptors internalized with transferrin receptors, there were no differences in transferrin receptor recycling between wild type and FIP1 depleted adipocytes. Consistent with its inhibitory role, FIP1 expression was decreased during adipocyte differentiation, by treatment with thiazolidinediones, and with increased BMI in humans. In contrast, FIP1 expression increased upon exposure of adipocytes to TNFα. In all, our findings identify FIP1 as a novel protein involved in the regulation of adiponectin trafficking and release.

Body Sensor Network based on Soft Polymer Sensors and Wireless Communications

Wireless communications is now completely pervasive, and already is used in many guises by people in everyday life. However until now, the information exchanged has been mainly standard electronic forms of standard data such as text, images, video. More recently, attention has been increasingly focused on sensor-based data, which presents rich new areas for applications and research, particularly in the area of life-logging applications. Thus, focus must shift to developing new and novel sensor layers to bridge this interface between the real world of the body and the digital world of communications. The easiest means to do this is with wearable sensors, but this in turn raises the issue of ‘comfortable’ body monitoring systems. If the “wearable” device is uncomfortable then user compliance will be greatly compromised. At present many conventional sensors are unsuitable for wearable body monitoring devices, however, in this paper, we present a prototype wearable device which was used and compared to an established non-wearable method for monitoring breathing frequency.

An in vivo microdialysis characterization of the transient changes in the interstitial dialysate concentration of metabolites and cytokines in human skeletal muscle in response to insertion of a microdialysis probe.

Skeletal muscle has recently been described as an endocrine organ, capable of releasing cytokines and regulators of metabolism. Microdialysis of the interstitial space of skeletal muscle enables analysis of the release of such cytokines. The purpose of this study was to determine the transient changes in concentration of metabolites and cytokines in human skeletal muscle in a 7h period following the insertion of a microdialysis probe. In total, sixteen microdialysis catheters were inserted into the vastus lateralis of male participants (age 26.2±1.35y, height 180.8±3.89cm, mass 83.9±3.86kg, BMI 25.7±0.87kgm(-2), body fat 26.1±3.0%). Serial samples were analyzed by micro-enzymatic and multiplexed immunoassay. Muscle interstitial glucose and lactate levels remained stable throughout, amino acid concentrations stabilized after 2.5h, however, insertion of a microdialysis catheter induced a 29-fold increase in peak IL-6 (p<0.001) and 35-fold increase in peak IL-8 concentrations (p<0.001) above basal levels 6h post insertion. In contrast to stable amino acid, glucose and lactate concentrations after 2h, commonly reported markers of tissue homeostasis in in vivo microdialysis, the multi-fold increase in IL-6 and IL-8 following insertion of a microdialysis catheter is indicative of a sustained disturbance of tissue homeostasis.

The Effect of Strength Training on Performance Indicators in Distance Runners.

Abstract Beattie, K, Carson, BP, Lyons, M, Rossiter, A, and Kenny, IC. The effect of strength training on performance indicators in distance runners. J Strength Cond Res 31(1): 9–23, 2017—Running economy (RE) and velocity at maximal oxygen uptake (VV[Combining Dot Above]O2max) are considered to be the best physiological performance indicators in elite distance runners. In addition to cardiovascular function, RE and VV[Combining Dot Above]O2max are partly dictated by neuromuscular factors. One technique to improve neuromuscular function in athletes is through strength training. The aim of this study was to investigate the effect of a 40-week strength training intervention on strength (maximal and reactive strength), VV[Combining Dot Above]O2max, economy, and body composition (body mass, fat, and lean mass) in competitive distance runners. Twenty competitive distance runners were divided into an intervention group (n = 11; 29.5 ± 10.0 years; 72.8 ± 6.6 kg; 1.83 ± 0.08 m) and a control group (n = 9; 27.4 ± 7.2 years; 70.2 ± 6.4 kg; 1.77 ± 0.04 m). During week 0, 20, and 40, each subject completed 3 assessments: physiology (V2 mmol·L−1 BLa, V2 mmol·L−1 BLa [blood lactate], V4 mmol·L−1 BLa, RE, VV[Combining Dot Above]O2max, V[Combining Dot Above]O2max), strength (1 repetition maximum back squat; countermovement jump and 0.3 m drop jump), and body composition (body mass, fat mass, overall lean, and leg lean). The intervention group showed significant improvements in maximal and reactive strength qualities, RE, and VV[Combining Dot Above]O2max, at weeks 20 (p ⩽ 0.05) and 40 (p ⩽ 0.05). The control group showed no significant changes at either time point. There were no significant changes in body composition variables between or within groups. This study demonstrates that 40 weeks of strength training can significantly improve maximal and reactive strength qualities, RE, and VV[Combining Dot Above]O2max, without concomitant hypertrophy, in competitive distance runners.

Simultaneous validation of five activity monitors for use in adult populations

Numerous cut‐points exist to measure physical activity by accelerometry. The ability to compare accelerometer findings from different devices from different locations may be advantageous to researchers. This study aimed to develop and validate cut‐points for 1.5, 3, and 6 METs in five activity monitors simultaneously. Fifty‐six participants (mean age=39.9 [±11.5] years) performed six activities while wearing a CosMED K4b2 and five activity monitors: activPAL3 Micro, activPAL, ActiGraph GT1M, ActiGraph wGT3X‐BT, and GENEActiv. Receiver operating characteristic curves and analysis were used to develop and validate cut‐points for the vertical axis counts (all activity monitors) and sum of the vector magnitude (ActiGraph wGT3X‐BT and GENEActiv) for 15 second (all devices) and 60 second (ActiGraph devices) epochs. A random coefficients statistical model was used to derive MET predictive equations for all activity monitors. Bland‐Altman plots examined the variability in device error. No 1.5 MET cut‐points were developed for the activPAL devices. All developed cut‐points had high levels of sensitivity and specificity. When cross‐validated in an independent group, high levels of sensitivity and specificity remained (≥77.4%, monitor and intensity dependent). The mean bias based on the Bland‐Altman plots ranged from −0.03 METs to 0.35 METs (monitor dependent). This is the first study to develop and validate cut‐points for five activity monitors simultaneously with high levels of sensitivity and specificity (≥77.4%). This is potentially a step toward cross‐comparison/harmonization of data; however, further validation in a free‐living environment is warranted.

The accuracy of the SenseWear Pro3 and the activPAL3 Micro devices for measurement of energy expenditure

Activity monitors such as the SenseWear Pro3 (SWP3) and the activPAL3 Micro (aP3M) are regularly used by researchers and practitioners to provide estimates of the metabolic cost (METs) of activities in free-living settings. The purpose of this study is to examine the accuracy of the MET predictions from the SWP3 and the aP3M compared to the criterion standard MET values from indirect calorimetry. Fifty-six participants (mean age: 39.9 (±11.5), 25M/31F) performed eight activities (four daily living, three ambulatory and one cycling), while simultaneously wearing a SWP3, aP3M and the Cosmed K4B2 (K4B2) mobile metabolic unit. Paired samples T-tests were used to examine differences between device predicted METs and criterion METs. Bland-Altman plots were constructed to examine the mean bias and limits of agreement for predicted METs compared to criterion METs. SWP3 predicted MET values were significantly different from the K4B2 for each activity (p  ⩽  0.004), excluding sweeping (p  =  0.122). aP3M predicted MET values were significantly different (p  <  0.001) from the K4B2 for each activity. When examining the activities collectively, both devices underestimated activity intensity (0.20 METs (SWP3), 0.95 METs (aP3M)). The greatest mean bias for the SWP3 was for cycling (-3.25 METs), with jogging (-5.16 METs) producing the greatest mean bias for the aP3M. All of the activities (excluding SWP3 sweeping) were significantly different from the criterion measure. Although the SWP3 predicted METs are more accurate than their aP3M equivalent, the predicted MET values from both devices are significantly different from the criterion measure for the majority of activities.