Gymnastik- och idrottshögskolan, GIH

max, separated by 30-min rest. All biomarkers were analysed in blood samples taken before and after cycling at each intensity. Increases in noradrenaline and lactate were related to increases in mBDNF-S, while increases in cortisol were related to increases in proBDNF. LAC-AV-B was related only to increases in circulating lactate. Changes in mBDNF-S were predicted by fCSA%-II, while increases in proBDNF were not. Exploratory analyses also revealed hypothesis-generating observations of a possible pattern of higher proBDNF levels in Val66Val carriers, whereas a trend toward greater increases in LAC-AV-B in Val66Met carriers. Finally, findings raise the possibility that catecholamine-related increases in mBDNF-S and cortisol-related increases in proBDNF may be linked to mechanisms previously associated with synaptic strengthening and pruning, respectively.

Brain-derived neurotrophic factor (BDNF) is essential for neuroplasticity. Exercise caninduce increases in forearm venous plasma and serum BDNF, often assumed to be indicativeof release from the brain. We investigated the effects of exercise on circulating levels of matureBDNF (mBDNF) and its precursor proBDNF. Sixteen healthy, physically fit adults (20–40 years old)cycled for 20 min at 40, 60 and 80% of V˙O2 max, separated by 30 min of rest. BDNF was analysed in blood samples from the brachial artery, internal jugular vein, femoral vein and antecubital vein. Brain/skeletal muscle exchange of BDNF, calculated as arterial-venous differences in BDNF multiplied by blood flow in the middle cerebral artery/common femoral artery, was measured simultaneously with blood sampling. Exercise intensity-dependent increases were observed in blood platelet count, forearm venous serum mBDNF and plasma proBDNF, but not in forearm venous plasma mBDNF. Brain release (or uptake) was not detected for either plasma mBDNF, serum mBDNF or plasma proBDNF. However, muscle uptake of plasma mBDNF and release of plasma proBDNF were observed after high-intensity exercise. Our findings demonstrate that exercise-dependent increases in serum mBDNF are not derived from the brain or the exercised skeletal muscle. Rather, the source of the increase appears to be the increase in platelets that are enriched with mBDNF. Furthermore, in physically fit adults, BDNF is not released from the brain into the bloodstream, after exercise, regardless of exercise intensity. Finally, changes in plasma proBDNF after exercise appear to be dependent on exercised skeletal muscle rather than brain release. KEY POINTS: Previously shown exercise-induced increases in forearm venous brain-derived neurotrophic factor (BDNF) are often assumed to be indicative of release from the brain. We investigated whether exercise-induced changes in forearm venous mature BDNF (mBDNF) and precursor proBDNF are paralleled by concomitant changes in BDNF exchange over the brain and skeletal muscle. We observed exercise intensity-dependent increases in platelet count, forearm venous serum mBDNF and plasma proBDNF, but not in forearm venous plasma mBDNF. We found muscle uptake of plasma mBDNF and release of plasma proBDNF after high-intensity exercise but no exercise intensity-dependent brain exchange of either plasma mBDNF, serum mBDNF or plasma proBDNF. Our findings suggest that acute exercise-induced increases in circulating serum mBDNF may be solely a result of increased platelet count, probably due to splenic platelet release; and that exercised skeletal muscle, and not the brain, responds to high-intensity exercise by releasing plasma proBDNF.

CONTEXT: Insulin resistance (IR) is a major risk factor for the development of several diseases that have reached epidemic proportions worldwide, including hypertension, obesity and type 2 diabetes. In many diseased states, IR is associated with fasting hyperinsulinemia/excessive glucose-stimulated insulin secretion. However, it is not known whether hyperinsulinemia precedes/leads to the natural development of IR or vice versa.

OBJECTIVE: Here, we assess the relationship between hyperinsulinemia and insulin sensitivity in a cohort of healthy young lean men and women, where IR is observed in those who exhibit a low expression of type I skeletal muscle fibers and a high resting heart rate.

METHODS: Biopsies were obtained from the vastus lateralis muscle, followed by an intravenous glucose tolerance test. Insulin secretion and whole-body insulin sensitivity were calculated.

RESULTS: In this young population of normoglycemic, glucose-tolerant individuals, insulin sensitivity was significantly and negatively associated with fasting levels of plasma insulin, as well as insulin secretion in response to glucose infusion. Surprisingly, however, all the correlations became stronger when calculated in women, but became insignificant when calculated in men. In contrast, insulin sensitivity was significantly correlated with expression of type I skeletal muscle fibers and resting heart rate to similar extents in both sexes.

CONCLUSIONS: In the natural development of IR in men, it appears that hyperinsulinemia is a compensatory adaptation to peripheral IR rather than its cause.

OBJECTIVE: Here we use skeletal muscle fiber composition to investigate whether defects in amino acid metabolism are involved in the early development of IR in healthy young individuals before onset of clinical manifestations.

DESIGN: Two groups consisting of healthy young men and women, insulin-sensitive and insulin resistant, were studied using a cross-sectional design.

METHODS: Biopsies were obtained from the vastus lateralis muscle and an intravenous glucose tolerance test was performed. Plasma and muscle tissue were analyzed by metabolomics.

RESULTS: Subjects in group 1 (n=20; age 28±5 yrs; body mass index 22.3±2.7 kg/m2) had an expression of type I muscle fibers and whole-body insulin sensitivity, respectively, of 58.8±5.7% and 1.8±0.7 units. Subjects in group 2 (n=16; age 25±6 yrs; body mass index 22.6±3.0 kg/m2) had an expression of type I muscle fibers and whole-body insulin sensitivity, respectively, of 29.8±6.6% and 0.8±0.3 units (P<0.001 vs. group 1 for both). Anserine and β-alanine contents in muscle were significantly higher and taurine lower in group 2 vs. 1, consistent with the differences in muscle fiber composition between groups. Taurine correlated well with insulin sensitivity and expression of type I muscle fibers (r=0.63; P<0.001 for both). In contrast, there were no significant differences in plasma or tissue contents of glutamine, arginine, or branch-chain amino acids between groups.

CONCLUSIONS: These data demonstrate that the early development of IR is not a consequence of defects in amino acid metabolism. Rather, defects in amino acid metabolism in diseased states are more likely a consequence of IR.

Insulin resistance (IR) is a risk factor for the development of several major metabolic diseases. Muscle fiber composition is established early in life and is associated with insulin sensitivity. Hence, muscle fiber composition was used to identify early defects in the development of IR in healthy young individuals in the absence of clinical manifestations. Biopsies were obtained from the thigh muscle, followed by an intravenous glucose tolerance test. Indices of insulin action were calculated and cardiovascular measurements, analyses of blood and muscle were performed. Whole-body insulin sensitivity (SI_galvin) was positively related to expression of type I muscle fibers (r=0.49; P<0.001) and negatively related to resting heart rate (HR, r=-0.39; P<0.001), which was also negatively related to expression of type I muscle fibers (r=-0.41; P<0.001). Muscle protein expression of endothelial nitric oxide synthase (eNOS), whose activation results in vasodilation, was measured in two subsets of subjects expressing a high percentage of type I fibers (59±6%; HR = 57±9 beats/min; SI_galvin = 1.8±0.7 units) or low percentage of type I fibers (30±6%; HR = 71±11; SI_galvin = 0.8±0.3 units; P<0.001 for all variables vs. first group). eNOS expression was: 1. higher in subjects with high type I expression; 2. almost two-fold higher in pools of type I vs. II fibers; 3. only detected in capillaries surrounding muscle fibers; and 4. linearly associated with SI_galvin. These data demonstrate that an altered function of the autonomic nervous system and a compromised capacity for vasodilation in the microvasculature occur early in the development of IR.

Aim

In adults, prolonged periods of sitting have been linked to acute negative effects on vascular structure and function. The aim of this study was to evaluate the acute effects of physical activity (PA) breaks during prolonged sitting on arterial stiffness, cortisol and psychological factors in adolescents.

Methods

Adolescents underwent different short (3-min) breaks starting every 20 min, during 80 min of sitting on three separate days. Breaks were (A) social seated breaks (SOC), (B) low-intensity simple resistance activity PA breaks (SRA) and (C) moderate-intensity step-up PA breaks (STEP). The arterial stiffness measures were augmentation index (AIx), AIx@75 and pulse wave velocity (PWV). Cortisol was measured from saliva. Psychological factors were self-reported.

Results

Eleven girls and six boys (average age 13.6 ± 0.7 years) participated, with average baseline heart rates of 72 ± 11 bpm, systolic/diastolic blood pressure 111 ± 7/64 ± 6 mmHg and cortisol 10.9 ± 5.8 nmoL/L. PWV, cortisol and psychological factors did not change after any of the conditions. AIx@75 increased significantly (4.9 ± 8.7–9.2 ± 13.2) after the STEP intervention compared with SOC and SRA (time × condition p < 0.05).

Conclusion

Arterial stiffness increased after prolonged sitting with frequent, short step-up activity breaks. The results indicate potential important intensity-dependent effects of physical activity on vascular regulation in youth.

There is a debate on whether lipid-mediated insulin resistance derives from an increased or decreased capacity of muscle to oxidize fats. Here we examine the involvement of muscle fiber composition in the metabolic responses to a 3-day fast (starvation, which results in increases in plasma lipids and insulin resistance) in two groups of healthy young subjects: 1, area occupied by type I fibers = 61.0 ± 11.8%; 2, type I area = 36.0 ± 4.9% (P<0.001). Muscle biopsies and intravenous glucose tolerance tests were performed after an overnight fast and after starvation. Biopsies were analyzed for muscle fiber composition and mitochondrial respiration. Indices of glucose tolerance and insulin sensitivity were determined. Glucose tolerance was similar in both groups after an overnight fast and deteriorated to a similar degree in both groups after starvation. In contrast, whole-body insulin sensitivity decreased markedly after starvation in group 1 (P<0.01), whereas the decrease in group 2 was substantially smaller (P=0.06). Non-esterified fatty acids and β-hydroxybutyrate levels in plasma after an overnight fast were similar between groups and increased markedly and comparably in both groups after starvation, demonstrating similar degrees of lipid load. The capacity of permeabilized muscle fibers to oxidize lipids was significantly higher in group 1 vs. 2, whereas there was no significant difference in pyruvate oxidation between groups. The data demonstrate that loss of whole-body insulin sensitivity after short-term starvation is a function of muscle fiber composition and is associated with an elevated rather than a diminished capacity of muscle to oxidize lipids.

Brain-derived neurotrophic factor (BDNF) and cortisol are both capable of modulating synaptic plasticity, but it is unknown how physical activity-induced changes in their plasma levels relate to corticospinal plasticity in humans. Sixteen inactive middle-aged men and women participated in three separate interventions consisting of 3hours prolonged sitting (SIT); 3hours sitting interrupted every 30minutes with frequent short physical activity breaks (FPA); and 2.5hours prolonged sitting followed by 25minutes of moderate intensity exercise (EXE). These 3hour sessions were each followed by a 30min period of paired associative stimulation over the primary motor cortex (PAS). Blood samples were taken and corticospinal excitability measured at baseline, pre PAS, 5min and 30min post PAS. Here we report levels of plasma BDNF and cortisol over three activity conditions and relate these levels to previously published changes in corticospinal excitability of a non-activated thumb muscle. There was no interaction between time and condition in BDNF, but cortisol levels were significantly higher after EXE compared to after SIT and FPA. Higher cortisol levels at pre PAS predicted larger increases in corticospinal excitability from baseline to all subsequent time points in the FPA condition only, while levels of BDNF at pre PAS did not predict such changes in any of the conditions. Neither BDNF nor cortisol modified changes from pre PAS to the subsequent time points, suggesting that the increased corticospinal excitability was not mediated though an augmented effect of the PAS protocol. The relationship between cortisol and plasticity has been suggested to be U-shaped. This is possibly why the moderately high levels of cortisol seen in the FPA condition were positively associated with changes AURC, while the higher cortisol levels seen after EXE were not. A better understanding of the mechanisms for how feasible physical activity breaks affect neuroplasticity can inform the theoretical framework for how work environments and schedules should be designed. DATA AVAILABILITY: Data are available from the corresponding author upon reasonable request.

CONTEXT: Muscle fiber composition is associated with peripheral insulin action.

OBJECTIVE: We investigated whether extreme differences in muscle fiber composition are associated with alterations in peripheral insulin action and secretion in young, healthy subjects who exhibit normal fasting glycemia and insulinemia.

METHODS: Relaxation time following a tetanic contraction was used to identify subjects with a high or low expression of type I muscle fibers: group I (n=11), area occupied by type I muscle fibers = 61.0 ± 11.8%; group II (n=8), type I area = 36.0 ± 4.9% (P<0.001). Biopsies were obtained from the vastus lateralis muscle and analyzed for mitochondrial respiration on permeabilized fibers, muscle fiber composition and capillary density. An intravenous glucose tolerance test was performed and indices of glucose tolerance, insulin sensitivity and secretion were determined.

RESULTS: Glucose tolerance was similar between groups, whereas whole-body insulin sensitivity was decreased by ~50% in group II vs group I (P=0.019). First phase insulin release (area under the insulin curve during 10 min after glucose infusion) was increased by almost 4-fold in group II vs I (P=0.01). Whole-body insulin sensitivity was correlated with % area occupied by type I fibers (r=0.54; P=0.018) and capillary density in muscle (r=0.61; P=0.005), but not with mitochondrial respiration. Insulin release was strongly related to % area occupied by type II fibers (r=0.93; P<0.001).

CONCLUSIONS: Assessment of muscle contractile function in young healthy subjects may prove useful in identifying individuals with insulin resistance and enhanced glucose stimulated insulin secretion prior to onset of clinical manifestations.