Ibuprofen does not impair skeletal muscle regeneration upon cardiotoxin-induced injury.

Muscle regeneration is regulated through interaction between muscle and immune cells. Studies showed that treatment with supra-physiological doses of Non-Steroidal Anti-Inflammatory Drug (NSAID) abolished inflammatory signaling and impaired muscle recovery. The present study examines the effects of pharmacologically-relevant NSAID treatment on muscle regeneration. C57BL/6 mice were injected in the tibialis anterior (TA) with either PBS or cardiotoxin (CTX). CTX-injected mice received ibuprofen (CTX-IBU) or were untreated (CTX-PLAC). After 2 days, Il-1beta and Il-6 expression was upregulated in the TA of CTX-IBU and CTX-PL vs. PBS. However, Cox-2 expression and macrophage infiltration were higher in CTX-PL vs. PBS, but not in CTX-IBU. At the same time, anabolic markers were higher in CTX-IBU vs. PBS, but not in CTX-PL. Nevertheless, ibuprofen did not affect muscle mass or muscle fiber regeneration. In conclusion, mild ibuprofen doses did not worsen muscle regeneration. There were even signs of a transient improvement in anabolic signaling and attenuation of inflammatory signaling.

Expression of lipolytic genes in adipose tissue is differentially regulated during multiple phases of dietary intervention in obese women.

The aim of this study was to investigate the time-course of the expression of key lipolysis-regulating genes in the subcutaneous adipose tissue (SCAT) during different phases of a 6-month dietary intervention. Fifteen obese women (BMI 34.7+/-1.0 kg.m(-2)) underwent a 6-month dietary intervention consisting of 1 month very low calorie diet (VLCD), followed by 2 months low calorie diet (LCD) and 3 months weight maintenance diet (WM). At each phase of the dietary intervention, a needle microbiopsy of the abdominal SCAT was obtained to evaluate mRNA expression of key lipolysis-regulating genes and a hyperinsulinemic euglycemic clamp (HEC) was performed. Dietary intervention induced a body weight reduction of 9.8 % and an improvement of insulin sensitivity as assessed by a HEC. Compared to pre-diet levels, mRNA levels of the adrenergic beta(2)-receptor in SCAT were higher at the end of VLCD and not different at the end of LCD and WM. In contrast, the expression of the adrenergic alpha(2)-receptor was lower at the end of VLCD and LCD compared to the pre-diet levels and did not differ at WM. Adipose triglyceride lipase and hormone-sensitive lipase levels were lower than the pre-diet levels at the end of LCD only, while phosphodiesterase-3B and the insulin receptor levels did not change throughout the dietary intervention. The results suggest that the regulation pattern of the genes that are involved in the control of lipolysis is different at the respective phases of the dietary intervention and depends on the duration of the diet and the status of energy balance.

Adrenaline but not noradrenaline is a determinant of exercise-induced lipid mobilization in human subcutaneous adipose tissue.

The relative contribution of noradrenaline (norepinephrine) and adrenaline (epinephrine) in the control of lipid mobilization in subcutaneous adipose tissue (SCAT) during exercise was evaluated in men treated with a somatostatin analogue, octreotide. Eight lean and eight obese young men matched for age and physical fitness performed 60 min exercise bouts at 50% of their maximal oxygen consumption on two occasions: (1) during i.v. infusion of octreotide, and (2) during placebo infusion. Lipolysis and local blood flow changes in SCAT were evaluated using in situ microdialysis. Infusion of octreotide suppressed plasma insulin and growth hormone levels at rest and during exercise. It blocked the exercise-induced increase in plasma adrenaline while that of noradrenaline was unchanged. Plasma natriuretic peptides (NPs) level was higher at rest and during exercise under octreotide infusion in lean men. Under placebo, no difference was found in the exercise-induced increase in glycerol between the probe perfused with Ringer solution alone and that with phentolamine (an alpha-adrenergic receptor antagonist) in lean subjects while a greater increase in glycerol was observed in the obese subjects. Under placebo, propranolol infusion in the probe containing phentolamine reduced by about 45% exercise-induced glycerol release; this effect was fully suppressed under octreotide infusion while noradrenaline was still elevated and exercise-induced lipid mobilization maintained in both lean and obese individuals. In conclusion, blockade of beta-adrenergic receptors during exercise performed during infusion of octreotide (blocking the exercise-induced rise in adrenaline but not that of noradrenaline) does not alter the exercise-induced lipolysis. This suggests that adrenaline is the main adrenergic agent contributing to exercise-induced lipolysis in SCAT. Moreover, it is the combined action of insulin suppression and NPs release which explains the lipolytic response which remains under octreotide after full local blockade of fat cell adrenergic receptors. For the moment, it is unknown if results apply specifically to SCAT and exercise only or if conclusions could be extended to all forms of lipolysis in humans.

Overshoot in VO2 following the onset of moderate-intensity cycle exercise in trained cyclists.

We have previously observed that following the onset of moderate intensity cycle ergometry, the pulmonary O2 uptake (VO2) in trained cyclists often does not increase towards its steady-state value with the typical mono-exponential characteristics; rather, there is a transient "overshoot". The purpose of this study was to systematically examine this phenomenon by comparing the VO2 responses to two moderate-intensity work rates and one high-intensity work rate in trained and untrained subjects. Following a ramp exercise test to the limit of tolerance for the determination of the gas exchange threshold (GET) and VO2(peak), seven trained cyclists [mean (SD); VO2(peak) 66.6 (2.5) ml x kg(-1) x min(-1)] and eight sedentary subjects [VO2(peak) 42.9 (5.1) ml x kg(-1) x min(-1)] completed six step transitions from baseline cycling to work rates requiring 60% and 80% GET and three step transitions from baseline cycling to a work rate requiring 50% of the difference between GET and VO2(peak) (50%delta). VO2 was measured breath-by-breath and modelled using standard techniques. The sedentary subjects did not overshoot the steady-state VO2 at any intensity. At 60% GET, six of the seven cyclists overshot the steady-state VO2 [by an integral volume of 164 (44) ml between approximately 45 and 125 s]. At 80% GET, four of the seven cyclists overshot the steady-state VO2 [by an integral volume of 185 (92) ml between approximately 55 and 140 s]. None of the cyclists showed an overshoot at 50%delta. These results indicate that trained cyclists evidence an overshoot in VO2 before steady-state is reached in the transition to moderate-intensity exercise. The mechanism(s) responsible for this effect remains to be elucidated, as does whether the overshoot confers any functional or performance benefit to the trained cyclist.

Effect of glycogen depletion on the oxygen uptake slow component in humans.

Previous studies have indicated that the (.-)VO(2) slow component is related to the recruitment of type II muscle fibres. We therefore hypothesised that an exercise and dietary regimen designed to deplete type I muscle fibres of glycogen would result in a greater contribution of type II muscle fibres to the exercise power output and therefore a larger amplitude of the (.-)VO(2) slow component. Eight male subjects took part in this study. On day 1, the subjects reported to the laboratory at 8 a.m., and completed a 9 min constant-load cycling test at a work rate equivalent to 85 % (.-)VO(2) peak. On day 2 at 12 p.m., the subjects were fed a 4200 kJ meal (60 % protein, 40 % fat); at 6 p.m. they completed a 2 h cycling test at 60 % (.-)VO(2) peak. On day 3 at 8 a.m., the subjects performed an exercise test identical to that of day 1. Metabolic and respiratory measurements indicated that our experimental design was effective in reducing the muscle glycogen content. (.-)VO(2) was significantly higher (by approximately 140 ml x min (-1)) throughout exercise following glycogen depletion but no appreciable changes in (.-)VO(2) kinetics were found: neither the time constant of the primary response (from 35.4 +/- 2.5 to 33.2 +/- 4.4 s) nor the amplitude of the slow component (from 404 +/- 95 to 376 +/- 81 ml x min (-1)) was significantly altered. Therefore, we suggest that the increased (.-)VO(2) throughout exercise and the unaltered (.-)VO(2) slow component following glycogen depletion might be explained by a shift towards a greater reliance on fat metabolism in type I muscle fibres with no appreciable change in fibre type recruitment patterns.

The decrease in VO(2) slow component induced by prior exercise does not affect the time to exhaustion.

In previous studies decreases in the VO(2) slow component were observed after prior heavy exercise. The observed effects after prior low-intensity exercise were rather controversial. The purpose of the present study was to more thoroughly examine the effects of prior low-intensity exercise on the VO(2) slow component. Furthermore, it has been suggested that the VO(2) slow component may be a determinant of exercise tolerance. Therefore we tested the hypothesis whether an attenuated VO(2) slow component induced by prior exercise could affect the time to exhaustion. Ten subjects performed four exercise protocols consisting of heavy cycling exercise (95 % VO(2)peak) until exhaustion. This constant-load exercise was performed without prior exercise (protocol NPE), or was preceded by 6 min heavy cycling exercise (protocol 6HPE), 12 min low-intensity cycling exercise (protocol 12LPE) or 6 min low-intensity cycling exercise (protocol 6LPE). The VO(2) slow component quantified as Delta VO(2 (end-2)) (669 +/- 90 ml x min (-1) in NPE) was significantly reduced after heavy as well as low-intensity exercise (respectively 47 %, 29 % and 17 % in 6HPE, 12LPE and 6LPE). This reduction lead to a significantly lower end VO(2) in 6HPE and 12LPE. The time to exhaustion (594 +/- 139 s in NPE), however, was unaffected by prior exercise rejecting our hypothesis that the attenuated VO(2) slow component could improve the capability to sustain exercise performance.

The effect of prior high-intensity cycling exercise on the VO2 kinetics during high-intensity cycling exercise is situated at the additional slow component.

In previous studies conclusions about the effect of prior exercise on VO2 kinetics of subsequent high-intensity exercise are generally based on observed changes in the overall VO2 response without considering the effects on the VO2 fast and slow component. The aim of the present study was to examine the effect on the VO2 fast and slow component separately. Therefore 10 subjects performed an exercise protocol consisting of an initial 3 min period of unloaded cycling followed by two constant-load work bouts at a work rate corresponding to 90% VO2peak, separated by 3 min of rest and 3 min of unloaded cycling. VO2 was measured on a breath-by-breath basis, and the response curves were analysed by a biexponential model. To increase signal-to-noise ratio, subjects performed four repetitions of the exercise protocol, each separated by at least one day. There was no significant alteration in VO2 kinetic parameters of the primary, fast component after high-intensity exercise. However, there was a significant effect of prior high-intensity exercise on the VO2 kinetic parameters of the slow component. The time constant and the amplitude of the slow component were reduced by respectively 44% (from 231.0 +/- 111.7 s to 130.1 +/- 50.4 s) and 49% (from 824 +/- 270 ml x min(-1) to 417 +/- 134 ml x min(-1)). The results of this study indicate that the effect of high-intensity exercise on the VO2 kinetics of a subsequent high-intensity exercise is probably limited to an effect on the slow component.

In humans the oxygen uptake slow component is reduced by prior exercise of high as well as low intensity.

The aim of the study was to examine to what extent prior high- or low-intensity cycling, yielding the same amount of external work, influenced the oxygen uptake (VO2) slow component of subsequent high-intensity cycling. The 12 subjects cycled in two protocols consisting of an initial 3 min period of unloaded cycling followed by two periods of constant-load exercise separated by 3 min of rest and 3 min of unloaded cycling. In protocol 1 both periods of exercise consisted of 6 min cycling at a work rate corresponding to 90% peak oxygen uptake (VO2peak). Protocol 2 differed from protocol 1 in that the first period of exercise consisted of a mean of 12.1 (SD 0.8) min cycling at a work rate corresponding to 50% VO2peak. The difference between the 3rd min VO2 and the end VO2 (deltaVO2(6-3)) was used as an index of the VO2 slow component. Prior high-intensity exercise significantly reduced deltaVO2(6-3). The deltaVO2(6-3) was also reduced by prior low-intensity exercise despite an unchanged plasma lactate concentration at the start of the second period of exercise. The reduction was more pronounced after prior high- than after prior low-intensity exercise (59% and 28%, respectively). The results of this study show that prior exercise of high as well as low intensity reduces the VO2 slow component and indicate that a metabolic acidosis is not a necessary condition to elicit a reduction in deltaVO2(6-3).