Sune Dandanell

Effect of anti-inflammatory medication on the running-induced rise in patella tendon collagen synthesis in humans

NSAIDs are widely used in the treatment of inflammatory diseases as well as of tendon diseases associated with pain in sports and labor. However, the effect of NSAID intake, and thus blockade of PGE(2) production, on the tendon tissue adaptation is unknown. The purpose of the present study was to elucidate the possible effects of NSAID intake on healthy tendon collagen turnover in relation to a strenuous bout of endurance exercise. Fifteen healthy young men were randomly assigned into two experimental groups, with one group receiving indomethacin (oral 2 × 100 mg Confortid daily for 7 days; NSAID; n = 7) and a placebo group (n = 8). Both groups were exposed to a prolonged bout of running (36 km). The collagen synthesis NH₂-terminal propeptide of type I (PINP) and PGE₂ concentrations were measured before and 72 h following the run in the patella tendon by microdialysis. The peritendinous concentrations of PINP increased significantly in the placebo group as a result of the run, as shown previously. PGE₂ levels were significantly decreased 72 h after the run compared with basal levels in the subjects treated with NSAID and unchanged in the placebo group. The NSAID intake abolished the adaptive increase in collagen synthesis in the patella tendon found in the placebo group in response to the prolonged exercise (P < 0.05). The present study demonstrates that intake of NSAID decreased interstitial PGE₂ and abolished the exercise-induced adaptive increase in collagen synthesis in human tendons.

Exercise training increases skeletal muscle mitochondrial volume density by enlargement of existing mitochondria and not de novo biogenesis

(i) To determine whether exercise‐induced increases in muscle mitochondrial volume density (MitoVD) are related to enlargement of existing mitochondria or de novo biogenesis and (ii) to establish whether measures of mitochondrial‐specific enzymatic activities are valid biomarkers for exercise‐induced increases in MitoVD.

Effect of alterations in blood volume with bed rest on glucose tolerance.

Bed rest leads to rapid impairments in glucose tolerance. Plasma volume and thus dilution space for glucose are also reduced with bed rest, but the potential influence on glucose tolerance has not been investigated. Accordingly, the aim was to investigate whether bed rest-induced impairments in glucose tolerance are related to a concomitant reduction in plasma volume. This hypothesis was tested mechanistically by restoring plasma volume with albumin infusion after bed rest and parallel determination of glucose tolerance. Fifteen healthy volunteers (age 24 ± 3 yr, body mass index 23 ± 2 kg/m2, maximal oxygen uptake 44 ± 8 ml·min-1·kg-1; means ± SD) completed 4 days of strict bed rest. Glucose tolerance [oral glucose tolerance test (OGTT)] and plasma and blood volumes (carbon monoxide rebreathing) were assessed before and after 3 days of bed rest. On the fourth day of bed rest, plasma volume was restored by means of an albumin infusion prior to an OGTT. Plasma volume was reduced by 9.9 ± 3.0% on bed rest day 3 and area under the curve for OGTT was augmented by 55 ± 67%. However, no association (R2 = 0.09, P = 0.33) between these simultaneously occurring responses was found. While normalization of plasma volume by matched albumin administration (408 ± 104 ml) transiently decreased (P < 0.05) resting plasma glucose concentration (5.0 ± 0.4 to 4.8 ± 0.3 mmol/l), this did not restore glucose tolerance. Bed rest-induced alterations in dilution space may influence resting glucose values but do not affect area under the curve for OGTT.

Repeated lifestyle interventions lead to progressive weight loss: A retrospective review chart study

Aims: This study aimed to investigate whether repeated lifestyle interventions lead to progressive weight loss or to weight cycling. Methods: A retrospective review chart study with follow-up on 2120 participants (mean±SD age 36±15 years; body weight 116±28 kg; fat 43±6%). All had participated in one to four 11–12 week lifestyle interventions (residential weight loss programme, mixed activities). Weight loss was promoted through a hypocaloric diet (−500 to −700 kcal/day) and daily physical activity (1–3 hours/day). Primary outcomes were weight loss and change in body composition (bioimpedance measurements) after the intervention periods and at follow-up. Results: A total of 2120, 526, 139 and 47 people participated in one to four interventions with mean±SEM times from start to follow-up of 1.3±0.1, 2.9±0.2, 4.2±0.3 and 5.2±0.4 years respectively. Overall 50, 41, 18 and 11% of the participants were lost to follow-up after one to four interventions, respectively. The cumulated weight loss at follow-up increased with the number of interventions from one to four: 12.2±0.1, 15.9±0.7, 16.1±1.2 and 18.5±2.0 kg (p<0.001). The ratios between cumulated loss of fat and fat free mass after one to four interventions decreased with the number of interventions (2.4, 2.2, 2.1 and 1.4). Rates of weight loss during the interventions ranged from 0.70±0.06 to 1.06±0.01 kg/week and the maximum weight regain during the follow-up periods was 0.039±0.007 kg/week. Conclusions: Repeated relatively short lifestyle interventions in a selected and motivated group can be an efficient method for weight loss maintenance with only limited body weight cycling in the interim periods. However, the relationship between loss of fat and fat free mass might change in an unfavourable direction.

Maintaining a clinical weight loss after intensive lifestyle intervention is the key to cardiometabolic health

OBJECTIVEnIntensive lifestyle interventions (ILI) are criticised for ineffective obesity treatment because weight loss over time is modest and thus of limited clinical relevance. However, a subgroup (5-30%) maintains a clinical weight loss >10%, but it is not clear if cardiometabolic health follows this pattern. The aim was to study the effect of different magnitudes of weight loss maintenance after ILI on cardiometabolic health.nnnMETHODSnEighty out of 2420 former participants (age: 36±1, BMI: 38±1, (means ±SE)) in an 11-12-week ILI were recruited into 3 groups; clinical weight loss maintenance (>10% weight loss), moderate maintenance (1-10%), and weight regain based on weight loss at follow-up (5.3±0.4years). Weight loss during the ILI was achieved by increased physical activity and hypo-caloric diet. Dual X-ray Absorptiometry, blood sample, skeletal muscle biopsy and VO2max test were used to determine cardiometabolic health at follow-up.nnnRESULTSnAt follow-up, the clinical weight loss maintenance group scored better in the following variables compared to the other groups: BMI (31±1, 33±2, 43±2kg/m2), composition (34±2, 40±1, 49±1% fat), visceral adipose tissue (0.8±0.2, 1.7±0.5, 2.4±0.4kg), plasma triglycerides (0.8±0.2, 1.3±0.4, 1.6±0.3mmol/L), plasma glucose (4.9±0.1, 5.9±0.4, 5.9±0.1mmol/L), Hb1Ac (5.1±0.0, 5.6±0.2, 5.8±0.2%), protein content in skeletal muscle of GLUT4 (1.5±0.2, 0.9±0.1, 1.0±0.1 AU) and hexokinase II (1.6±0.2, 1.0±0.2, 0.7±0.1 AU), citrate synthase activity (155±6, 130±5, 113±5μmol/g/min) and VO2max (49±1, 43±1, 41±1mL/min/FFM) (p<0.05).nnnCONCLUSIONnCardiometabolic health is better in participants who have maintained >10% weight loss compared to moderate weight loss and weight regain.

Influence of maximal fat oxidation on long-term weight loss maintenance in humans

Impaired maximal fat oxidation has been linked to obesity and weight regain after weight loss. The aim was to investigate the relationship between maximal fat oxidation (MFO) and long-term weight loss maintenance. Eighty subjects [means (SD): age, 36(13) yrs; BMI, 38(1) kg/m2] were recruited from a total of 2,420 former participants of an 11- to 12-wk lifestyle intervention. Three groups were established based on percent weight loss at follow-up [5.3(3.3) yr]: clinical weight loss maintenance (CWL), >10% weight loss; moderate weight loss (MWL), 1-10% weight loss; and weight regain (WR). Body composition (dual X-ray absorptiometry) and fat oxidation (indirect calorimetry) during incremental exercise were measured at follow-up. Blood and a muscle biopsy were sampled. At follow-up, a U-shaped parabolic relationship between MFO and percent weight loss was observed (ru2009=u20090.448; P < 0.001). Overall differences between CWL, MWL, and WR were observed in MFO (mean [95% confidence interval], in g/min, respectively: 0.46 [0.41-0.52]; 0.32 [0.27-0.38]; 0.45 [0.38-0.51]; P = 0.002), maximal oxygen uptake (V̇o2max, in ml·min-1·FFM-1, respectively; 49 [46-51]; 43 [40-47]; 41 [39-44]; P = 0.007), HAD-activity (in µmol·g-1·min-1, respectively: 123 [113-133]; 104 [91-118]; 97 [88-105]; P < 0.001), muscle protein content of CD36 (in AU, respectively: 1.1 [1.0-1.2]; 0.9 [0.8-1.0]; 0.9 [0.8-0.9]; P = 0.008) and FABPpm (in AU, respectively, 1.0 [0.8-1.2]; 0.7 [0.5-0.8]; 0.7 [0.5-0.9]; P = 0.008), body fat (in %, respectively: 33 [29-38]; 42 [38-46]; 52 [49-55]; P < 0.001), and plasma triglycerides (in mM, respectively: 0.8 [0.7-1.0]; 1.3 [0.9-1.7]; 1.6 [1.0-2.1]; P = 0.013). CWL and WR both had higher MFO compared with MWL, but based on different mechanisms. CWL displayed higher V̇o2max and intramuscular capacity for fat oxidation, whereas abundance of lipids at whole-body level and in plasma was higher in WR.NEW & NOTEWORTHY Impaired maximal fat oxidation has been linked to obesity and weight regain after weight loss. Noteworthy, maximal fat oxidation was equally high after clinical weight loss maintenance and weight regain compared with moderate weight loss. A high maximal fat oxidation after clinical weight loss maintenance was related to higher maximal oxygen updake, content of key proteins involved in transport of lipids across the plasma membrane and β-oxidation. In contrast, a high maximal fat oxidation after weight regain was related to higher availability of lipids, i.e., general adiposity and plasma concentration of triglycerides.

Determination of the exercise intensity that elicits maximal fat oxidation in individuals with obesity

Maximal fat oxidation (MFO) and the exercise intensity that elicits MFO (FatMax) are commonly determined by indirect calorimetry during graded exercise tests in both obese and normal-weight individuals. However, no protocol has been validated in individuals with obesity. Thus, the aims were to develop a graded exercise protocol for determination of FatMax in individuals with obesity, and to test validity and inter-method reliability. Fat oxidation was assessed over a range of exercise intensities in 16 individuals (age: 28 (26-29) years; body mass index: 36 (35-38) kg·m-2; 95% confidence interval) on a cycle ergometer. The graded exercise protocol was validated against a short continuous exercise (SCE) protocol, in which FatMax was determined from fat oxidation at rest and during 10 min of continuous exercise at 35%, 50%, and 65% of maximal oxygen uptake. Intraclass and Pearson correlation coefficients between the protocols were 0.75 and 0.72 and within-subject coefficient of variation (CV) was 5 (3-7)%. A Bland-Altman plot revealed a bias of -3% points of maximal oxygen uptake (limits of agreement: -12 to 7). A tendency towards a systematic difference (p = 0.06) was observed, where FatMax occurred at 42 (40-44)% and 45 (43-47)% of maximal oxygen uptake with the graded and the SCE protocol, respectively. In conclusion, there was a high-excellent correlation and a low CV between the 2 protocols, suggesting that the graded exercise protocol has a high inter-method reliability. However, considerable intra-individual variation and a trend towards systematic difference between the protocols reveal that further optimization of the graded exercise protocol is needed to improve validity.

Correlates and predictors of obesity-specific quality of life of former participants of a residential intensive lifestyle intervention: Quality of Life

The aim of this study was to investigate the relationship between weight loss during and after a unique type of weight loss intervention, namely, a residential intensive lifestyle intervention (ILI), and participants obesity‐specific health‐related quality of life (HRQOL) several years after the intervention. In the residential ILI under investigation, participants attended a 10‐ to 12‐week long course away from their daily living environment, namely, at Ubberup Folk High School located in Denmark.

Relationship between volition, physical activity and weight loss maintenance: Study rationale, design, methods and baseline characteristics

Aims: To investigate the relationship between volition, physical activity and weight loss maintenance. Methods: We recruited 84 sedentary (maximal oxygen uptake: 25 ± 5 ml/min), overweight and obese (Body mass index (BMI) 38 ± 7 m/h2, fat 44 ± 7 %) women (n = 55) and men (n = 29) for an interdisciplinary prospective study with follow-up. The change in lifestyle and weight loss is promoted via a 3-month intensive lifestyle intervention at a private health school. The intervention consists of supervised training (1–3 hours/day), a healthy hypo-caloric diet (−500 to −700 kCal/day) and education in healthy lifestyle in classes/groups. The participants’ body weight and composition (Dual Energy X-ray absorptiometry), volitional skills (questionnaire), physical activity level (heart rate accelerometer/questionnaire) and maximal oxygen uptake (indirect calorimetry) are to be monitored before, after, and 3 and 12 months after the intervention. Results: At the 12-month follow-up, three different groups will be established: Clinical weight loss maintenance (> 10% weight loss from baseline), moderate weight loss maintenance (1–10% weight loss) and no weight loss (or weight regain). A linear mixed model analysis will be used to compare levels of volitional skills, physical activity and maximal oxygen uptake over time, between the three groups. Correlational analyses will be used to investigate possible associations between volition, maximal oxygen uptake, physical activity level and weight loss maintenance. Conclusions : If specific volitional skills are identified as predictors of adherence to physical activity and success in clinical weight loss maintenance, these can be trained in future intensive lifestyle interventions in order to optimize the success rate.

Determinants of maximal whole‐body fat oxidation in elite cross‐country skiers: Role of skeletal muscle mitochondria

Elite endurance athletes possess a high capacity for whole‐body maximal fat oxidation (MFO). The aim was to investigate the determinants of a high MFO in endurance athletes. The hypotheses were that augmented MFO in endurance athletes is related to concomitantly increments of skeletal muscle mitochondrial volume density (MitoVD) and mitochondrial fatty acid oxidation (FAOp), that is, quantitative mitochondrial adaptations as well as intrinsic FAOp per mitochondria, that is, qualitative adaptations. Eight competitive male cross‐country skiers and eight untrained controls were compared in the study. A graded exercise test was performed to determine MFO, the intensity where MFO occurs (FatMax), and V˙O2Max . Skeletal muscle biopsies were obtained to determine MitoVD (electron microscopy), FAOp, and OXPHOSp (high‐resolution respirometry). The following were higher (P < 0.05) in endurance athletes compared to controls: MFO (mean [95% confidence intervals]) (0.60 g/min [0.50‐0.70] vs 0.32 [0.24‐0.39]), FatMax (46% V˙O2Max [44‐47] vs 35 [34‐37]), V˙O2Max (71 mL/min/kg [69‐72] vs 48 [47‐49]), MitoVD (7.8% [7.2‐8.5] vs 6.0 [5.3‐6.8]), FAOp (34 pmol/s/mg muscle ww [27‐40] vs 21 [17‐25]), and OXPHOSp (108 pmol/s/mg muscle ww [104‐112] vs 69 [68‐71]). Intrinsic FAOp (4.0 pmol/s/mg muscle w.w/MitoVD [2.7‐5.3] vs 3.3 [2.7‐3.9]) and OXPHOSp (14 pmol/s/mg muscle ww/MitoVD [13‐15] vs 11 [10‐13]) were, however, similar in the endurance athletes and untrained controls. MFO and MitoVD correlated (r2 = 0.504, P < 0.05) in the endurance athletes. A strong correlation between MitoVD and MFO suggests that expansion of MitoVD might be rate‐limiting for MFO in the endurance athletes. In contrast, intrinsic mitochondrial changes were not associated with augmented MFO.