Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial.

BACKGROUND: Identifying and reducing cardiometabolic risks driven by obesity remains a healthcare challenge. The metabolic syndrome is associated with abdominal obesity and inflammation and is predictive of long-term risk of developing type 2 diabetes and cardiovascular disease in otherwise healthy individuals living with obesity. Therefore, we investigated the effects of adherent exercise, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), or the combination on severity of metabolic syndrome, abdominal obesity, and inflammation following weight loss. METHODS: This was a randomized, double-blinded, placebo-controlled trial. During an 8-week low-calorie diet (800 kcal/day), 195 adults with obesity and without diabetes lost 12% in body weight. Participants were then evenly randomized to four arms of one-year treatment with: placebo, moderate-to-vigorous exercise (minimum of 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity aerobic physical activity or an equivalent combination of both), the GLP-1 RA liraglutide 3.0 mg/day, or a combination (exercise + liraglutide). A total of 166 participants completed the trial. We assessed the prespecified secondary outcome metabolic syndrome severity z-score (MetS-Z), abdominal obesity (estimated as android fat via dual-energy X-ray absorptiometry), and inflammation marker high-sensitivity C-reactive protein (hsCRP). Statistical analysis was performed on 130 participants adherent to the study interventions (per-protocol population) using a mixed linear model. RESULTS: The diet-induced weight loss decreased the severity of MetS-Z from 0.57 to 0.06, which was maintained in the placebo and exercise groups after one year. MetS-Z was further decreased by liraglutide (- 0.37, 95% CI - 0.58 to - 0.16, P < 0.001) and the combination treatment (- 0.48, 95% CI - 0.70 to - 0.25, P < 0.001) compared to placebo. Abdominal fat percentage decreased by 2.6, 2.8, and 6.1 percentage points in the exercise, liraglutide, and combination groups compared to placebo, respectively, and hsCRP decreased only in the combination group compared with placebo (by 43%, P = 0.03). CONCLUSION: The combination of adherent exercise and liraglutide treatment reduced metabolic syndrome severity, abdominal obesity, and inflammation and may therefore reduce cardiometabolic risk more than the individual treatments. Trial registration EudraCT number: 2015-005585-32, ClinicalTrials.gov: NCT04122716.

Effects of acute exercise and exercise training on plasma GDF15 concentrations and associations with appetite and cardiometabolic health in individuals with overweight or obesity - A secondary analysis of a randomized controlled trial.

Growth Differentiation Factor 15 (GDF15) is seemingly involved in appetite control. Acute exercise increases GDF15 concentrations in lean humans, but acute and long-term effects of exercise on GDF15 in individuals with overweight/obesity are unknown. We investigated the effects of acute exercise and exercise training on GDF15 concentrations in individuals with overweight/obesity and associations with appetite and cardiometabolic markers. 90 physically inactive adults (20-45 years) with overweight/obesity were randomized to 6-months habitual lifestyle (CON, n=16), or isocaloric exercise of moderate (MOD, n=37) or vigorous intensity (VIG, n=37), 5 days/week. Testing was performed at baseline, 3, and 6 months. Plasma GDF15 concentrations, other metabolic markers, and subjective appetite were assessed fasted and in response to acute exercise before an ad libitum meal. Cardiorespiratory fitness, body composition, insulin sensitivity, and intraabdominal adipose tissue were measured. At baseline, GDF15 increased 18% (95%CI: 4; 34) immediately after acute exercise and 32% (16; 50) 60 min post-exercise. Fasting GDF15 increased 21% (0; 46) in VIG after 3 months (p=0.045), but this attenuated at 6 months (13% (-11; 43), p=0.316) and was unchanged in MOD (11% (-6; 32), p=0.224, across 3 and 6 months). Post-exercise GDF15 did not change in MOD or VIG. GDF15 was not associated with appetite or energy intake. Higher GDF15 was associated with lower cardiorespiratory fitness, central obesity, dyslipidemia, and poorer glycemic control. In conclusion, GDF15 increased in response to acute exercise but was unaffected by exercise training. Higher GDF15 concentrations were associated with a less favorable cardiometabolic profile but not with markers of appetite. This suggests that GDF15 increases in response to acute exercise independent of training state. Whether this has an impact on free-living energy intake and body weight management needs investigation.

Extreme duration exercise affects old and younger men differently.

AIM & METHODS: Extreme endurance exercise provides a valuable research model for understanding the adaptive metabolic response of older and younger individuals to intense physical activity. Here, we compare a wide range of metabolic and physiologic parameters in two cohorts of seven trained men, age 30 ± 5 years or age 65 ± 6 years, before and after the participants travelled ≈3000 km by bicycle over 15 days. RESULTS: Over the 15-day exercise intervention, participants lost 2-3 kg fat mass with no significant change in body weight. V̇O2 max did not change in younger cyclists, but decreased (p = 0.06) in the older cohort. The resting plasma FFA concentration decreased markedly in both groups, and plasma glucose increased in the younger group. In the older cohort, plasma LDL-cholesterol and plasma triglyceride decreased. In skeletal muscle, fat transporters CD36 and FABPm remained unchanged. The glucose handling proteins GLUT4 and SNAP23 increased in both groups. Mitochondrial ROS production decreased in both groups, and ADP sensitivity increased in skeletal muscle in the older but not in the younger cohort. CONCLUSION: In summary, these data suggest that older but not younger individuals experience a negative adaptive response affecting cardiovascular function in response to extreme endurance exercise, while a positive response to the same exercise intervention is observed in peripheral tissues in younger and older men. The results also suggest that the adaptive thresholds differ in younger and old men, and this difference primarily affects central cardiovascular functions in older men after extreme endurance exercise.

Effect of exercise training on skeletal muscle protein expression in relation to insulin sensitivity: Per-protocol analysis of a randomized controlled trial (GO-ACTIWE).

Exercise training improves peripheral insulin sensitivity and leads to molecular adaptations in the skeletal muscle. We investigated changes in the expression of key muscle proteins in the glucose metabolic pathway following active commuting by bike or leisure-time exercise at two different intensities. In addition, potential associations between insulin sensitivity and muscle protein expression were examined. This per-protocol analysis included 72 out of 130 physically inactive, healthy women and men (20-45 years) with overweight/obesity (BMI: 25-35 kg/m2 ) who completed 6 months of no intervention (CON, n = 12), active commuting by bike (BIKE, n = 14), or leisure-time exercise of moderate (MOD, n = 28) or vigorous (VIG, n = 18) intensity. Exercise was prescribed 5 days/week with a weekly exercise energy expenditure of 1,600 kcal for women and 2,100 kcal for men. Insulin sensitivity was determined by a hyperinsulinemic euglycemic clamp and skeletal muscle biopsies were obtained from m. vastus lateralis and analyzed for protein expression at baseline and after 3 and 6 months of intervention. We found an increased expression of pyruvate dehydrogenase (PDH) in the exercise groups compared with the control group following 6 months of training. No differential effects were observed on the protein expression following moderate versus vigorous intensity exercise. In addition, we found a positive association between insulin sensitivity and the expression of glucose transporter type 4 as well as PDH. The positive association and the increase in expression of PDH after exercise training points toward a role for PDH in the training-induced enhancement of insulin sensitivity.

Structured exercise alters the gut microbiota in humans with overweight and obesity-A randomized controlled trial.

OBJECTIVES: Studies suggest that exercise affects the composition and function of the human gut microbiota, yet this has not been investigated in a randomized controlled trial. The primary aim of this study was to assess if exercise alters the diversity, composition and functional potential of the gut microbiota in free-living humans. A secondary aim was to test whether alpha diversity was associated with phenotypical outcomes. METHODS: Eighty eight participants with overweight or obesity completed a 6-month randomized controlled trial with 4 arms; habitual living (CON), active commuting by bike (BIKE) and leisure-time exercise of moderate (MOD) or vigorous intensity (VIG). Faecal samples for 16 s rRNA gene amplicon sequencing were collected prior to randomization and again after 3 and 6 months, with simultaneous registration of phenotypical outcomes and diet. RESULTS: Shannon's diversity index increased by 5% in VIG (CI95 1-9%, P = 0.012) at 3 months compared with CON. No associations were observed between alpha diversity and phenotypical outcomes. Beta diversity changed in all exercise groups compared with CON, particularly the participants in VIG showed decreased heterogeneity. No genera changed significantly. The inferred functional potential of the microbiota in the exercise groups was increased, primarily at 3 months and in MOD. CONCLUSION: Structured exercise induced subtle changes to the human gut microbiota. Cardiorespiratory fitness and fat mass were not associated with alpha diversity.

Protocol for a randomised controlled trial of the combined effects of the GLP-1 receptor agonist liraglutide and exercise on maintenance of weight loss and health after a very low-calorie diet.

INTRODUCTION: The success rate of weight loss maintenance is limited. Therefore, the purpose of this study is to investigate the maintenance of weight loss and immunometabolic health outcomes after diet-induced weight loss followed by 1-year treatment with a glucagon-like peptide-1 receptor agonist (liraglutide), physical exercise or the combination of both treatments as compared with placebo in individuals with obesity. METHODS AND ANALYSIS: This is an investigator-initiated, randomised, placebo-controlled, parallel group trial. We will enrol expectedly 200 women and men (age 18-65 years) with obesity (body mass index 32-43 kg/m2) to adhere to a very low-calorie diet (800 kcal/day) for 8 weeks in order to lose at least 5% of body weight. Subsequently, participants will be randomised in a 1:1:1:1 ratio to one of four study groups for 52 weeks: (1) placebo, (2) exercise 150 min/week+placebo, (3) liraglutide 3.0 mg/day and (4) exercise 150 min/week+liraglutide 3.0 mg/day. The primary endpoint is change in body weight from randomisation to end-of-treatment. ETHICS AND DISSEMINATION: The trial has been approved by the ethical committee of the Capital Region of Denmark and the Danish Medicines Agency. The trial will be conducted in agreement with the Declaration of Helsinki and monitored to follow the guidelines for good clinical practice. Results will be submitted for publication in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: 2015-005585-32.

Effects of Exercise Domain and Intensity on Sleep in Women and Men with Overweight and Obesity.

Inadequate sleep is associated with cardiometabolic risk and adiposity. Exercise has been suggested as an efficient strategy to improve sleep; however, the effects of different types of exercise on sleep in individuals with overweight and obesity are not well understood. We examined effects of active commuting and leisure-time exercise on sleep in individuals with overweight or obesity. 130 physically inactive adults (20-45 years) with overweight or class 1 obesity (body mass index: 25-35 kg/m2) were randomized to 6 months of habitual lifestyle (CON, n = 18), active commuting by bike (BIKE, n = 35), or leisure-time exercise of moderate intensity (MOD, 50% VO2peak-reserve, n = 39) or vigorous intensity (VIG, 70% VO2peak-reserve, n = 38), 5 days/week. Sleep was assessed from 7-day/night accelerometry and questionnaires at baseline, 3 months, and 6 months. 92 participants were included in a per protocol analysis. At 3 months, sleep duration was longer in VIG (29 min/night [3; 55] (mean [95% CI]), p=0.03) but not in BIKE and MOD (p ≥ 0.11) compared with CON and was not different between groups at 6 months (p ≥ 0.36 vs. CON). At 6 months, sleep duration variability was lower in MOD (-31% [-50; -3], p=0.03) and numerically lower in VIG (-28% [-49; 1], p=0.06) relative to CON but was unchanged in BIKE (p=0.17 vs. CON). The effects were, however, primarily attributable to shorter and more irregular sleep in CON over time. Our findings suggest that effects of exercise on sleep in individuals with overweight and obesity may be restricted to leisure-time exercise with a short-term effect on sleep duration after vigorous intensity exercise (3 months) but a more regular sleep pattern after 6 months of moderate and vigorous intensity exercise compared with physically inactive controls. This trial was registered at clinicaltrials.gov with ID NCT01962259.

PPARG Pro12Ala Ala carriers exhibit greater improvements in peripheral insulin sensitivity in response to 12 weeks of aerobic exercise training.

The Ala allele of PPARG Pro12Ala ( rs1801282 ) is associated with greater improvements to the glucose metabolism in exercise studies, but whether this extends to peripheral insulin sensitivity is unknown. Our objective was to investigate the effect of PPARG Pro12Ala on exercise-induced changes in peripheral insulin sensitivity. A total of 124 (91 Pro homozygotes and 33 Ala carriers) previously physically inactive healthy young men and women with overweight or class 1 obesity who completed a 12 wk aerobic exercise intervention were included in the analysis. All participants underwent a hyperinsulinemic euglycemic clamp before and after the 12 wk intervention. The prescribed exercise frequency was 5-7 days/wk, and the exercise energy expenditure was 2,100 4,200 kcal/wk for men and 1,600 kcal/wk for women. Insulin sensitivity improved significantly in both genotype groups. However, Ala carriers had a 1.13-fold (95% confidence interval 1.01; 1.26, P = 0.032) greater improvement in insulin sensitivity from baseline compared with Pro homozygotes. Our data support that PPARG Pro12Ala modifies the effect of aerobic exercise on peripheral insulin sensitivity.

How does 6 months of active bike commuting or leisure-time exercise affect insulin sensitivity, cardiorespiratory fitness and intra-abdominal fat? A randomised controlled trial in individuals with overweight and obesity.

OBJECTIVES: To evaluate effects of active bike commuting or leisure-time exercise of two intensities on peripheral insulin sensitivity (primary outcome), cardiorespiratory fitness and intra-abdominal adipose tissue mass (secondary outcomes). METHODS: 188 physically inactive, healthy women and men (20-45 years) with overweight or class 1 obesity were recruited. In the 6-month trial, 130 participants were randomised to either: no intervention (CON), active commuting (BIKE) or leisure-time exercise of moderate (MOD, 50% VO2peak) or vigorous (VIG, 70% VO2peak) intensity. 100 completed follow-up testing. Exercise prescription was 5 days/week with a weekly exercise energy expenditure of 1600 kcal for women and 2100 kcal for men. Testing was performed at baseline, 3 months and 6 months. RESULTS: Peripheral insulin sensitivity (ml/min/pmol insulin/L) increased (improved) by 24% (95% CI 6% to 46%, p=0.01) in VIG compared with CON at 3 months. Peripheral insulin sensitivity increased (improved) by 20% in BIKE (95% CI 1% to 43%, p=0.04) and 26% in VIG (95% CI 7% to 47%, p<0.01) compared with CON at 6 months. Cardiorespiratory fitness increased in all exercise groups compared with CON at 6 months; but the increase was higher in those that undertook vigorous exercise than those who did moderate exercise. Intra-abdominal adipose tissue mass diminished across all exercise groups in comparison to CON at 6 months. CONCLUSIONS: Active bike commuting improved cardiometabolic health; as did leisure-time exercise. Leisure-time exercise of vigorous intensity conferred more rapid effects on peripheral insulin sensitivity as well as additional effects on cardiorespiratory fitness than did moderate intensity exercise. TRIAL REGISTRATION: NCT01962259.

Effects of active commuting and leisure-time exercise on appetite in individuals with overweight and obesity.

Acute exercise is associated with a transient suppression of appetite. The effects of regular exercise on appetite are not well understood. We aimed to determine the effects of active commuting and leisure-time exercise on appetite. One hundred thirty physically inactive women and men (20-45 yr) with overweight and obesity were randomized to 6 mo of habitual lifestyle (CON, n = 18), active commuting (BIKE, n = 35), or leisure-time exercise of moderate [MOD, 50% peak oxygen uptake (V̇o2peak)-reserve, n = 39] or vigorous (VIG, 70% V̇o2peak-reserve, n = 38) intensity. Appetite ratings, acylated ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and glucagon were assessed in the basal state and in response to meal and exercise challenges at baseline and 3 and 6 mo. Ad libitum energy intake was determined during test meals. Data from 90 participants (per protocol) were available, and results are comparisons with CON. At 3 mo, ad libitum energy intake was lower in VIG (-22%, P < 0.01), basal glucagon was lower in BIKE ( P < 0.05) and VIG ( P = 0.01), and postprandial ratings of prospective food consumption were lower in MOD ( P = 0.02) and VIG ( P < 0.001). In VIG, ratings of hunger ( P = 0.01) and prospective food consumption ( P = 0.03) were lower after acute exercise at 3 mo. At 6 mo, basal and postprandial GLP-1 were higher ( P ≤ 0.04) whereas postexercise PYY was lower ( P = 0.03) in VIG and postexercise CCK was lower in BIKE ( P = 0.03). Vigorous-intensity exercise training leads to a transient suppression of energy intake and subjective appetite (3 mo) but a more long-term increase in basal and postprandial GLP-1 (6 mo) in individuals with overweight and obesity. NEW & NOTEWORTHY This is the first randomized controlled trial, to our knowledge, investigating long-term effects of exercise domain and intensity on subjective and hormonal markers of appetite and ad libitum energy intake in individuals with overweight and obesity. Appetite was assessed in response to meal and exercise challenges at baseline and at 3 and 6 mo. Anorexigenic effects of exercise vary with the duration of intervention and are restricted to regular leisure-time exercise of vigorous intensity in individuals with overweight and obesity.

Effects of 6 Months of Active Commuting and Leisure-Time Exercise on Fibrin Turnover in Sedentary Individuals with Overweight and Obesity: A Randomised Controlled Trial.

Obesity and exercise constitute important factors for cardiovascular disease risk, but the long-term effects of different exercise modalities on haemostatic biomarkers are not well elucidated. We investigated the effects of 6 months of active commuting or leisure-time exercise on measures of fibrin turnover in individuals who are overweight and obese. Ninety younger (20-40 years), sedentary, healthy women and men who are overweight and obese (BMI: 25-35 kg/m2) were randomised to 6 months of habitual lifestyle (CON, n=16), active commuting (BIKE, n=19), or leisure-time exercise of moderate (MOD, ∼50% VO2peak reserve, n=31) or vigorous intensity (VIG, ∼70% VO2peak reserve, n=24). Fasting blood samples (baseline and 3 and 6 months) were analysed for cholesterols and triglycerides, thrombin generation, prothrombin fragment 1 + 2, D-dimer, fibrin clot properties, and fibrinolytic activity. We observed no differences between CON, BIKE, MOD, and VIG during the intervention and no time effects for any of the variables measured despite increased VO2peak in all exercise groups. We found no difference between CON and all exercise groups combined and no gender-specific effects of exercise. Our findings suggest that thrombin generation capacity, coagulation activation, fibrin clot structure, and lysability are unaffected by long-term active commuting and leisure-time exercise in women and men who are overweight and obese.

2706 km cycling in 2 weeks: effects on cardiac function in 6 elderly male athletes.

OBJECTIVES: Physiological effects of exercise on trained and untrained individuals have been studied extensively. Typically, young or middle-aged individuals are examined before and after short periods of vigorous exertion. METHODS: We studied 6 elderly male athletes (61 ± 8 years (mean ± SD); baseline [Formula: see text]O2max 48 ± 5 ml·kg-1·min-1) with focus on cardiac function and biomarkers following 14 consecutive days of moderate intensity exercise. Cardiac dimensions, function, biomarkers, and other measures of cardiovascular health were examined at baseline and 2 and 28 h after the last day of cycling a total of 2706 km. RESULTS: Data collected after the cessation of exercise on the 14th day revealed significant increases in average size of the left atrium (3.5 ± 0.4 to 4.0 ± 0.3 cm; p = 0.02) and left ventricular end systolic volume (47 ± 2 to 52 ± 5 ml; p = 0.004), with no other significant changes in cardiac size or function. Small, transient increases in cardiac biomarkers (troponin T, creatine kinase myocardial band, and N-terminal pro-brain natriuretic peptide) (p < 0.01) were observed 2 h after completion of cycling but no changes in systolic (including strain-analyses) or diastolic cardiac function were observed at rest. [Formula: see text]O2max was significantly lower at the 28 h time point than at baseline (p < 0.02). Plasma concentrations of total- (p < 0.01) and low-density lipoprotein-cholesterol (p < 0.01) were markedly lower after exercise. Systolic blood pressure was unchanged, but diastolic pressure was significantly lower after exercise than at baseline. CONCLUSIONS: The results suggest that repeated moderate intensity exercise in elderly men was associated with a transient increase in cardiac biomarkers while cardiac function remained unaltered. A favorable reduction in blood lipids and diastolic blood pressure were seen for >28 h after the end of activity. An unexplained symptomless severe plasma hyponatremia developed in 3 of 6 subjects 28 h after the end of activity.

Exercise and weight loss effects on cardiovascular risk factors in overweight men.

Both exercise training and weight loss reduce cardiovascular risk, but the independent importance of the two strategies is unclear. We aimed to investigate independent and combined effects of exercise training and weight loss on lipoproteins and dyslipidemia in overweight sedentary men. Sixty individuals were randomized to 12 wk of endurance training (T), energy-reduced diet (D), training and energy increased diet (T-iD), or control (C). Equal energetic deficits (-600 kcal/day) were prescribed by exercise for T and caloric restriction for D. T-iD completed similar exercise but remained in energy balance due to the dietary replacement of calories expended during exercise. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo)B and A1, pre-ß-HDL, and susceptibility of LDL-C to oxidation were measured. Body weight was reduced similarly between T (-5.9 ± 0.7 kg) and D (-5.2 ± 0.8 kg), whereas T-iD (-1.0 ± 0.5 kg) and C (0.1 ± 0.6 kg) remained weight stable. Plasma TC, LDL-C, and apolipoprotein B were reduced in T compared with C ( P < 0.001 for both), but this was not observed for D ( P > 0.17). Changes in TC and LDL-C were associated with changes in body weight and body fat ( P < 0.01). In T-iD, increases in HDL-C and apolipoprotein A1 were observed ( P < 0.001). In conclusion, an exercise-induced decline in body weight reduces proatherogenic apoB-containing lipoproteins, whereas exercise compensated by energy intake increases the key component of reverse cholesterol transport, i.e., apoA1-containing HDL-C. NEW & NOTEWORTHY Exercise has additive effects in lowering plasma lipoprotein particles to diet-induced weight loss in individuals with increased cardiovascular risk. In the present study, we investigated whether training per se would have beneficial cardiovascular effects. We found that 3 mo of exercise-induced weight loss reduced proatherogenic lipoproteins, whereas endurance training without weight loss improved factors involved in reverse cholesterol transport in a group of overweight sedentary men.

Repeated Excessive Exercise Attenuates the Anti-Inflammatory Effects of Exercise in Older Men.

Introduction/Purpose: A number of studies have investigated the effect of training with a moderate exercise dose (3-6 h/weekly) on the inflammatory profile in blood, and the data are inconsistent. Cross-sectional studies indicate a positive effect of physical activity level on inflammation levels and risk of metabolic disease. However, it is not clear whether this may be dose dependent and if very prolonged repeated exercise therefore may be beneficial for low-grade inflammation. Based on this we studied how excessive repeated prolonged exercise influenced low-grade inflammation and adipose tissue anti-inflammatory macrophage content in six older male recreationally trained cyclists. Low-grade inflammation and adipose tissue macrophage content were investigated in six older trained men (age: 61 ± 4 years; VO2peak: 48 ± 2 mL kg-1 min-1) following repeated prolonged exercise. Methods: Cycling was performed daily for 14 days covering in total 2,706 km (1,681 miles). Maximal oxygen uptake (VO2peak) was measured before and after the cycling. Duration and intensity of the exercise were determined from heart rates sampled during cycling. An adipose tissue biopsy from subcutaneous abdominal fat and a blood sample were obtained at rest in the overnight fasted state before and after the cycling. Anti-inflammatory adipose tissue macrophages (ATM) were immunohistochemically stained in cross sectional sections using a CD163 binding antibody. The ATM and adipocyte sizes were analyzed blindly. Results: The cyclists exercised daily for 10 h and 31 ± 37 min and average intensity was 53 ± 1% of VO2peak. Body weight remained unchanged and VO2peak decreased by 6 ± 2% (P = 0.04). Plasma inflammatory cytokines, TNFα and IL-18 remained unchanged, as did hsCRP, but plasma IL-6 increased significantly. CD163 macrophage content remained unchanged, as did adipocyte cell size. The HbA1c was not significantly decreased, but there was a trend (P < 0.07) toward an increased insulin resistance as estimated by the Quicki Index. Conclusion: The regular prolonged exercise did not influence abdominal adipose tissue inflammation, but the higher plasma IL-6 concentration concurrent with a trend toward higher insulin resistance and decreased VO2peak implies that the excessive amount of exercise probably attenuated the possible potential anti-inflammatory effects of exercise.

Anti-inflammatory effects of active commuting and leisure time exercise in overweight and obese women and men: A randomized controlled trial.

BACKGROUND AND AIMS: Physical inactivity is linked to low-grade inflammation, endothelial dysfunction and cardiovascular disease. We aimed to determine effects of active commuting and leisure time exercise on markers of low-grade inflammation and endothelial function in overweight and obese women and men. METHODS: We randomized 130 younger (20-45 years), physically inactive, healthy, overweight and obese (BMI: 25-35 kg/m2) women and men recruited from the Copenhagen area, Denmark, to either 6 months of habitual lifestyle (CON, n = 18), active commuting (BIKE, n = 35), or leisure time exercise of moderate (MOD, ∼50% VO2peak, n = 39) or vigorous intensity (VIG, ∼70% VO2peak, n = 38). Fasting blood samples were collected at baseline, 3, and 6 months and analyzed for concentrations of C-reactive protein (CRP), fibrinogen, von Willebrand factor (vWF), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1), and 90 participants (CON, n = 16; BIKE, n = 19; MOD, n = 31, VIG, n = 24) were included in a per-protocol analysis. RESULTS: We observed lower concentrations of CRP in MOD compared with CON at 6 months (p = 0.013) and within-group decreases in CRP in BIKE (3 months: p = 0.045) and MOD (3 months: p = 0.061; 6 months: p = 0.038) corresponding to a 30% decrease in BIKE and 19% in MOD from baseline till 6 months. No effects of exercise were observed on fibrinogen, vWF, t-PA, PAI-1 or the t-PA/PAI-1 ratio within or between groups. CONCLUSIONS: Our findings suggest an anti-inflammatory effect of active commuting and moderate, but not vigorous, intensity leisure time exercise, but no alterations in endothelial function during 6 months of intervention.

Repeated Prolonged Exercise Decreases Maximal Fat Oxidation in Older Men.

INTRODUCTION/PURPOSE: Fat metabolism and muscle adaptation was investigated in six older trained men (age, 61 ± 4 yr; V˙O2max, 48 ± 2 mL·kg·min) after repeated prolonged exercise). METHODS: A distance of 2706 km (1681 miles) cycling was performed over 14 d, and a blood sample and a muscle biopsy were obtained at rest after an overnight fast before and 30 h after the completion of the cycling. V˙O2max and maximal fat oxidation were measured using incremental exercise tests. HR was continuously sampled during cycling to estimate exercise intensity. RESULTS: The daily duration of exercise was 10 h and 31 ± 37 min, and the mean intensity was 53% ± 1% of V˙O2max. Body weight remained unchanged. V˙O2max and maximal fat oxidation rate decreased by 6% ± 2% (P = 0.04) and 32% ± 8% (P < 0.01), respectively. The exercise intensity that elicits maximal fat oxidation was not significantly decreased. Plasma free fatty acid (FA) concentration decreased (P < 0.002) from 500 ± 77 µmol·L to 160 ± 38 µmol·L. Plasma glucose concentration as well as muscle glycogen, myoglobin, and triacylglycerol content remained unchanged. Muscle citrate synthase and ß-hydroxy-acyl-CoA-dehydrogenase activities were unchanged, but the protein expression of HKII, GLUT4, and adipose triacylglycerol lipase were significantly increased. CONCLUSIONS: Overall, the decreased maximal fat oxidation was probably due to lower exogenous plasma fatty acid availability and the muscle adaptation pattern indicates an increased glucose transport capacity and an increased muscle lipolysis capacity supporting an increased contribution of exogenous glucose and endogenous fat during exercise.

The GO-ACTIWE randomized controlled trial - An interdisciplinary study designed to investigate the health effects of active commuting and leisure time physical activity.

Regular physical activity is efficacious for improving metabolic health in overweight and obese individuals, yet, many adults lead sedentary lives. Most exercise interventions have targeted leisure time, but physical activity also takes place in other domains of everyday life. Active commuting represents a promising alternative to increase physical activity, but it has yet to be established whether active commuting conveys health benefits on par with leisure time physical activity (LTPA). A 6-month randomized controlled trial was designed to investigate the effects of increased physical activity in transport (bicycling) or leisure time domains (moderate or vigorous intensity endurance exercise). We included 188 overweight and class 1 obese sedentary women and men (20-45years) of which 130 were randomized to either sedentary controls (n=18), active commuting (n=35) or moderate (n=39) or vigorous (n=38) intensity LTPA. At baseline and after 3 and 6months, participants underwent a rigorous 3-day biomedical test regimen followed by free-living measurements. In a sub-sample, physical activity level and energy expenditure were monitored by means of personal assistive technology and the doubly labeled water technique. Additionally, the delivery, reception and routinization of the exercise regimens were investigated by ethnological fieldwork. One year after termination of the intervention, participants will be invited for a follow-up visit to investigate sustained health effects and continuous physical activity adherence. By combining biomedical, technological and humanistic approaches, we aim to understand the health benefits of physical activity in different domains of everyday life, as well as how to improve adherence to physical activity.

Inability to match energy intake with energy expenditure at sustained near-maximal rates of energy expenditure in older men during a 14-d cycling expedition.

BACKGROUND: The upper rates of energy expenditure (EE) and the corresponding regulation of energy intake (EI), as described in younger trained subjects, are not well elucidated in older subjects. OBJECTIVES: The aim was to investigate EE in older men during prolonged cycling and determine whether it is sufficiently matched by EI to maintain energy balance. In addition, we investigated appetite ratings and concentrations of appetite-regulating hormones. DESIGN: Six men (mean ± SE age: 61 ± 3 y) completed 2706 km of cycling, from Copenhagen to Nordkapp, in 14 d. EE was measured by using doubly labeled water, and food and drink intake was recorded by the accompanying scientific staff. Energy balance was calculated as the discrepancy between EI and EE and from changes in body energy stores as derived from deuterium dilution. Fasting hormones were measured before and after cycling, and appetite ratings were recorded twice daily. RESULTS: EE (±SE) increased from 17 ± 1 MJ/d before to 30 ± 2 MJ/d during the cycling trip (P < 0.001), which is equivalent to 4.0 ± 0.1 times the basal metabolic rate. Although body weight remained stable during the 14 d of cycling, body fat decreased (-2.2 ± 0.7 kg; P = 0.02) and fat-free mass increased (2.5 ± 0.6 kg; P = 0.01). EI was 25 ± 1 MJ/d during cycling, resulting in a negative energy balance calculated by the EE - EI gap (-5.2 ± 1.2 MJ/d). Calculated from changes in body energy stores, energy balance was also negative (-4.8 ± 2.0 MJ/d) during the first week. In the morning and evening, hunger ratings increased (both P = 0.02), whereas ratings of fullness decreased in the evening (P = 0.04). Fasting plasma concentrations of insulin increased by 120% ± 15% (P = 0.02), glucagon-like peptide 1 (GLP-1) by 60% ± 20% (P < 0.01), and Polypeptide YY(3-36) by 80% ± 30% (P < 0.02) after cycling. CONCLUSIONS: Older male cyclists sustained near-maximal rates of EE during prolonged cycling but were unable to upregulate EI to maintain energy balance. Despite the presence of increased motivation to eat, a more profound counteracting physiologic stimulus inhibiting increases in EI was present. This trial was registered at clinicaltrials.gov as NCT02353624.

Independent effects of endurance training and weight loss on peak fat oxidation in moderately overweight men: a randomized controlled trial.

Endurance training increases peak fat oxidation (PFO) during exercise, but whether this is independent of changes in body weight is not known. The aim of the present study was to investigate the effects of endurance training with or without weight loss or a diet-induced weight loss on PFO and on key skeletal muscle mitochondrial proteins involved in fat oxidation. Sixty moderately overweight, sedentary but otherwise healthy men were randomized to 12 wk of training (T), diet (D), training and increased caloric intake (T-iD), or continuous sedentary control (C). Isoenergetic deficits corresponding to 600 kcal/day were comprised of endurance exercise for T and caloric restriction for D. T-iD completed similar training but was not in 600 kcal deficit because of dietary replacement. PFO and the exercise intensity at which this occurred (FatMax) were measured by a submaximal exercise test and calculated by polynomial regression. As intended by study design, a similar weight loss was observed in T (-5.9 ± 0.7 kg) and D (-5.2 ± 0.8 kg), whereas T-iD (-1.0 ± 0.5 kg) and C (0.1 ± 0.6 kg) remained weight stable. PFO increased to a similar extent with 42% in T [0.16 g/min; 95% confidence intervals (CI): 0.02; 0.30, P = 0.02] and 41% in T-iD (0.16 g/min; 95% CI: 0.01; 0.30, P = 0.04) compared with C, but did not increase in D (P = 0.96). In addition, the analysis of covariance showed that changes in both PFO (0.10 g/min; 95% CI: 0.03; 0.17, P = 0.03) and FatMax (6.3% V̇o2max; 95% CI: 1.4; 11.3, P < 0.01) were independently explained by endurance training. In conclusion, endurance training per se increases PFO in moderately overweight men.