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.

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.

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.

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.

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.

Three months of strictly controlled daily endurance exercise reduces thrombin generation and fibrinolytic risk markers in younger moderately overweight men.

PURPOSE: Physical activity is associated with a decreased risk of cardiovascular disease, but dose dependency of long-term physical exercise on biomarkers within coagulation and fibrinolysis is unknown. We aimed to investigate effects of two doses of daily endurance exercise on biomarkers of the haemostatic balance in overweight men. METHODS: Haemostatic variables were investigated in 53 healthy, younger (20-40 years), moderately overweight (BMI 25-30 kg/m(2)) men randomly assigned to 3 months of strictly controlled endurance exercise at two different doses corresponding to an energy expenditure of 600 kcal/day (HIGH), 300 kcal/day (MOD), or to maintain their habitual lifestyle (CON). Fasting blood samples were collected before and after the intervention and analysed for thrombin generation (endogenous thrombin potential, ETP) and concentrations of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and von Willebrand factor (vWF). RESULTS: We observed significant within-group decreases in ETP (MOD 7 %; HIGH 6 %) and in t-PA (MOD 22 %; HIGH 21 %) and PAI-1 (MOD 16 %; HIGH 32 %) in both training groups, and no changes in the CON group. At 3 months, between-group differences were observed for ETP (p = 0.016) and t-PA (p = 0.012) due to significantly lower values in MOD and HIGH compared with CON. Borderline significant between-group differences were observed for PAI-1 (p = 0.082). A significant increase was observed in vWF in HIGH, but with no between-group differences. CONCLUSIONS: Our results demonstrate an effect of 3 months of daily endurance exercise on biomarkers of the haemostatic balance in the direction of reduced cardiovascular risk, independent of exercise dose.

Compliance with physical exercise: using a multidisciplinary approach within a dose-dependent exercise study of moderately overweight men.

AIMS: Sixty-one healthy, sedentary, moderately overweight young men participated in a randomised controlled trial to examine the effects of two different doses of endurance exercise on health behaviour and exercise compliance. METHODS: Participants were randomised to a sedentary control group, a moderate (MOD; 300 kcal/day) or a high-dose (HIGH; 600 kcal/day) endurance exercise group for 12 weeks. A sub-set of the subjects were interviewed using pre-determined, qualitative questions to elucidate physical activity and health behaviour. In combination with the Theory of Planned Behaviour (TPB), a post hoc thematic analysis was conducted to connect qualitative and quantitative data in a joint analysis. RESULTS: Of the subjects interviewed, exercise compliance expressed as 95% CI was [96.8; 103%] in the MOD group and [82.9; 99.6%] in the HIGH group. The different doses of daily exercise equally improved various metabolic health parameters. The MOD group was untroubled by the exercise load and had a positive attitude towards exercise. The HIGH group expressed increased fatigue, less positivity and perceived exercise as time-consuming. The MOD group described themselves as more energetic, and thereby may have increased physical activity levels in areas of their everyday lives that were not related to the intervention. CONCLUSIONS: A multidisciplinary approach provided explanations for similar effects of two different doses of exercise. This could not have been determined via either qualitative or quantitative methodology alone. The preconditions of the TBP were fulfilled, and it represents a methodological model to explain the high degree of compliance and motivation to exercise.

Appetite regulation in overweight, sedentary men after different amounts of endurance exercise: a randomized controlled trial.

Weight loss induced by endurance exercise is often disappointing, possibly due to an increase in energy intake mediated through greater appetite. The aim of this study was to evaluate fasting, postprandial, and postexercise appetite regulation after an intervention prescribing two amounts of endurance exercise. Sixty-four sedentary, overweight, healthy young men were randomized to control (CON), moderate-dose (MOD: ≈ 30 min/day), or high-dose (HIGH: ≈ 60 min/day) endurance exercise for 12 wk. Along with subjective appetite ratings, plasma ghrelin, glucagon, insulin, peptide YY3-36, glucose, free fatty acids, and glycerol were measured during fasting and in relation to a breakfast meal and an acute bout of exercise, both at baseline and at follow-up. Ad libitum lunch energy intake was evaluated 3 h after the breakfast meal. Despite different amounts of endurance exercise, the subjects lost similar amounts of fat mass (MOD: 4.2 ± 0.5 kg; HIGH: 3.7 ± 0.5 kg). Fasting and postprandial insulin decreased ≈ 20% in both exercise groups (P < 0.03 vs. CON). Appetite measurements were not upregulated in the fasting and postprandial states. On the contrary, fasting and postprandial ratings of fullness and postprandial PYY3-36 increased in HIGH (P < 0.001 vs. CON). Ad libitum lunch energy intake remained unchanged over the course of the intervention. In both exercise groups, plasma ghrelin increased in relation to acute exercise after training. Thus neither moderate nor high doses of daily endurance exercise increased fasting and postprandial measures of appetite, but a high dose of exercise was associated with an increase in fasting and meal-related ratings of fullness and satiety.