Exercise modifies hypothalamic connectivity and brain functional networks in women after bariatric surgery: a randomized clinical trial.

BACKGROUND: Obesity is a disease that may involve disrupted connectivity of brain networks. Bariatric surgery is an effective treatment for obesity, and the positive effects on obesity-related conditions may be enhanced by exercise. Herein, we aimed to investigate the possible synergistic effects of Roux-en-Y Gastric Bypass (RYGB) and exercise training on brain functional networks. METHODS: Thirty women eligible for bariatric surgery were randomly assigned to a Roux-en-Y gastric bypass (RYGB: n = 15, age = 41.0 ± 7.3 years) or RYGB plus Exercise Training (RYGB + ET: n = 15, age = 41.9 ± 7.2 years). Clinical, laboratory, and brain functional connectivity parameters were assessed at baseline, and 3 (POST3) and 9 months (POST9) after surgery. The 6-month, three-times-a-week, exercise intervention (resistance plus aerobic exercise) was initiated 3 months post-surgery (for RYGB + ET). RESULTS: Exercise superimposed on bariatric surgery (RYGB + ET) increased connectivity between hypothalamus and sensorial regions (seed-to-voxel analyses of hypothalamic connectivity), and decreased default mode network (DMN) and posterior salience (pSAL) network connectivity (ROI-to-ROI analyses of brain networks connectivity) when compared to RYGB alone (all p-FDR < 0.05). Increases in basal ganglia (BG) network connectivity were only observed in the exercised training group (within-group analyses). CONCLUSION: Exercise training is an important component in the management of post-bariatric patients and may improve the hypothalamic connectivity and brain functional networks that are involved in controlling food intake. TRIAL REGISTRATION: Clinicaltrial.gov: NCT02441361.

A randomized clinical trial on the effects of exercise on muscle remodelling following bariatric surgery.

BACKGROUND: Muscle atrophy and strength loss are common adverse outcomes following bariatric surgery. This randomized, controlled trial investigated the effects of exercise training on bariatric surgery-induced loss of muscle mass and function. Additionally, we investigated the effects of the intervention on molecular and histological mediators of muscle remodelling. METHODS: Eighty women with obesity were randomly assigned to a Roux-en-Y gastric bypass (RYGB: n = 40, age = 42 ± 8 years) or RYGB plus exercise training group (RYGB + ET: n = 40, age = 38 ± 7 years). Clinical and laboratory parameters were assessed at baseline, and 3 (POST3) and 9 months (POST9) after surgery. The 6 month, three-times-a-week, exercise intervention (resistance plus aerobic exercise) was initiated 3 months post-surgery (for RYGB + ET). A healthy, lean, age-matched control group was recruited to provide reference values for selected variables. RESULTS: Surgery resulted in a similar (P = 0.66) reduction in lower-limb muscle strength in RYGB and RYGB+ET (-26% vs. -31%), which was rescued to baseline values in RYGB + ET (P = 0.21 vs. baseline) but not in RYGB (P < 0.01 vs. baseline). Patients in RYGB+ET had greater absolute (214 vs. 120 kg, P < 0.01) and relative (2.4 vs. 1.4 kg/body mass, P < 0.01) muscle strength compared with RYGB alone at POST9. Exercise resulted in better performance in timed-up-and-go (6.3 vs. 7.1 s, P = 0.05) and timed-stand-test (18 vs. 14 repetitions, P < 0.01) compared with RYGB. Fat-free mass was lower (POST9-PRE) after RYBG than RYGB + ET (total: -7.9 vs. -4.9 kg, P < 0.01; lower-limb: -3.8 vs. -2.7 kg, P = 0.02). Surgery reduced Types I (~ - 21%; P = 0.99 between-group comparison) and II fibre cross-sectional areas (~ - 27%; P = 0.88 between-group comparison), which were rescued to baseline values in RYGB+ET (P > 0.05 vs. baseline) but not RYGB (P > 0.01 vs. baseline). RYGB + ET showed greater Type I (5187 vs. 3898 µm2 , P < 0.01) and Type II (5165 vs. 3565 µm2 , P < 0.01) fCSA than RYGB at POST9. RYGB + ET also resulted in increased capillarization (P < 0.01) and satellite cell content (P < 0.01) than RYGB at POST9. Gene-set normalized enrichment scores for the muscle transcriptome revealed that the ubiquitin-mediated proteolysis pathway was suppressed in RYGB + ET at POST9 vs. PRE (NES: -1.7; P < 0.01), but not in RYGB. Atrogin-1 gene expression was lower in RYGB + ET vs. RYGB at POST9 (0.18 vs. 0.71-fold change, P < 0.01). From both genotypic and phenotypic perspectives, the muscle of exercised patients resembled that of healthy lean individuals. CONCLUSIONS: This study provides compelling evidence-from gene to function-that strongly supports the incorporation of exercise into the recovery algorithm for bariatric patients so as to counteract the post-surgical loss of muscle mass and function.

Exercise-Induced Increases in Insulin Sensitivity After Bariatric Surgery Are Mediated By Muscle Extracellular Matrix Remodeling.

Exercise seems to enhance the beneficial effect of bariatric (Roux-en-Y gastric bypass [RYGB]) surgery on insulin resistance. We hypothesized that skeletal muscle extracellular matrix (ECM) remodeling may underlie these benefits. Women were randomized to either a combined aerobic and resistance exercise training program following RYGB (RYGB + ET) or standard of care (RYGB). Insulin sensitivity was assessed by oral glucose tolerance test. Muscle biopsy specimens were obtained at baseline and 3 and 9 months after surgery and subjected to comprehensive phenotyping, transcriptome profiling, molecular pathway identification, and validation in vitro. Exercise training improved insulin sensitivity beyond surgery alone (e.g., Matsuda index: RYGB 123% vs. RYGB + ET 325%; P ≤ 0.0001). ECM remodeling was reduced by surgery alone, with an additive benefit of surgery and exercise training (e.g., collagen I: RYGB -41% vs. RYGB + ET -76%; P ≤ 0.0001). Exercise and RYGB had an additive effect on enhancing insulin sensitivity, but surgery alone did not resolve insulin resistance and ECM remodeling. We identified candidates modulated by exercise training that may become therapeutic targets for treating insulin resistance, in particular, the transforming growth factor-ß1/SMAD 2/3 pathway and its antagonist follistatin. Exercise-induced increases in insulin sensitivity after bariatric surgery are at least partially mediated by muscle ECM remodeling.

Low-Load Resistance Training With Blood-Flow Restriction in Relation to Muscle Function, Mass, and Functionality in Women With Rheumatoid Arthritis.

OBJECTIVE: To evaluate the effects of a low-load resistance training program associated with partial blood-flow restriction in patients with rheumatoid arthritis (RA). METHODS: Forty-eight women with RA were randomized into 1 of 3 groups: high-load resistance training (HL-RT; 70% 1 repetition maximum [1RM]), low-load resistance training (30% 1RM) with partial blood-flow restriction training (BFRT), and a control group. Patients completed a 12-week supervised training program and were assessed for lower-extremity 1RM, quadriceps cross-sectional area (CSA), physical function (timed-stands test [TST], timed-up-and-go test [TUG], and Health Assessment Questionnaire [HAQ]), and quality of life (Short Form 36 health survey [SF-36]) at baseline and after the intervention. RESULTS: BFRT and HL-RT were similarly effective in increasing maximum dynamic strength in both leg press (22.8% and 24.2%, respectively; P < 0.0001 for all) and knee extension (19.7% and 23.8%, respectively; P < 0.0001 for all). Quadriceps CSA was also significantly increased in both BFRT and HL-RT (9.5% and 10.8%, respectively; P < 0.0001 for all). Comparable improvements in TST (11.2% and 14.7%; P < 0.0001 for all) and TUG (-6.8% [P < 0.0053] and -8.7% [P < 0.0001]) were also observed in BFRT and HL-RT, respectively. Improvements in both groups were significantly greater than those of the control group (P < 0.05 for all). SF-36 role physical and bodily pain and HAQ scores were improved only in BFRT (45.7%, 22.5%, and -55.9%, respectively; P < 0.05 for all). HL-RT resulted in 1 case of withdrawal and several cases of exercise-induced pain, which did not occur in BFRT. CONCLUSION: BFRT was effective in improving muscle strength, mass, function, and health-related quality of life in patients with RA, emerging as a viable therapeutic modality in RA management.

Exercise Mitigates Bone Loss in Women With Severe Obesity After Roux-en-Y Gastric Bypass: A Randomized Controlled Trial.

CONTEXT: Bone loss after bariatric surgery potentially could be mitigated by exercise. OBJECTIVE: To investigate the role of exercise training (ET) in attenuating bariatric surgery-induced bone loss. DESIGN: Randomized, controlled trial. SETTING: Referral center for bariatric surgery. PATIENTS: Seventy women with severe obesity, aged 25 to 55 years, who underwent Roux-en-Y gastric bypass (RYGB). INTERVENTION: Supervised, 6-month, ET program after RYGB vs. standard of care (RYGB only). OUTCOMES: Areal bone mineral density (aBMD) was the primary outcome. Bone microarchitecture, bone turnover, and biochemical markers were secondary outcomes. RESULTS: Surgery significantly decreased femoral neck, total hip, distal radius, and whole body aBMD (P < 0.001); and increased bone turnover markers, including collagen type I C-telopeptide (CTX), procollagen type I N-propeptide (P1NP), sclerostin, and osteopontin (P < 0.05). Compared with RYGB only, exercise mitigated the percent loss of aBMD at femoral neck [estimated mean difference (EMD), -2.91%; P = 0.007;], total hip (EMD, -2.26%; P = 0.009), distal radius (EMD, -1.87%; P = 0.038), and cortical volumetric bone mineral density at distal radius (EMD, -2.09%; P = 0.024). Exercise also attenuated CTX (EMD, -0.20 ng/mL; P = 0.002), P1NP (EMD, -17.59 ng/mL; P = 0.024), and sclerostin levels (EMD, -610 pg/mL; P = 0.046) in comparison with RYGB. Exercise did not affect biochemical markers (e.g., 25(OH)D, calcium, intact PTH, phosphorus, and magnesium). CONCLUSION: Exercise mitigated bariatric surgery-induced bone loss, possibly through mechanisms involving suppression in bone turnover and sclerostin. Exercise should be incorporated in postsurgery care to preserve bone mass.

Prescribed Versus Preferred Intensity Resistance Exercise in Fibromyalgia Pain.

Exercise is the treatment of choice for fibromyalgia (FM), but little is known about resistance exercise prescription to modulate pain in this condition. This study aimed to compare the effects of different resistance exercise models, comprising self-selected or prescribed intensity, on pain in FM patients. In a cross-over fashion, 32 patients underwent the following sessions: (i) standard prescription (STD; 3 × 10 repetitions at 60% of maximal strength); (ii) self-selected load with fixed number of repetitions (SS); (iii) self-selected load with volume load (i.e., load × sets × repetitions) matched for STD (SS-VM); and (iv) self-selected load with a free number of repetitions until achieving score 7 of rating perceived exertion (SS-RPE). Pain, assessed by Visual Analogic Scale (VAS) and Short-Form McGill Pain Questionnaire (SF-MPQ), was evaluated before and 0, 24, 48, 72, and 96 h after the sessions. Load was significantly lower in SS, SS-VM, SS-RPE than in STD, whereas rating perceived exertion and volume load were comparable between sessions. VAS scores increased immediately after all sessions (p < 0.0001), and reduced after 48, 72, 96 h (p < 0.0001), remaining elevated compared to pre-values. SF-MPQ scores increased immediately after all exercise sessions (p = 0.025), then gradually reduced across time, reaching baseline levels at 24 h. No significant differences between sessions were observed. Both prescribed and preferred intensity resistance exercises failed in reducing pain in FM patients. The recommendation that FM patients should exercise at preferred intensities to avoid exacerbated pain, which appears to be valid for aerobic exercise, does not apply to resistance exercise.

Exercise in Takayasu Arteritis: Effects on Inflammatory and Angiogenic Factors and Disease-Related Symptoms.

OBJECTIVE: To investigate the effects of acute and chronic exercise in female patients with remissive Takayasu arteritis (TAK). METHODS: This was a 2-part prospective study. In study 1, cytokines and soluble tumor necrosis factor (TNF) receptors were assessed at rest and every 60 minutes during a 3-hour recovery period following an acute exercise session in TAK (n = 11) and heathy control (n = 10) groups. In study 2, a subsample from the TAK group (n = 6) underwent a 12-week exercise training program. Before and after training, the acute session of aerobic exercise was performed and cytokines and soluble TNF receptors were assessed at the same time points described above. Muscle function, strength, aerobic capacity, endothelial function, quality of life, and walking impairment scores were evaluated. RESULTS: In study 1, the acute session of aerobic exercise led to overall similar responses on cytokine kinetics in the TAK and heathy control groups. In study 2, the exercise training program did not exacerbate inflammatory cytokines in TAK patients, while the proinflammatory cytokine TNF was diminished both at rest and following the acute session of aerobic exercise. In addition, the exercise training program increased the pro-angiogenic factors vascular endothelial growth factor (at rest) and platelet-derived growth factor AA (at rest and in response to the acute session of aerobic exercise). The exercise training program improved muscle strength and function, whereas aerobic capacity, quality of life, and endothelial function parameters remained unchanged. CONCLUSION: Exercise could be a well-tolerated, safe, and effective intervention able to induce immunomodulatory and pro-angiogenic effects and to increase strength and function in patients with TAK.

Randomized clinical trial: benefits of aerobic physical activity for 24 weeks in postmenopausal women with nonalcoholic fatty liver disease.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of aerobic physical activity in reducing the frequency of hepatic steatosis and metabolic and cardiovascular risk in postmenopausal women with nonalcoholic fatty liver disease (NAFLD). METHODS: Forty sedentary postmenopausal women (mean age 55.3 ±â€Š8.0 y) with biopsy-proven NAFLD were randomly divided into two groups: an exercising group (19 participants) and a control group (nonexercising, 21 participants). The exercise group underwent a supervised aerobic physical activity program of 120 min/wk for 24 weeks. The anthropometric parameters; body composition; hepatic, lipid, and glycemic profiles; homeostasis model assessment of insulin resistance index; cytokines; transient elastography (FibroScan; liver stiffness/controlled attenuation parameter); and cardiopulmonary exercise test were evaluated at baseline and after 24 weeks of protocol. RESULTS: At baseline there were no significant differences in anthropometric, metabolic, and inflammatory parameters-stiffness and liver fat content by FibroScan between the groups. After 24 weeks, we observed a decrease of waist circumference, an increase of high-density lipoprotein cholesterol levels (P < 0.05), and improved cardiopulmonary functional capacity in the exercise group. In addition, the controlled attenuation parameter analysis showed no significant decrease of hepatic steatosis in the exercise group. With regard to the systemic inflammation, there were, however, no significant differences in the cytokines between the groups. CONCLUSIONS: An aerobic physical activity program of 24 weeks in NAFLD postmenopausal women showed improvement in some variables such as waist circumference, high-density lipoprotein cholesterol, and cardiopulmonary performance that may be beneficial in improving cardiovascular risk factors in this population.

Reduced Aerobic Capacity and Quality of Life in Physically Inactive Patients With Systemic Lupus Erythematosus With Mild or Inactive Disease.

OBJECTIVE: To compare aerobic capacity and health-related quality of life (HRQOL) in physically inactive adult systemic lupus erythematosus (A-SLE) and childhood-onset systemic lupus erythematosus (C-SLE) patients with mild/inactive disease versus healthy controls. METHODS: In a cross-sectional study, 39 patients (C-SLE: n = 18, ages 9-18 years; and A-SLE: n = 21, ages 23-45 years) with inactive disease activity (Systemic Lupus Erythematosus Disease Activity Index ≤4) and low cumulative damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index ≤2) and 30 healthy controls (15 children and adolescents [C-CTRL], 15 adults [A-CTRL]) matched by physical inactivity, age, sex, and body mass index (BMI) were assessed for aerobic capacity and HRQOL. RESULTS: All participants were considered physically inactive according to physical activity guidelines. C-SLE and A-SLE patients showed lower VO2peak (95% CI confidence interval [95% CI] -10.5, -1.2 and -11.1, -3.8, respectively) and higher time-to-exhaustion when compared with C-CTRL and A-CTRL (95% CI -2.8, 0.1 and -3.9, -1.7, respectively). C-SLE patients showed significantly lower scores in scholar functioning from the Pediatric Quality of Life Inventory questionnaire (P < 0.05) whereas A-SLE patients showed lower scores in most domains of the Short Form 36 health survey questionnaire (physical function, role-physical, bodily pain, general health, vitality, social function, and mental health) when compared with healthy controls (P < 0.05 for all). CONCLUSION: Our study provides novel data suggesting that A-SLE and C-SLE patients with mild/inactive disease have impaired aerobic capacity and HRQOL when compared with controls matched by physical inactivity, age, sex, and BMI. These findings reinforce the recommendation of physical activity in SLE treatment.

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial.

INTRODUCTION: Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients. METHODS: Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO2, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise). RESULTS: The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO2 (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study. CONCLUSION: A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients. TRIAL REGISTRATION: NCT01515163.

Beta-alanine (Carnosyn™) supplementation in elderly subjects (60-80 years): effects on muscle carnosine content and physical capacity.

The aim of this study was to investigate the effects of beta-alanine supplementation on exercise capacity and the muscle carnosine content in elderly subjects. Eighteen healthy elderly subjects (60-80 years, 10 female and 4 male) were randomly assigned to receive either beta-alanine (BA, n=12) or placebo (PL, n=6) for 12 weeks. The BA group received 3.2 g of beta-alanine per day (2×800 mg sustained-release Carnosyn™ tablets, given 2 times per day). The PL group received 2× (2×800 mg) of a matched placebo. At baseline (PRE) and after 12 weeks (POST-12) of supplementation, assessments were made of the muscle carnosine content, anaerobic exercise capacity, muscle function, quality of life, physical activity and food intake. A significant increase in the muscle carnosine content of the gastrocnemius muscle was shown in the BA group (+85.4%) when compared with the PL group (+7.2%) (p=0.004; ES: 1.21). The time-to-exhaustion in the constant-load submaximal test (i.e., TLIM) was significantly improved (p=0.05; ES: 1.71) in the BA group (+36.5%) versus the PL group (+8.6%). Similarly, time-to-exhaustion in the incremental test was also significantly increased (p=0.04; ES 1.03) following beta-alanine supplementation (+12.2%) when compared with placebo (+0.1%). Significant positive correlations were also shown between the relative change in the muscle carnosine content and the relative change in the time-to-exhaustion in the TLIM test (r=0.62; p=0.01) and in the incremental test (r=0.48; p=0.02). In summary, the current data indicate for the first time, that beta-alanine supplementation is effective in increasing the muscle carnosine content in healthy elderly subjects, with subsequent improvement in their exercise capacity.

Musculoskeletal findings in obese children.

AIM: A cross-sectional study was conducted to explore osteoarticular alterations in obese children. METHODS: Twenty-five boys and 24 girls (mean age: 10.8+/-2.07 years) with a body mass index (BMI) above the 95th percentile were compared with 28 boys and 19 girls (controls, mean age: 10.4+/-2.3 years) with a BMI below the 80th percentile. RESULTS: A higher frequency of at least one osteoarticular manifestation was observed in obese patients (55%) compared with the control group (23%) (P=0.001). A statistically significant association was also found between obesity and lower back pain, genu valgum, genu recurvatum and tight quadriceps. Fibromyalgia tender points (=11) were present at similar frequency in both groups (obese: 3/38 (9%) vs. control: 1/48 (2%)). CONCLUSION: The present data suggest that obesity has a negative impact on osteoarticular health by promoting biomechanical changes in the lumbar spine and lower extremities.