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.

Constraints of Weight Loss as a Marker of Bariatric Surgery Success: An Exploratory Study.

PURPOSE: The aim of this exploratory study was to investigate whether the degree of weight loss properly reflects improvements in cardiometabolic health among patients who underwent Roux-en-Y gastric bypass. METHODS: In this ancillary analysis from a clinical trial, patients were clustered into tertiles according to the magnitude of the percentage weight loss (1st tertile: "higher weight loss": -37.1 ± 5.8%; 2nd tertile: "moderate weight loss": -29.7 ± 1.4%; 3rd tertile: "lower weight loss": -24.2 ± 2.3%). Delta changes (9 months after surgery-baseline) in clustered cardiometabolic risk (i.e., blood pressure index, fasting glucose, high-density lipoprotein [HDL] and triglycerides [TG]), glycated hemoglobin (HbA1c), homeostasis model assessment (HOMA-IR), and C-reactive protein (CRP) were calculated. RESULTS: A total of 42 patients who had complete bodyweight data (age = 40 ± 8 year; BMI = 47.8 ± 7.1 kg/m2) were included. Surgery led to substantial weight loss (-37.9 ± 11.3 kg, P < 0,001), and clinically significant improvements in blood pressure index (-17.7 ± 8.2 mmHg, P < 0.001), fasting glucose (-36.6 ± 52.5 mg/dL, P < 0.001), HDL (9.4 ± 7.1 mg/dL, P < 0.001), TG (-35.8 ± 44.1 mg/dL P < 0,001), HbA1c (-1.2 ± 1.6%, P < 0.001), HOMA-IR (-4.7 ± 3.9 mg/dL, P < 0.001) and CRP (-8.5 ± 6.7 µg/mL P < 0.001). Comparisons across tertiles revealed no differences for cardiometabolic risk score, fasting glucose, HbAc1, HOMA-IR, blood pressure index, CRP, HDL, and TG (P > 0.05 for all). Individual variable analysis confirmed cardiometabolic improvements across the spectrum on weight-loss. There were no associations between weight loss and any dependent variable. CONCLUSION: Weight loss following bariatric surgery does not correlate with improvements in cardiovascular risk factors. These findings suggest that weight loss alone may be insufficient to assess the cardiometabolic success of bariatric surgery, and the search for alternate proxies that better predict surgery success are needed.

Exercise Is Key to Sustaining Metabolic Gains After Bariatric Surgery.

The extent to which the benefits of bariatric surgery may be maintained by lifestyle changes after surgery is unclear. Our hypothesis is that exercise may sustain some metabolic benefits and counteract some of the adverse effects of surgery. In this review, we present findings supporting the proposition that exercise is key to improving overall health in patients after bariatric surgery.

Exercise Enhances the Effect of Bariatric Surgery in Markers of Cardiac Autonomic Function.

BACKGROUND: Bariatric surgery improves cardiovascular health, which might be partly ascribed to beneficial alterations in the autonomic nervous system. However, it is currently unknown whether benefits from surgery on cardiac autonomic regulation in post-bariatric patients can be further improved by adjuvant therapies, namely exercise. We investigated the effects of a 6-month exercise training program on cardiac autonomic responses in women undergoing bariatric surgery. METHODS: Sixty-two women eligible for bariatric surgery were randomly allocated to either standard of care (control) or an exercise training intervention. At baseline (PRE) and 3 (POST3) and 9 (POST9) months after surgery, we assessed chronotropic response to exercise (CR%; i.e., percentage change in heart rate from rest to peak exercise) and heart rate recovery (HRR30s, HRR60s, and HRR120s; i.e., decay of heart rate at 30, 60, and 120 s post exercise) after a maximal exercise test. RESULTS: Between-group absolute changes revealed higher CR% (Δ = 8.56%, CI95% 0.22-19.90, P = 0.04), HRR30s (Δ = 12.98 beat/min, CI95% 4.29-21.67, P = 0.01), HRR60s (Δ = 22.95 beat/min, CI95% 11.72-34.18, P = 0.01), and HRR120s (Δ = 34.54 beat/min, CI95% 19.91-49.17, P < 0.01) in the exercised vs. non-exercised group. CONCLUSIONS: Our findings demonstrate that exercise training enhanced the benefits of bariatric surgery on cardiac autonomic regulation. These results highlight the relevance of exercise training as a treatment for post-bariatric patients, ensuring optimal cardiovascular outcomes.

A randomized controlled trial to reduce sedentary time in rheumatoid arthritis: protocol and rationale of the Take a STAND for Health study.

BACKGROUND: Patients with rheumatoid arthritis spend most of their daily hours in sedentary behavior (sitting), a predisposing factor to poor health-related outcomes and all-cause mortality. Interventions focused on reducing sedentary time could be of novel therapeutic relevance. However, studies addressing this topic remain scarce. We aim to investigate the feasibility and efficacy of a newly developed intervention focused on reducing sedentary time, and potential clinical, physiological, metabolic and molecular effects in rheumatoid arthritis. METHODS: The Take a STAND for Health study is a 4-month, parallel-group, randomized controlled trial, in which postmenopausal patients with rheumatoid arthritis will set individually tailored, progressive goals to replace their sedentary time with standing and light-intensity activities. Patients will be recruited from the Clinical Hospital (School of Medicine, University of Sao Paulo) and will be assessed at baseline and after a 4-month follow up. Outcomes will include objectively measured sedentary behavior (primary outcome) and physical activity levels, clinical parameters, anthropometric parameters and body composition; aerobic fitness, muscle function, blood pressure, cardiovascular autonomic function, vascular function and structure, health-related quality of life, and food intake. Blood and muscle samples will be collected for assessing potential mechanisms, through targeted and non-targeted approaches. DISCUSSION: Findings will be of scientific and clinical relevance with the potential to inform new prescriptions focused on reducing sedentary behavior, a modifiable risk factor that thus far has been overlooked in patients with rheumatoid arthritis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03186924. Registered on 14 June 2017.

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.