nondiabetic patients following RYGB surgery are typically quite modest compared with the presurgery condition (3). Moreover, there appear to be 2 discrete periods of improvement. The first is immediately after surgery, at which time hepatic, but not peripheral, S I improves in response to acute energy restriction (4-6), while greater, protracted weight loss appears to be more strongly associated with improved peripheral S I (7,8). Even with significant weight loss 1 year following RYBG surgery, peripheral S I is still low compared with that of lean metabolically healthy individuals (3,5,6,9).Exercise is considered a cornerstone for obesity treatment, and while it is not generally viewed to cause substantial body weight reduction (10), it can potently improve peripheral S I and glucose control (11-13) and can reduce the risk of T2D and cardiovascular disease (14,15). There is general consensus that even a single session of moderate intensity exercise can induce an improvement in S I (16). There is also evidence that exercise can BACKGROUND. Roux-en-Y gastric bypass (RYGB) surgery causes profound weight loss and improves insulin sensitivity (S I ) in obese patients. Regular exercise can also improve S I in obese individuals; however, it is unknown whether exercise and RYGB surgery-induced weight loss would additively improve S I and other cardiometabolic factors. METHODS.We conducted a single-blind, prospective, randomized trial with 128 men and women who recently underwent RYGB surgery (within 1-3 months). Participants were randomized to either a 6-month semi-supervised moderate exercise protocol (EX, n = 66) or a health education control (CON; n = 62) intervention. Main outcomes measured included S I and glucose effectiveness (S G ), which were determined from an intravenous glucose tolerance test and minimal modeling. Secondary outcomes measured were cardiorespiratory fitness (VO 2 peak) and body composition. Data were analyzed using an intention-to-treat (ITT) and per-protocol (PP) approach to assess the efficacy of the exercise intervention (>120 min of exercise/week).RESULTS. 119 (93%) participants completed the interventions, 95% for CON and 91% for EX. There was a significant decrease in body weight and fat mass for both groups (P < 0.001 for time effect). S I improved in both groups following the intervention (ITT: CON vs. EX; +1.64 vs. +2.24 min -1 /μU/ml, P = 0.18 for Δ, P < 0.001 for time effect). A PP analysis revealed that exercise produced an additive S I improvement (PP: CON vs. EX; +1.57 vs. +2.69 min

Both Roux-en-Y gastric bypass (RYGB) surgery and exercise can improve insulin sensitivity in individuals with severe obesity. However, the impact of RYGB with or without exercise on skeletal muscle mitochondria, intramyocellular lipids, and insulin sensitivity index (SI) is unknown. We conducted a randomized exercise trial in patients (n = 101) who underwent RYGB surgery and completed either a 6-month moderate exercise (EX) or a health education control (CON) intervention. SI was determined by intravenous glucose tolerance test. Mitochondrial respiration and intramyocellular triglyceride, sphingolipid, and diacylglycerol content were measured in vastus lateralis biopsy specimens. We found that EX provided additional improvements in SI and that only EX improved cardiorespiratory fitness, mitochondrial respiration and enzyme activities, and cardiolipin profile with no change in mitochondrial content. Muscle triglycerides were reduced in type I fibers in CON, and sphingolipids decreased in both groups, with EX showing a further reduction in a number of ceramide species. In conclusion, exercise superimposed on bariatric surgery–induced weight loss enhances mitochondrial respiration, induces cardiolipin remodeling, reduces specific sphingolipids, and provides additional improvements in insulin sensitivity.

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

ObjectiveWe investigated the associations of both physical activity time (PA) and energy expenditure (EE) with weight and fat mass (FM) loss in patients following Roux-en-Y gastric bypass (RYGB) surgery.MethodsNinety-six non-diabetic patients were included in this analysis. Post RYGB patients were randomized in one of two treatments: A 6-month exercise training program (RYBG+EX) or lifestyle educational classes (RYGB). Body composition was assessed by dual-energy X-ray absorptiometry and computed tomography. We quantified components of PA and EE by a multisensory device. We explored dose-response relationships of both PA and EE with weight loss and body composition according to quartiles of change in steps/day.ResultsPatients in the highest quartile of steps/day change lost more fat mass (FM) (3rd =−19.5kg and 4th=−22.7kg, P<0.05) and abdominal adipose tissue (− 4th=−313cm2, P<0.05);, maintained skeletal muscle mass (3rd = 3.1cm2 and −4th=−4.5cm2, P<0.05) and had greater reductions in resting metabolic rate. Decreases in sedentary EE, increases in Light EE and age were significant predictors of both Δweight and ΔFM (R2 =73.8% and R2 =70.6%, respectively).ConclusionNon-diabetic patients who perform higher - yet still modest - amounts of PA following RYGB have greater energy deficits, lose more weight and body fat mass, while maintaining higher skeletal muscle mass.

Objective The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and to determine the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. Approach and Results Young, sedentary men and women were divided into lean (BMI 18–25; n=14), intermediate (BMI 28–32.5; n=13), and obese (BMI 33–40; n=15) groups. A novel microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H2O2) and superoxide levels in the vastus lateralis of obese compared to both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase (Nox) inhibitor, lowered (normalized) H2O2 and superoxide levels and reversed microvascular endothelial dysfunction in obese subjects. Following 8-weeks of exercise, H2O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the Nox subunits p22phox, p47phox, and p67phox were increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuated by exercise training in obese subjects. Conclusions This study implicates Nox as a source of excessive ROS production in skeletal muscle of obese individuals, and links excessive Nox derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these maladies.