RT Journal Article SR Electronic T1 Exercise-Induced Increases in Insulin Sensitivity After Bariatric surgery are Mediated by Muscle Extracellular Matrix Remodeling JF Diabetes JO Diabetes FD American Diabetes Association SP db191180 DO 10.2337/db19-1180 A1 Dantas, Wagner S. A1 Roschel, Hamilton A1 Murai, Igor H. A1 Gil, Saulo A1 Davuluri, Gangarao A1 Axelrod, Christopher L. A1 Ghosh, Sujoy A1 Newman, Susan S. A1 Zhang, Hui A1 Shinjo, Samuel K. A1 Neves, Willian das A1 Merege-Filho, Carlos A1 Teodoro, Walcy R. A1 Capelozzi, Vera L. A1 Pereira, Rosa Maria A1 Benatti, Fabiana B. A1 de Sá-Pinto, Ana L. A1 de Cleva, Roberto A1 Santo, Marco A. A1 Kirwan, John P. A1 Gualano, Bruno YR 2020 UL http://diabetes.diabetesjournals.org/content/early/2020/05/11/db19-1180.abstract AB Exercise seems to enhance the beneficial effect of bariatric surgery (RYGB) on insulin resistance. We hypothesized that skeletal muscle extracellular matrix (ECM) remodeling may underly these benefits. Women were randomized to either a combined aerobic and resistance exercise training program following RYGB or standard of care (RYGB). Insulin sensitivity was assessed by OGTT. Muscle biopsies 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-beta 1/SMAD 2/3 pathway and its antagonist follistatin. Exercise-induced increases in insulin sensitivity after bariatric surgery are at least partially mediated by muscle extracellular matrix remodeling. Clinicaltrial.gov: NCT02441361.