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Exercise-induced increases in insulin sensitivity after bariatric surgery are mediated by muscle extracellular matrix remodeling

posted on 14.05.2020 by Ada Admin, Wagner S. Dantas, Hamilton Roschel, Igor H. Murai, Saulo Gil, Gangarao Davuluri, Christopher L. Axelrod, Sujoy Ghosh, Susan S. Newman, Hui Zhang, Samuel K. Shinjo, Willian das Neves, Carlos Merege-Filho, Walcy R. Teodoro, Vera L. Capelozzi, Rosa Maria Pereira, Fabiana B. Benatti, Ana L. de Sá-Pinto, Roberto de Cleva, Marco A. Santo, John P. Kirwan, Bruno Gualano
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.


This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (2015/02835-8, 2016/10993-5 and 2017/01427-9). This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. The Genomics Core Facility is supported in part by COBRE (NIH8 1P30GM118430-01) and NORC (NIH 2P30DK072476) center grants from the National Institutes of Health.



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