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.