Exercise-Induced Increases in Insulin Sensitivity After Bariatric Surgery Are Mediated By Muscle Extracellular Matrix Remodeling.

Autor:	Dantas WS; Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA.; Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Roschel H; Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.; Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Murai IH; Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Gil S; Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Davuluri G; Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA., Axelrod CL; Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA.; Department of Translational Services, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA., Ghosh S; Genomics Core, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA.; Cardiovascular and Metabolic Disorders Program and Center for Computational Biology, Duke-National University of Singapore Medical School, Singapore., Newman SS; Genomics Core, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA., Zhang H; Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA., Shinjo SK; Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., das Neves W; Clinical Oncology Service, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil., Merege-Filho C; Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Teodoro WR; Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Capelozzi VL; Department of Pathology, School of Medicine, Universidade de São Paulo, São Paulo, Brazil., Pereira RM; Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Benatti FB; School of Applied Sciences, Universidade Estadual de Campinas, São Paulo, Brazil., de Sá-Pinto AL; Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., de Cleva R; Department of Digestive Division, School of Medicine, Universidade de São Paulo, São Paulo, Brazil., Santo MA; Department of Digestive Division, School of Medicine, Universidade de São Paulo, São Paulo, Brazil., Kirwan JP; Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA., Gualano B; Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil gualano@usp.br.; Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2020 Aug; Vol. 69 (8), pp. 1675-1691. Date of Electronic Publication: 2020 May 14.
DOI:	10.2337/db19-1180
Abstrakt:	Exercise seems to enhance the beneficial effect of bariatric (Roux-en-Y gastric bypass [RYGB]) surgery on insulin resistance. We hypothesized that skeletal muscle extracellular matrix (ECM) remodeling may underlie these benefits. Women were randomized to either a combined aerobic and resistance exercise training program following RYGB (RYGB + ET) or standard of care (RYGB). Insulin sensitivity was assessed by oral glucose tolerance test. Muscle biopsy specimens 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-β1/SMAD 2/3 pathway and its antagonist follistatin. Exercise-induced increases in insulin sensitivity after bariatric surgery are at least partially mediated by muscle ECM remodeling. (© 2020 by the American Diabetes Association.)
Databáze:	MEDLINE
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