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

Author(s):Show less -

Dantas, Wagner S. ^{[1, 2]} ; Roschel, Hamilton ^{[1, 3]} ; Murai, Igor H. ^[1] ; Gil, Saulo ^[1] ; Davuluri, Gangarao ^[2] ; Axelrod, Christopher L. ^{[2, 4]} ; Ghosh, Sujoy ^{[5, 6, 7]} ; Newman, Susan S. ^[5] ; Zhang, Hui ^[2] ; Shinjo, Samuel K. ^[3] ; das Neves, Willian ^[8] ; Merege-Filho, Carlos ^[1] ; Teodoro, Walcy R. ^[3] ; Capelozzi, Vera L. ^[9] ; Pereira, Rosa Maria ^[3] ; Benatti, Fabiana B. ^[10] ; de Sa-Pinto, Ana L. ^[3] ; de Cleva, Roberto ^[11] ; Santo, Marco A. ^[11] ; Kirwan, John P. ^[2] ; Gualano, Bruno ^{[1, 3]}

Affiliation:Show less -

^[1] Univ Sao Paulo, Appl Physiol & Nutr Res Grp, Sch Phys Educ & Sport, Lab Assessment & Conditioning Rheumatol, Fac Med, Sao Paulo, SP - Brazil

^[2] Louisiana State Univ, Integrated Physiol & Mol Metab Lab, Pennington Biomed Res Ctr, Baton Rouge, LA 70803 - USA

^[3] Univ Sao Paulo, Fac Med, Hosp Clin, Rheumatol Div, Sao Paulo, SP - Brazil

^[4] Louisiana State Univ, Pennington Biomed Res Ctr, Dept Translat Serv, Baton Rouge, LA 70808 - USA

^[5] Louisiana State Univ, Pennington Biomed Res Ctr, Genom Core, Baton Rouge, LA 70808 - USA

^[6] Duke Natl Univ Singapore Med Sch, Cardiovasc & Metab Disorders Program, Singapore - Singapore

^[7] Duke Natl Univ Singapore Med Sch, Ctr Computat Biol, Singapore - Singapore

^[8] Inst Canc Estado Sao Paulo, Clin Oncol Serv, Sao Paulo, SP - Brazil

^[9] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo, SP - Brazil

^[10] Univ Estadual Campinas, Sch Appl Sci, Sao Paulo, SP - Brazil

^[11] Univ Sao Paulo, Sch Med, Dept Digest Div, Sao Paulo - Brazil

• Document type: Journal article
• Source: Diabetes; v. 69, n. 8, p. 1675-1691, AUG 2020.
• Web of Science Citations: 0

Abstract

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-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 ECM remodeling. (AU)

• FAPESP's process: 15/02835-8 - Effects of exercise training on insulin resistance and lipid oxidation in skeletal muscle in patients undergoing bariatric surgery: a randomized trial
• Grantee: Wagner Silva Dantas
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/10993-5 - Effects of exercise training in patients undergoing bariatric surgery: a randomized and clinical trial
• Grantee: Hamilton Augusto Roschel da Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/01427-9 - Molecular mechanisms involved in the extracellular matrix remodeling of skeletal muscle of obese patients undergoing bariatric surgery: role of insulin resistance and effects of exercise training
• Grantee: Wagner Silva Dantas
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate