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

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-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.

Effect of exercise training before and after bariatric surgery: A systematic review and meta‐analysis

“…A more recent study reported similar findings with combined aerobic and resistance training. 65 In both studies, weight and fat loss were similar in the exercise and the nonexercise control group, suggesting an effect of exercise on insulin sensitivity independent of weight loss. Surprisingly, we found no additional benefit of exercise on health-related quality of life after bariatric surgery.…”

Probabilistic outlier identification for RNA sequencing generalized linear models

“…The application of our model to a series of datasets gathered from public sources, including GSE137631 ( 27 ), GSE141027 ( 28 ), GSE99374 ( 29 ), GSE151005 ( 30 ), Mangiola_2018 ( 26 ) and Atkins_2019 ( 31 ), revealed that a median of 10.6%, 3.3% and 10.4% of differentially abundant transcripts inferred by edgeR, the robust edgeR implementation (using estimateGLMRobustDisp) and DESeq2 respectively (using recommended analysis pipelines for data filtering, normalisation and modelling ( 32 , 33 )) had inflated statistics caused by the presence of outliers (Figure 4A ). The analyses were performed using tidybulk framework ( 34 ) and broom ( 35 ).…”

Influence of Adherence to Social Distancing Due to the COVID-19 Pandemic on Physical Activity Level in Post-bariatric Patients

“…In patients who have undergone bariatric surgery, the repercussion of physical inactivity and sedentary behavior during the post-operative period is underexplored; however, higher physical activity has been associated with better cardiometabolic risk factors [6]. Furthermore, exercise training has been shown to improve insulin resistance [7], vascular function [8], and inflammatory markers [8]. Thus, increasing physical activity could be a key strategy to improve overall health among post-bariatric patients and is confined during the pandemic.…”