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 <i>in vitro</i>. Exercise training improved insulin sensitivity beyond
surgery alone (<i>e.g</i>., Matsuda index - RYGB:
+123% vs. RYGB + ET: +325%; <i>P </i>≤ 0.0001).
ECM remodeling was reduced by surgery alone, with an additive benefit of
surgery and exercise training (<i>e.g.,</i>
collagen I - RYGB: -41% vs. RYGB + ET: -76%; <i>P </i>≤ 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.
Insulin Resistance, Skeletal Muscle Extracellular Matrix Remodeling, And The Effect Of Exercise