Abstract
Muscle wasting observed in obese women undergoing bariatric surgery is likely related to altered abnormal intramyocellular signaling. Exercise may reestablish the anabolic capacity in this condition. PURPOSE: We examined the effects of exercise training on the main pathways related to skeletal muscle plasticity in obese women undergoing bariatric surgery. METHODS: Women with severe obesity were randomly allocated to either bariatric surgery (RYGB) or bariatric surgery followed by exercise (RYGB+ET). A 6-month, three-times-a-week, supervised, combined aerobic and resistance training program started 3 months after surgery for RYGB+ET, while RYGB followed standard of care. We assessed the transcriptome (RNA-seq) from skeletal muscle samples obtained by muscle biopsies (n = 6 per group) at baseline (PRE) and 9 months after surgery (POST9). We tested whether a set of genes defined a priori were differentially expressed utilizing the Gene Set Enrichment Analysis. Significance was assumed at a fold change > 1.5, P-value < 0.05, and FDR (false discovery rate) < 0.1. To validate the RNA-seq findings, we performed real time-polymerase chain reaction assays (n = 15 per group) for targeted genes. RESULTS: Pathway-level analysis showed that exercise significantly suppressed ubiquitin mediated proteolysis pathway (normalized enrichment scores [NES]: 1.7, P=0.01, FDR=0.09). Atrogin-1 gene expression was suppressed in the exercised group at POST9 in comparison to PRE, and POST3, and also when compared with the non-exercised group at POST9 (estimated mean difference [RYGB vs. RYGB+ET at POST9]: -1.97, CI95%=-3.0 to -0.8, P=0.01). MuRF-1 gene expression decreased after surgery and kept reduced after the intervention for both groups (main time effect: P<0.01 for both). CONCLUSIONS: Our data suggest that a 6-month, exercise training program suppresses the ubiquitin-proteasome system via the downregulation of Atrogin-1 in obese woman undergoing bariatric surgery. This may elucidate a molecular mechanism that partially explains muscle wasting following bariatric surgery and the exercise-induced hypertrophic effect in this condition.Clinicaltrials.gov: NCT02441361
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