Background

Limb skeletal muscle mass losses in the year following bariatric surgery are ~15-fold greater than the loss expected during the typical aging process. Given the importance of muscle mass and strength for healthy aging, loss of muscle following bariatric surgery may have long-term consequences that outweigh the immediate metabolic benefits of rapid weight loss. Here, we have used a mouse model of bariatric surgery to test the hypothesis that surgical weight loss disrupts skeletal muscle proteostasis and reduces physical strength.

Methods

Male C57BL/6J mice with diet-induced obesity were obtained from Taconic at 16-wk of age. Mice underwent either sleeve gastrectomy (GS) or a sham surgery (laparotomy; DIO). Body composition was determined weekly, whereas ambulatory activity and grip strength were measured at 4- and 6-wk post-surgery, respectively. Changes in myofiber morphology (histology) and proteostasis (RT-PCR and Western blotting) were determined in quadriceps femoris muscles 6-wk post-surgery.

Results

Compared to DIO, surgery induced rapid weight loss in GS (-22%, p<0.01), with loss of both fat (-51%, p<0.01) and lean mass (-13%, p=0.01) 1-wk post-surgery. Although ambulatory activity was similar for GS and DIO, grip strength was reduced in GS (-10%, p=0.04). GS showed a marked increase in the number of myofibers with central nuclei, and increased expression of the atrophy-related transcripts Gadd45a, Hdac4 and Ctsl (+30%, +80%, and +41%, respectively, all p<0.05). GS also had increased mTORC1 activity compared to DIO (p70S6K phosphorylation (T389) +205%, p=0.01).

Conclusions

We show that rapid weight loss induced by bariatric surgery results in molecular and structural adaptations in skeletal muscle that contribute to reductions in strength. Further work will identify how bariatric surgery affects the contractile properties of skeletal muscle and will determine if pre-surgery interventions (such as exercise training or pharmacological therapies) can mitigate post-surgery muscle loss.