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Skeletal Muscle Function is Impaired in Mice Following Surgical Weight Loss

Limb skeletal muscle mass losses in the year following bariatric surgery are far greater than the loss of lean mass experienced by inactive persons during the typical aging process. This is a clinical concern, since loss of skeletal muscle mass may have long term effects that attenuate many of the benefits associated with marked weight loss (such as sarcopenia, frailty and loss of mobility). Here, we use a mouse model of bariatric surgery (gastric sleeve) to test the hypothesis that surgical weight loss impairs skeletal muscle function. Sixteen‐week‐old male C57BL6/J mice with diet‐induced obesity (DIO; 5.21 kCal/g, 60% fat, 20% carbohydrate, 20% protein; D12492 Research Diets) were randomized into groups receiving either gastric sleeve surgery (GS; 80% resection of the greater curvature of the stomach) or sham surgery (DIO‐sham; laparotomy). A third group of age‐matched lean mice were included as a non‐surgical, non‐obese comparison group (3.82 kCal/g, 10% fat, 70% carbohydrate, 20% protein; D12450J Research Diets). Following surgery, GS mice rapidly lost 20% of their pre‐surgery weight, reducing their initial fat mass by 53% and lean mass by 20%, as measured by EchoMRI. Loss of lean mass was associated with a reduction in grip strength six‐weeks post‐surgery (−10%, p=0.04), compared to DIO‐sham, despite regain of most of the initial lean mass losses. GS mice had reduced total energy expenditure compared to DIO‐sham, as measured by indirect calorimetry at both 22°C (−7% during the light phase, p=0.0015 and −11% during the dark phase, p=0.009) and at 28°C (−7% during the light phase only, p=0.05). No differences in ambulatory activity were observed between groups. These findings, although preliminary, suggest that bariatric surgery causes molecular adaptations in the skeletal muscle that may not be easily reversed once initial lean mass losses are restored. Further work will identify whether surgical weight loss causes alterations in protein breakdown/synthesis and other metabolic adaptations that affect long‐term skeletal muscle function.