PROTEIN RESTRICTION AUGMENTS WEIGHTLOSS AND GLUCOSE CONTROL FOLLOWING SLEEVE GASTRECTOMY
Julia Illiano*, Luiz Lopez, Odin Schaepkens, Dudley Lamming, David Harris
Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI
Introduction: Sleeve gastrectomy (SG) improves obesity and Type 2 diabetes (T2D). The added therapeutic potential of post-operative dietary interventions on obesity and T2D are understudied. Following SG, patients increase dietary protein consumption, however, protein restriction induces weight loss, improves metabolic health, and extends lifespan in mice and humans. We hypothesized reducing dietary protein intake following SG would improve post-operative weight loss, glucose tolerance, and metabolism.
Methods: Sixty-four, C57BL/6J mice were preconditioned on high-fat, western diet (WD) starting at 5 weeks of age. At 17 weeks, mice were weight-matched and received SG or sham surgery. After recovery, mice were placed into 1 of 4 dietary groups: High (36%), medium (21%), low protein (7%), or WD. All protein diets were isocaloric. A separate control group of 16 mice were preconditioned on normal chow diet (NCD; 5% fat, 24% protein), received SG or sham, and were maintained on NCD. Weights and food intake were tracked longitudinally. Glucose tolerance and insulin sensitivity were assessed via oral glucose and insulin tolerance testing, respectively. Body composition was determined through MRI spectroscopy. Energy expenditure (EE) was quantified using indirect calorimetry and normalized to lean mass. Grip strength was assessed using an inverted cling assay. Area under the curve analysis, one-way ANOVA with Dunnett corrections, and t-tests were used.
Results: SG induced weight loss across all groups compared to their respective Shams. SG mice on 7% protein had higher percent weight loss compared to other SG groups (Figure 1A) despite having increased daily food intake compared to SG mice on 36% protein (p=0.02) or WD (p=0.01). SG mice on 36% protein and NCD had the lowest fat mass (Figure 1B) and 36% SG mice had significantly elevated lean mass (Figure 1C) compared to other SG groups. Notably, 7% SG mice had equivalent lean mass to NCD and 21% SG groups. All SG mice had improved glucose tolerance compared to their respective shams (Figure 1D). 7% SG mice trended toward improved glucose tolerance and had significantly reduced fasting glucose compared to all SG groups (Figure 1E). This occurred independent of changes in insulin sensitivity, which was similar across all groups (Figure 1F). EE was increased in all mice consuming 36% compared to 7% protein in light and dark cycles. EE did not differ between sham and SG mice within the same diet group. Cling time did not differ between sham and SG mice in any diet group or when comparing 36% and 7% SG mice.
Conclusions: Protein restriction enhances weight loss and improves T2D control after SG. This occurs independent of changes in insulin sensitivity and has minimal effects on overall lean mass or grip strength. Controlling protein consumption may improve metabolic health outcomes for patients following SG.
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