The Unconventional Role for Gastric Volume in the Response to Bariatric Surgery for Both Weight Loss and Glucose Lowering

Abstract

Objective: To study the relationship between the amount of surgery-induced gastric volume reduction and long-term weight loss and glucose tolerance. Background Data: Vertical sleeve gastrectomy (VSG) has recently surpassed gastric bypass to become the most popular surgical intervention to induce sustained weight loss. Besides inducing significant weight loss, VSG also improves glucose tolerance. Although no clear correlation has been observed between the size of the residual stomach and sustained weight loss, this begs the question whether less aggressive gastric volume reduction may provide sufficient efficacy when weight loss is not the major goal of the surgical intervention. Methods: A series of strategies to reduce gastric volume were developed and tested in Long Evans male rats, namely: VSG, Fundal (F)-Resection, Gastric Sleeve Plication (GSP), Fundal-Plication, and Fundal-Constrained. Results: All surgical interventions resulted in a reduction of gastric volume relative to sham, but none of the interventions were as effective as the VSG. Gastric volume was linearly correlated to increased gastric emptying rate as well as increased GLP-1 response. Overall, cumulative food intake was the strongest correlate to weight loss and was logarithmically related to gastric volume. Regression modeling revealed a nonlinear inverse relation between body weight reduction and gastric volume, confirming that VSG is the only effective long-term weight loss strategy among the experimental operations tested. Conclusions: The data suggest a minimum threshold volume of the residual stomach that is necessary to induce sustained weight loss. Although all gastric volume interventions increased the GLP-1 response, none of the interventions, except VSG, significantly improved glucose tolerance. In conclusion, if weight loss is the primary goal of surgical intervention, significant volume reduction is required, and this most likely requires excising gastric tissue.

The Role of Elevated Branched-Chain Amino Acids in the Effects of Vertical Sleeve Gastrectomy to Reduce Weight and Improve Glucose Regulation

“…VSG rats had a higher glucose and valine uptake, as well as higher isotope-glucose and isotope valine uptake, at 15 and 30 min after a liquid meal. These data are consistent with increased gastric emptying rate observed after VSG ( Figure 4 ; Chambers et al, 2013 ; Evers et al, 2020 ). Potentially, the exposure of the small intestine to higher concentrations of BCAA due to increased gastric emptying may lead to the increased expression of the transporters, similar to that seen with increased dietary exposure to amino acids and other substrates ( Ferraris and Diamond, 1989 ).…”

“…At day 196, animals were fasted overnight, and on the following morning, they received a mixture of liquid meal (Ensure Plus) containing 125 mg/ml glucose + 125 mg/ml 6,6-[ 2 H]D-glucose + 12.5mg/ml [ 15 N]L-valine. VSG rats had a higher glucose and isotope-glucose excursion at 15 and 30 min after the liquid meal, which is consistent with an increased absorbance of glucose due to increased gastric emptying as a result of VSG ( Chambers et al, 2013 ; Evers et al, 2020 ; Figures 4D and 4E ) and increased absorption capacity due to upregulation of the transporters Slc7a5 and Slc7a8 ( Figure 4A ). Labeled glucose levels were lower in duodenum chyme but higher in the ileum chyme of VSG rats ( Figure 4F ).…”

The role of elevated branched chain amino acids in the potent effects of vertical sleeve gastrectomy to reduce weight and improve glucose regulation in mice

“…VSG rats had a higher glucose and valine uptake, as well as higher isotope-glucose and isotope valine uptake, at 15 and 30 minutes following liquid meal. These data are consistent with increased gastric emptying rate observed after VSG (Figure 4) (27,33). Potentially, the exposure of the small intestine to higher concentrations of BCAA due to increase gastric emptying may lead to the increased expression of the transporters, similar to that seen with increased dietary exposure to amino acids and other substrates (45).…”

“…Plasma BCAA levels spike, but decline back to baseline levels within 3 hours after consuming a protein-rich meal (38). We chose to measure the levels of BCAA under static conditions such as overnight fast, due to the differences in gastric volume and increased gastric emptying in VSG animals, which could have influence on the concentrations of plasma BCAA levels after feeding (27,33). Consequently, we may have underestimated BCAA levels in the BCAA supplemented mice.…”

“…Mice were maintained on a 60% HFD and Long Evans male rats on a 45% Tso's HFD for 8 weeks prior to undergoing Sham or VSG surgery, as described previously (33,57,58). See above for diet source and catalog numbers.…”