L. Ying1, G. Breuer1, M. Hubbard1, J. Hwa1, G. Nadzam1, K. Martin1 1Yale University School Of Medicine,New Haven, CT, USA
Introduction: Sleeve gastrectomy with ileal transposition (SGIT) is superior to sleeve gastrectomy (SG) for promoting weight loss in rat and porcine models, and for preventing weight gain in a mouse model of diet-induced obesity. However, it is unknown if SGIT is superior to SG for promoting weight loss and lowering blood glucose in obese mice, and its weight loss mechanism is unclear.
Methods: SGIT was performed on a Pilot Cohort of 5 C57Bl/6J mice (7-8 weeks old), which were followed for 10 weeks to test viability. Whole transcriptome sequencing (RNAseq) was performed on the transposed ileal segments of these mice to identify highly expressed genes potentially responsible for weight loss. Next, SGIT, SG, or sham surgery (SH) was performed on a Study Cohort of 16-week old obese C57Bl/6J mice (40-45 grams, n=12 each). Prior to surgery, mice were grouped to match initial weight and fasting blood glucose. After surgery, mice were fed a low-fat diet and weighed weekly. 4 weeks after surgery, food intake was measured by weighing food over 4 days. 6 weeks after surgery, fasting blood glucose was re-measured. Additionally, after administering a liquid diet bolus via oral gavage, postprandial serum Peptide YY was measured after 15-minutes, 30-minutes, 1-hour, and 2-hours with competitive enzyme immunoassay.
Results: The overall mortality in the Study Cohort was 0%. In the Study Cohort, SGIT mice lost significantly more weight than SG or SH mice (6-week weight in grams±standard error of mean (sem): SH: 35.7±1.1, SG: 31.9±0.7, SGIT: 25.2±0.9). 4 weeks after surgery, SGIT mice consumed significantly less food than SG or SH mice (daily food intake in grams±sem: SH: 3.8±0.3, SG: 2.4±0.4, SGIT: 1.9±0.5). Fasting blood glucose (mg/dl±sem) was not statistically different between SG (77.8±8.6) and SGIT (87.7±7.7) mice 6 weeks after surgery, but both were significantly lower compared to SH mice (134.8±3.7). RNAseq of the transposed ileum from the Pilot Cohort revealed high expression of the ileal brake Peptide YY (PYY). Consequently, postprandial serum PYY was measured 6 weeks after surgery in the Study Cohort. Fasting serum PYY was not significantly different between the three groups. However, after administering a bolus of liquid diet, serum PYY rose more rapidly in SGIT mice than in SG or SH mice (graphic).
Conclusion: In this study, we show that SGIT is superior to SG for promoting weight loss, and similarly effective for lowering fasting blood glucose. SGIT mice also consume less food than SG or SH mice. An early release of Peptide YY, confirmed directly via serum measurement, provides a potential mechanistic explanation for the enhanced weight loss observed in SGIT mice.
