Eating Behavior and Glucagon-Like Peptide-1-Producing Cells in Interposed Ileum and Pancreatic Islets in Rats Subjected to Ileal Interposition Associated with Sleeve Gastrectomy

Ileal interposition-sleeve gastrectomy (II-SG) has been developed as a metabolic surgery based on the hindgut hypothesis. The aim of the present study was to test this hypothesis by studying the eating behavior, metabolic changes, and glucagon-like peptide-1 (GLP-1)-producing cells in rat models. Male Sprague-Dawley rats were subjected to laparotomy, II, SG, or II-SG. Eating behavior and metabolic parameters were monitored by an open-circuit indirect calorimeter designed for a comprehensive laboratory animal monitoring system. GLP-1-producing cells were examined by quantitative immunohistochemistry. After II alone, satiety ratio, i.e., intermeal interval/meal size, was reduced, while calorie intake was increased at 2 and 6 weeks postoperatively. Respiratory exchange ratio, VCO2/VO2, was increased to above 1.0 (i.e., carbohydrate metabolism) during both daytime and nighttime at 2 weeks postoperatively. After SG alone, GLP-1-producing cells were increased in the pancreatic islets (in terms of volume density), but not in the ileum (number/mm). After II-SG, the rate of eating was reduced, while meal duration (min) was increased during both daytime and nighttime at 2 weeks postoperatively. GLP-1-producing cells were increased by about 2.5-fold in the interposed ileum and also increased to the same extent in the pancreatic islets as seen after SG alone. The increased GLP-1-producing cells in the pancreatic islets after SG or II-SG were located around the insulin-producing beta cells. The present study provides evidence supporting the hindgut hypothesis. II-SG increased GLP-1 production both in the interposed ileum and in the pancreatic islets, leading to metabolic beneficial effects and altered eating behavior.