Post-Surgical Effects of Roux-En-Y Gastric Bypass on Glucose Homeostasis, Intestinal Morphology and L-Cells in Obese Gottingen Minipigs

Background: Roux-en-Y gastric bypass (RYGB) is currently the most effective treatment of morbid obesity in man. In rodents, RYGB leads to a number of morphological changes in the intestine. However, little is known about the effect of RYGB surgery on intestinal morphology and enteroendocrine L-cells in larger animals and man. Here we performed RYGB surgery in obese Gottingen minipigs, to assess whether the intervention is associated with changes in intestinal volume, L-cell number and plasma levels of glucose, insulin, glucagon-like peptide-1 (GLP-1) and leptin. Methods: The study included five RYGB operated and three nonoperated obese Gottingen minipigs (body weight 99 ± 7.7 kg). Plasma samples were obtained for assessment of glucose, insulin, GLP-1 and leptin pre- and post- RYGB surgery. The pigs were euthanized eight to nine months post-surgery and the gut processed for stereological assessments of intestinal volume and L-cell number. Results: RYGB led to a sustained reduction of body weight of ~14% in two animals (responders), whereas three animals regained body weight to pre-surgical levels (non-responders). Postprandial plasma levels of glucose and insulin were unchanged in all animals post-surgery, whereas postprandial GLP-1 levels increased in both responders and non-responders and leptin levels decreased with the most pronounced improvement in responders. Variations in body weight loss were reflected in changes in length of alimentary limb, intestinal volume and total L-cell number of the alimentary limb. Conclusion: Body weight loss following RYGB surgery in obese Gottingen minipigs is associated with an increase in intestinal volume, total L-cell number, and postprandial plasma GLP-1 levels. These changes are most pronounced in the alimentary limb suggesting that the changes here may be a key determinant to the success of RYGB surgery.