Characterization of Adaptive Hyperplasia of the Intestines Following Roux-En-Y Gastric Bypass and Vertical Sleeve Gastrectomy in Rats

Abstract

Bariatric surgery is currently the only treatment for obesity that is effective in both the short and long term. Despite this, little is known about the mechanisms through which these surgeries act. While no single critical system has yet been identified, a number of major hypotheses have been proposed. One hypothesis is that adaptive hyperplasia of the intestines following Roux-en-Y gastric bypass (RYGB) surgery is required in order to receive the beneficial effects of the surgery. In this thesis I characterized the adaptive response of the intestines following RYGB and showed that significant hyperplasia occurs in the intestinal mucosa. In addition, I characterized the proliferation of enteroendocrine cells. I found that there is an increase in the number, but not density, of glucagon-like-peptide 1, neurotensin, and serotonin releasing cells, as well as an increase in both number and density of cholecystokinin releasing cells, in the Roux and common limbs following RYGB. This could link adaptive hyperplasia to increased circulating levels of these hormones, which has been implicated in a reduction of food intake and an improvement in glucose homeostasis. A second hypothesis that has been proposed states that RYGB and vertical sleeve gastrectomy (VSG), two similar but ultimately different surgeries, work through a common mechanism of action. In contrast to our observations in rats following RYGB, we found that adaptive hyperplasia is absent following VSG. This leads to the conclusion that either RYGB and VSG share a common mechanism that does not involve adaptive hyperplasia of the intestines, or they do not share a common mechanism.