Peptide YY Induces Intestinal Proliferation in Peptide YY Knockout Mice With Total Enteral Nutrition After Massive Small Bowel Resection

Objective: In previous research, peptide YY (PYY) administered in supraphysiological doses did not induce significant proliferative effects in rats that were allowed to feed ad libitum after massive small bowel resection (SBR). The main reason may well have been the interference of endogenous PYY released from L cells in the distal bowel in response to the presence of augmented unabsorbed intraluminal nutrients. The purpose of the present study was to explore the effect of PYY on intestinal proliferation with total enteral nutrition (TEN) in a SBR model of PYY knockout (Pyy(-/-)) mice, which do not produce endogenous PYY. Materials and Methods: Pyy(-/-) mice were assigned into 3 experimental groups: sham mice (sham group) underwent bowel transection and reanastomosis, and received TEN; SBR mice (SBR group) underwent a 50% small bowel resection, and received TEN; and SBR-PYY mice (SBR-PYY group) underwent a 50% small bowel resection, received TEN, and were treated with PYY1-36 subcutaneously from day 2 postoperatively. Parameters of enterocyte proliferation and apoptosis were determined on day 8 following operation. Results: SBR-PYY mice demonstrated a significant increase in (vs SBR) bowel and mucosal weights, mucosal DNA and protein, villus height, and crypt depth in jejunum and ileum. SBR-PYY mice also showed an increased crypt cell proliferation index in jejunum and ileum and decreased villus cell apoptotic index in ileum compared with SBR animals. Conclusions: In an SBR model of Pyy(-/-) mice, PYY induces proliferation of residual intestine with TEN. JPGN 48:517525, 2009.