Intestinal adaptation for oligopeptide absorption via PepT1 after massive (70%) mid-small bowel resection

Abstract

Introduction: Proteins are absorbed primarily as short peptides via peptide transporter 1 (PepT1).

Hypothesis: Intestinal adaptation for peptide absorption after massive mid-small intestinal resection occurs by increased expression of PepT1 in the remnant small intestine and colon.

Methods: Peptide uptake was measured in duodenum, jejunum, ileum, and colon using glycyl-sarcosine 1 week (n = 9) and 4 weeks (n = 11) after 70% mid-small bowel resection and in corresponding segments from unoperated rats (n = 12) and after transection and reanastomosis of jejunum and ileum (n = 8). Expression of PepT1 (mRNA, protein) and villus height were measured.

Results: Intestinal transection/reanastomosis did not alter gene expression. Compared to non-operated controls, 70% mid-small bowel resection increased jejunal peptide uptake (p < 0.05) associated with increased villus height (1.13 vs 1.77 and 1.50 mm, respectively, p < 0.01). In ileum although villus height increased at 1 and 4 weeks (1.03 vs 1.21 and 1.35 mm, respectively; p < 0.01), peptide uptake was not altered. PepT1 mRNA and protein were decreased at 1 week, and PepT1 protein continued low at 4 weeks. Gene expression, peptide uptake, and histomorphology were unchanged in the colon.

Conclusions: Jejunal adaptation for peptide absorption occurs by hyperplasia. Distal ileum and colon do not have a substantive role in adaptation for peptide absorption.

Figure 1

Weight change expressed as percentage change in initial weight in non operated control rats at 1 wk (NC 1 wk), operated controls at 1 week (OC) and 1 week post resection rats (1 wk rsxn), and weight change in non operated control rats at 4 weeks (NC 4wk) compared to resection rats at 4 weeks (4wk rsxn). Weight change in resection group is less that OC at 1 wk, and less than non operated controls over 4 wk.

Figure 2

Carrier mediated Gly-Sar uptake at A) 1 mM and B) 5 mM Gly-Sar concentrations in the 4 anatomic segments of the intestine in non operated control (NC), operated control (OC), 1 week post resection group (1wk rsxn), and 4 weeks post resection group (4wk rsxn). Gly-Sar uptake is increased significantly 4 weeks after resection in the jejunum

Figure 3

Variations in relative cellular levels of PepT1 protein in A) proximal jejunum and distal ileum, and B) proximal colon in non operated control (NC), operated control (OC), 1 week post resection group (1wk rsxn), and 4 weeks post resection group (4wk rsxn). PepT1 protein levels are decreased in ileum after resection. No change noted in colon.

Figure 4

Variations in relative cellular levels of PepT1 mRNA in proximal jejunum, distal ileum, and proximal colon in non operated control (NC), operated control (OC), 1 week post resection group (1wk rsxn), and 4 weeks post resection group (4wk rsxn). PepT1 mRNA levels are decreased in ileum 1 wk after resection. No change noted in colon

Figure 5

Change in villous height / colonic crypt depth in the 4 anatomic segments of the intestines in non operated control (NC), operated control (OC), 1 week post resection group (1wk rsxn), and 4 weeks post resection group (4wk rsxn). Villus height is increased in jejunum and ileum after resection.