peptide-yy and Hypertrophy

Roux-en-Y gastric bypass (RYGB) leads to a rapid remission of type 2 diabetes mellitus (T2DM), but the underlying mode of action remains incompletely understood. L-cell derived gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are thought to play a central role in the anti-diabetic effects of RYGB; therefore, an improved understanding of intestinal endocrine L-cell adaptability is considered pivotal.. The full rostrocaudal extension of the gut was analyzed in rats after RYGB and in sham-operated controls ad libitum fed or food restricted to match the body weight of RYGB rats. Total number of L-cells, as well as regional numbers, densities and mucosa volumes were quantified using stereological methods. Preproglucagon and PYY mRNA transcripts were quantified by qPCR to reflect the total and relative hormone production capacity of the L-cells.. RYGB surgery induced hypertrophy of the gut mucosa in the food exposed regions of the small intestine coupled with a doubling in the total number of L-cells. No changes in L-cell density were observed in any region regardless of surgery or food restriction. The total gene expression capacity of the entire gut revealed a near 200% increase in both PYY and preproglucagon mRNA levels in RYGB rats associated with both increased L-cell number as well as region-specific increased transcription per cell.. Collectively, these findings indicate that RYGB in rats is associated with gut hypertrophy, an increase in L-cell number, but not density, and increased PYY and preproglucagon gene expression. This could explain the enhanced gut hormone dynamics seen after RYGB.

Topics: Animals; Enteroendocrine Cells; Gastric Bypass; Glucagon-Like Peptide 1; Hypertrophy; Male; Mucous Membrane; Peptide YY; Proglucagon; Rats; Rats, Wistar

Factors leading to weight loss and weight stabilization after bariatric surgery are not fully understood. The aims of this study were to develop an animal model for biliopancreatic diversion (BPD) and to determine changes in gut hormones, malabsorption and small bowel histology postoperatively.. 2 groups of Wistar rats underwent sham and BPD surgery. Daily postoperative weights and food intake were measured. 24-hour fecal collections were performed at Day 6 and 21. Bomb calorimetry was performed to determine the fecal calorific values. At day 23, levels of peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2) were determined and small bowel biopsies were taken.. Animals in the BPD group had significant reduction in weight (P<0.001) and in food intake (P<0.001) compared to the sham group. Serum levels of PYY, GLP-1 and GLP-2 in the BPD group were significantly higher (P<0.005). Animals in the BPD group had significantly higher fecal energy content at Day 6 (P<0.001) but not at Day 21 when compared to the sham group. Small bowel histology confirmed the presence of significantly increased mitosis (P=0.03) and labelled cells (P=0.002) in the BPD animals when compared to sham.. In our animal model, the higher levels of PYY, GLP-1 and GLP-2 after BPD may be due to gut adaptation and hypertrophy and could be important in inducing and maintaining weight loss after bariatric surgery.

Topics: Animals; Biliopancreatic Diversion; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Hypertrophy; Intestines; Male; Peptide YY; Rats; Rats, Wistar