Gut hypertrophy after gastric bypass is associated with increased glucagon-like peptide 2 and intestinal crypt cell proliferation.
OBJECTIVE
We aimed to determine changes in crypt cell proliferation and glucagon-like peptide-2 (GLP-2) in rodents and man after Roux-en-Y gastric bypass (RYGB).


BACKGROUND
Roux-en-Y gastric bypass results in sustained weight loss and reduced appetite with only mild gastrointestinal side effects. Glucagon-like peptide-2 released from intestinal l-cells after nutrient intake stimulates intestinal crypt cell proliferation and mitigates the effects of gut injury.


METHODS
Wistar rats underwent either RYGB (n = 6) or sham procedure (n = 6) and plasma GLP-2, GLP-1, and gut hormone peptide YY (PYY) were measured after 23 days. Biopsies from the terminal ileum were stained using the antibody to Ki67, which detects cyclins and hence demonstrates cells in the S-phase of the cell cycle. The total number of cells, number of mitosis, and number of labeled cells per crypt were counted. Obese patients (n = 6) undergoing RYGB were evaluated following a 420 kcal meal preoperatively, and 1, 3, 6, 12, and 24 months later for responses in l-cell products such as GLP-2, GLP-1, total PYY, and PYY3-36.


RESULTS
Rat GLP-2 levels after RYGB were elevated 91% above sham animals (P = 0.02). At necropsy, mitotic rate (P < 0.001) and cells positive for the antibody Ki67 (P < 0.001) were increased, indicating crypt cell proliferation. Human GLP-2 after RYGB reached a peak at 6 months of 168% (P < 0.01) above preoperative values. Area under the curve for GLP-1 (P < 0.0001), total PYY (P < 0.01), and PYY3-36 (P < 0.05) responses increased progressively over 24 months.


CONCLUSIONS
RYGB leads to increased GLP-2 and mucosal crypt cell proliferation. Other gut hormones from l-cells remain elevated for at least 2 years in humans. These findings may account for the restoration of the absorptive surface area of the gut, which limits malabsorption and contributes to the long-term weight loss after RYGB.
le Roux
Carel W
CW
Department of Metabolic Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom.
Borg
Cynthia
C
Wallis
Katharina
K
Vincent
Royce P
RP
Bueter
Marco
M
Goodlad
Robert
R
Ghatei
Mohammed A
MA
Patel
Ameet
A
Bloom
Stephen R
SR
Aylwin
Simon J B
SJ
D000328:Adult; D000818:Animals; D005260:Female; D015390:Gastric Bypass; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D053767:Glucagon-Like Peptide 2 / Q000097:blood*; D006801:Humans; D007082:Ileum / Q000166:cytology; D007413:Intestinal Mucosa / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D051381:Rats; D017208:Rats, Wistar
D053767:Glucagon-Like Peptide 2; D052216:Glucagon-Like Peptide 1