Impaired intestinal cell proliferation and cell death in leptin-deficient obese mice.
BACKGROUND
After massive small-bowel resection and loss of absorptive capacity, residual intestine has compensatory ability to adapt by cellular hyperplasia and increased absorptive function. Growth factors have been shown to enhance intestinal adaptation, but the mechanisms involved are not well defined. Leptin has been shown to function as a trophic factor in the intestine and enhances carbohydrate absorption after small-bowel resection. Therefore, we hypothesized that leptin deficiency may impair the adaptive response by modulating cellular proliferation or cell death after small-bowel resection.


METHODS
Twelve-week-old male lean control (C57BL/6J, n = 28) and leptin-deficient (Lep(ob), n = 24) obese mice underwent sham laparotomy, intestinal transection, or 50% proximal small-bowel resection. Mice were killed at 48 hours postresection, and remnant intestine was harvested. Phenotypic analysis to assess adaptation included characterization of cell proliferation (percentage BrdU incorporation), apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nickend labeling assay), and morphometric response (villus height, crypt depth).


RESULTS
The percentage S-bromodeoxyuridine (BrdU) incorporation and apoptotic indices of obese transected mice were significantly lower than lean transected mice (7.3 vs 21.9% and 0.70 vs 1.53% respectively, p < .05). In resected animals, the percentage BrdU incorporation and apoptotic indices of obese resected mice were significantly lower than for lean resected (6.1 vs 22.0% and 0.93 vs 1.80% respectively, p < .05). No differences between groups, regardless of surgery, were identified in villus height or crypt depth.


CONCLUSIONS
Therefore, we conclude that leptin deficiency impairs both cell proliferation and cell death in the early adaptive period after either small-bowel transection or resection.
Kiely
James M
JM
Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Noh
Jae H
JH
Pitt
Henry A
HA
Swartz-Basile
Deborah A
DA
D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D007421:Intestine, Small / Q000166:cytology / Q000254:growth & development / Q000601:surgery*; D020738:Leptin / Q000172:deficiency* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese
D020738:Leptin