Starvation, leptin and epithelial cell proliferation in the gastrointestinal tract of the mouse.
OBJECTIVE
Leptin, the ob/ob gene product, is a recently discovered peptide hormone, secreted by adipocytes, which can act as a satiety factor to regulate food intake. Its levels thus will be related to the presence of food in the lumen of the gut, and food intake is one of the most potent stimuli for intestinal epithelial cell proliferation. Leptin has a variety of other actions and the aim of this study was to see if one of these was to stimulate mucosal growth.


METHODS
Three groups of mice were fed ad libitum, starved for 48 h or starved for 48 h and given twice-daily intraperitoneal injections of recombinant leptin (1 microg/g).


RESULTS
Starvation led to a 20% decrease in body weight and a similar decrease in the weights of the intestines. Starvation also markedly inhibited intestinal epithelial cell proliferation. Leptin had little effect on the small intestine and did not stimulate proliferation. However, in the hind gut it was associated with small but significant decreases in caecal weight, distal colon mitotic counts (p = 0.036) and in colonic crypt area (approximately 20%, p<0.001).


CONCLUSIONS
Leptin did not stimulate intestinal cell proliferation, however it did have a paradoxical inhibitory action on the caecum and colon.
Chaudhary
M
M
Department of Histopathology, Division of Investigative Science, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Mandir
N
N
FitzGerald
A J
AJ
Howard
J K
JK
Lord
G M
GM
Ghatei
M A
MA
Bloom
S R
SR
Goodlad
R A
RA
D000818:Animals; D001835:Body Weight; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D011994:Recombinant Proteins; D013217:Starvation / Q000378:metabolism / Q000473:pathology*
D020738:Leptin; D011994:Recombinant Proteins