Basic-alimentary tractLeptin reduces the development of the initial precancerous lesions induced by azoxymethane in the rat colonic mucosa☆
Section snippets
Animals
Male Fischer 344 rats were obtained from Iffa-Credo (Saint Germain sur l’Arbresle, France), housed in our animal quarters in individual cages, kept in a temperature-controlled room with a 12-hour light-dark period. They were given standard rat food pellets and water ad libitum. Animals were treated in accordance with European Community guidelines concerning the care and use of laboratory animals.
Study of colonic epithelial cell proliferation
Systemic administration of leptin: Rats (mean weight 280–300 g) were anesthetized with pentobarbital
Systemic administration of leptin stimulates epithelial cell proliferation in the right but not in the left colon
During the experiment, body weight curves were similar in pair-fed leptin-treated and vehicle-treated control rats, and no significant loss in body weight was observed (−2.5% and −2%, respectively), whereas untreated control Fischer 344 rats fed ad libitum had a 5% gain in body weight (Figure 1A). However, intraperitoneal administration of leptin for a week reduced the food intake by a mean of 57% compared with these control rats fed ad libitum (Figure 1B). Note that this reduction in food
Discussion
The present study reports for the first time a significant inhibitory effect of leptin on the initial stages of carcinogenesis in the rat colon and provides new interesting data about the potential growth action of leptin on the gut, particularly on the colonic epithelial cell proliferation.
Leptin has been considered by some authors as a growth factor for small intestine20 and colonic epithelial cells.15 Actually, if there are consensual opinions about the ability of leptin to stimulate in
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Supported by the Institut de la Santé et de la Recherche médicale (INSERM) and the La Ligue contre le Cancer, Comité de Paris (No. 75-02/RS-7 to T.L.), and the Assistance Publique des Hôpitaux de Paris (to T.A.).