Leptin reduces the development of the initial precancerous lesions induced by azoxymethane in the rat colonic mucosa
| Autor: | Annick Tsocas, André Bado, J.-P. Laigneau, Thomas Aparicio, Iradj Sobhani, Thérèse Lehy, Sandra Guilmeau, Hélène Goïot |
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| Rok vydání: | 2004 |
| Předmět: |
Leptin
Male medicine.medical_specialty medicine.medical_treatment Azoxymethane Biology medicine.disease_cause Injections chemistry.chemical_compound Internal medicine medicine Animals Intestinal Mucosa Infusion Pumps Hepatology Cell growth Growth factor digestive oral and skin physiology Gastroenterology Rats Inbred F344 Recombinant Proteins Epithelium Rats medicine.anatomical_structure Endocrinology chemistry Colonic Neoplasms Carcinogens Carcinogenesis Precancerous Conditions Cell Division hormones hormone substitutes and hormone antagonists Hormone Aberrant crypt foci |
| Zdroj: | Gastroenterology. 126:499-510 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2003.11.004 |
| Popis: | Recent studies suggest that leptin, a hormone involved in food intake regulation, released into the circulation and gastrointestinal juice, may be a growth factor for intestine and may be involved in carcinogenesis; however, data are contradictory. This study investigates in rat colonic mucosa (1) the effects of hyperleptinemia on epithelial cell proliferation and development of aberrant crypts, earliest preneoplastic lesions, and (2) whether luminal leptin affects cell proliferation.Leptin (1 mg/kg/d) or vehicle was administered systemically by miniosmotic pump in Fischer 344 rats either for 7 days (BrdU-labeling indices study) or 23 days (azoxymethane-induced colonic lesions study). The effects of injections or continuous infusion of leptin into the colon were also studied.In systemic leptin-treated rats, plasma leptin levels were 4- to 5-fold increased (P0.008 to P0.001); labeling indices were higher in proximal colon than in pair-fed control rats (P = 0.006) but unaffected in distal colon. Unexpectedly, in azoxymethane-treated rats, leptin significantly inhibited aberrant crypt foci formation in the middle and distal colon compared with controls (P = 0.006). Under these conditions, plasma insulin levels were reduced by 41%-58%, but gastrin levels were unchanged. In controls, luminal immunoreactive leptin reached the colon. A 3.6-fold increase in intraluminal leptin had no effect on epithelial cell proliferation.This study provides the first evidence that leptin reduces the development of chemically induced precancerous lesions in colon, perhaps through decreased insulinemia, and thus does not support an important role for leptin in carcinogenesis promotion. Moreover, the study indicates that leptin is not a potent growth factor for normal intestine. |
| Databáze: | OpenAIRE |
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