Leptin reduces the development of the initial precancerous lesions induced by azoxymethane in the rat colonic mucosa
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) t...
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Published in | Gastroenterology (New York, N.Y. 1943) Vol. 126; no. 2; p. 499 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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United States
01.02.2004
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Abstract | 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 (P < 0.008 to P < 0.001); 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. |
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AbstractList | 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 (P < 0.008 to P < 0.001); 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. |
Author | Sobhani, Iradj Laigneau, Jean-Pierre Tsocas, Annick Aparicio, Thomas Goiot, Hélène Bado, André Lehy, Thérèse Guilmeau, Sandra |
Author_xml | – sequence: 1 givenname: Thomas surname: Aparicio fullname: Aparicio, Thomas organization: INSERM U 410; IFR 02, Faculté de Médecine Xavier Bichat, Paris, France – sequence: 2 givenname: Sandra surname: Guilmeau fullname: Guilmeau, Sandra – sequence: 3 givenname: Hélène surname: Goiot fullname: Goiot, Hélène – sequence: 4 givenname: Annick surname: Tsocas fullname: Tsocas, Annick – sequence: 5 givenname: Jean-Pierre surname: Laigneau fullname: Laigneau, Jean-Pierre – sequence: 6 givenname: André surname: Bado fullname: Bado, André – sequence: 7 givenname: Iradj surname: Sobhani fullname: Sobhani, Iradj – sequence: 8 givenname: Thérèse surname: Lehy fullname: Lehy, Thérèse |
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References | 15578539 - Gastroenterology. 2004 Dec;127(6):1866-7; author reply 1867-8 |
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SubjectTerms | Animals Azoxymethane Carcinogens Cell Division - drug effects Colonic Neoplasms - chemically induced Colonic Neoplasms - pathology Colonic Neoplasms - prevention & control Infusion Pumps Injections Intestinal Mucosa - drug effects Intestinal Mucosa - pathology Leptin - administration & dosage Leptin - pharmacology Male Precancerous Conditions - chemically induced Precancerous Conditions - pathology Precancerous Conditions - prevention & control Rats Rats, Inbred F344 Recombinant Proteins - administration & dosage Recombinant Proteins - pharmacology |
Title | Leptin reduces the development of the initial precancerous lesions induced by azoxymethane in the rat colonic mucosa |
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