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Volume 126, Issue 2, Pages (February 2004)

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Presentation on theme: "Volume 126, Issue 2, Pages (February 2004)"— Presentation transcript:

1 Volume 126, Issue 2, Pages 499-510 (February 2004)
Leptin reduces the development of the initial precancerous lesions induced by azoxymethane in the rat colonic mucosa  Thomas Aparicio, Sandra Guilmeau, Hélène Goiot, Annick Tsocas, Jean-Pierre Laigneau, André Bado, Iradj Sobhani, Thérèse Lehy  Gastroenterology  Volume 126, Issue 2, Pages (February 2004) DOI: /j.gastro

2 Figure 1 Pair-fed rats were treated for a week with leptin (1 mg−1 · kg−1 · day) or its vehicle, delivered by osmotic pump and implanted subcutaneously (n = 5 rats per group). (A) Body weight curves of vehicle or leptin-treated rats during experiment in comparison with untreated control Fischer 344 rats fed ad libitum. (B) Mean food intake for the time of experiment in leptin-treated rats in comparison with untreated control rats fed ad libitum.(C) Leptinemia in pair-fed vehicle-treated and leptin-treated rats. ∗P < 0.001; ∗∗P < (Student t test). Gastroenterology  , DOI: ( /j.gastro )

3 Figure 2 BrdU-labeled DNA-synthesizing cells in the rat colonic mucosa. (A) Right colon. (B) Left colon. Note in the mucosa of the right colon the occurrence of labeled cells mainly in the middle third of bifid crypts. (C) Histogram showing the labeling indices in the right and left colons. (D) Histogram showing the spatial distribution of labeled cells within the 3 equal compartments of the colonic crypt. In the rat, the major zone of DNA synthesis in the right colon corresponds to the middle third of the crypt and, in the left colon, to the lower third. ∗P = (Student t test). Gastroenterology  , DOI: ( /j.gastro )

4 Figure 3 Representative examples of Ob-R Western immunoblots obtained with M-18 antibody in right and left colonic mucosae from 4 Fischer 344 rats. The latter were systemically given by osmotic pump either leptin (1 mg−1 · kg−1 · day) or vehicle (controls) for a week. A protein band of approximatively 120 kilodaltons, corresponding to the long isoform Ob-Rb, was detected in right and left colon of each rat. Tubulin immunoblots performed on the same membrane with a tubulin antibody (Sigma) diluted 1:2000 ascertained that protein loading was equal in all lanes. Gastroenterology  , DOI: ( /j.gastro )

5 Figure 4 Leptin receptor immunoreactivity with M18 antibody in the colon of Fischer 344 rats treated with systemic leptin for 7 days. Paraformaldehyde fixation. (A and B) Right colon: (A) Ob-R is clearly expressed in the upper two thirds of crypts; the lower third, rich in mucous cells, is weakly positive. The immunohistochemical signal is located in the apical membrane and apical part of cytoplasm (golgi area) of epithelial cells (this is particularly evident in cells lining the colonic lumen; arrow) and in basolateral membranes. (B) Detail of 1 hemicrypt of the right colon showing immunoreactivity in basal (arrows) and lateral (arrowheads) membranes. (C-F) Left colon: (C) Ob-R immunoreactivity is visible in surface epithelial cells (arrow) and all along the crypts. (D) On the left is hemicrypt colon showing immunoreactivity in basal (arrow) and lateral (arrowhead) membranes. The photograh was taken without nuclei counterstaining. On the right is the same hemicrypt colon after nuclear staining; basal membranes are less visible. (E and F) Detail of apical Ob-R-immunoreactive signal in membrane (arrow) and golgi area of epithelial cells lining the colonic lumen (E) or the glandular lumen (arrow). (F) The distribution of immunoreactivity was the same in control rats having received the vehicle. It was also the same whatever the other fixateurs used, Carnoy’s or Bouin’s fluid. Bar = 20 μm. Gastroenterology  , DOI: ( /j.gastro )

6 Figure 5 Effect of intracolonic injections, through a catheter inserted into the right colon, of leptin (2 mg/kg) or vehicle, twice daily for 4 days, on the proliferation of epithelial cells in the right, middle, and left colon (n = 5 rats per group). (A) Labeling indices. (B) Histogram of distribution of labeled cells within the 3 colonic segments. No effect of leptin was noted. Gastroenterology  , DOI: ( /j.gastro )

7 Figure 6 Effect of 23 days’ administration of leptin (1 mg−1 · kg−1 · day) or vehicle by intraperitoneal miniosmotic pump in AOM-treated rats (n = 5 rats per group). (A) Plasma leptin levels in pair-fed vehicle- and leptin-treated rats. (B) Wet weights of stomach and small and large intestine in these 2 groups. (C) Lengths of small and large intestine. (D) Jejunal mucosal thickness. There was a slight but significant decrease in thickness in the leptin-treated group as compared with controls. ∗P < 0.05 (Student t test); ∗∗P < (Mann-Whitney U test). Gastroenterology  , DOI: ( /j.gastro )

8 Figure 7 (A) Examples of aberrant colonic crypts. (B) Effect of leptin plus AOM treatment on the number of ACF in the different colonic segments. Fischer 344 rats were systemically infused for 23 days with leptin (1mg−1 · kg−1 · day) or vehicle and received 2 doses of AOM (15 mg/kg) on day 0 and day 7. ∗P = 0.03; ∗∗P < 0.02; ∗∗∗P = (Student t test). Gastroenterology  , DOI: ( /j.gastro )

9 Figure 8 Effect of 1- or 3-week administration by osmotic minipump of systemic leptin or vehicle on the plasmatic levels of insulin and gastrin in pair-fed rats. ∗P = 0.03 (Student t test). The decrease in insulinemia after 3-week leptin treatment did not quite reach statistical significance (Mann-Whitney U test). Gastrinemia did not vary. Gastroenterology  , DOI: ( /j.gastro )


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