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. 2000 Aug;47(2):178–183. doi: 10.1136/gut.47.2.178

Leptin secretion and leptin receptor in the human stomach

I Sobhani 1, A Bado 1, C Vissuzaine 1, M Buyse 1, S Kermorgant 1, J Laigneau 1, S Attoub 1, T Lehy 1, D Henin 1, M Mignon 1, M Lewin 1
PMCID: PMC1727985  PMID: 10896907

Abstract

BACKGROUND AND AIM—The circulating peptide leptin produced by fat cells acts on central receptors to control food intake and body weight homeostasis. Contrary to initial reports, leptin expression has also been detected in the human placenta, muscles, and recently, in rat gastric chief cells. Here we investigate the possible presence of leptin and leptin receptor in the human stomach.
METHODS—Leptin and leptin receptor expression were assessed by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR), and western blot analysis on biopsy samples from 24 normal individuals. Fourteen (10 healthy volunteers and four patients with non-ulcer dyspepsia and normal gastric mucosa histology) were analysed for gastric secretions. Plasma and fundic mucosa leptin content was determined by radioimmunoassay.
RESULTS—In fundic biopsies from normal individuals, immunoreactive leptin cells were found in the lower half of the fundic glands. mRNA encoding ob protein was detected in the corpus of the human stomach. The amount of fundic leptin was 10.4 (3.7) ng leptin/g mucosa, as determined by radioimmunoassay. Intravenous infusions of pentagastrin or secretin caused an increase in circulating leptin levels and leptin release into the gastric juice. The leptin receptor was present in the basolateral membranes of fundic and antral gastric cells. mRNA encoding Ob-RL was detected in both the corpus and antrum, consistent with a protein of ~120 kDa detected by immunoblotting.
CONCLUSION—These data provide the first evidence of the presence of leptin and leptin receptor proteins in the human stomach and suggest that gastric epithelial cells may be direct targets for leptin. Therefore, we conclude that leptin may have a physiological role in the human stomach, although much work is required to establish this.


Keywords: leptin; leptin receptor; human stomach; gastrin; secretin

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Figure 1  .

Figure 1  

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Leptin immunostaining in normal human fundic mucosa (Bouin's fixed, paraffin embedded tissue sections). (A) Leptin immunoreactive cells are present in the lower half of the fundic epithelial glands. (B) High magnification of leptin containing cells: leptin immunostaining was visible in the canaliculi of the parietal cells (arrows). (C) Serial section of the same region: no immunoreactivity after adsorption of the antiserum with 40 µg/ml of leptin fragment (137-156).

Figure 2  .

Figure 2  

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Effect of secretin on leptin secretion into the gastric juice and blood (A), and individual integrated gastric leptin outputs (B) after pentagastrin or secretin infusion in humans. The solid line represents the median value in each group. Median (range) values are: control 18.8 (10.7-61.2) ng/h; pentagastrin 107 (39-150) ng/h; and secretin 1009 (940-1640) ng/h.

Figure 3  .

Figure 3  

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Sephadex G-100 elution profiles after incubation of 125I labelled human leptin with or without pentagastrin stimulated gastric juice (pH 1.8) for 30 minutes at 37°C. A typical experiment is shown; the three experiments performed show a single peak under both sets of conditions.

Figure 4  .

Figure 4  

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Leptin receptor immunostaining in normal human gastric mucosa. Tissues sections were fixed in Bouin's solution and embedded in paraffin. Nuclei were counterstained with Mayer's haemalum. (A) Fundic mucosa and (C) antral mucosa. Immunostaining was detected in superficial and pit epithelial mucous cells in the two mucosae and in fundic parietal cells; (B) and (D) are adjacent sections. The signal is much weaker and even absent if the antibody is adsorbed with the antigen. (E) Detail of immunostaining located on the lateral and particularly the basal (arrows) membranes in superficial and crypt mucous cells. (F) Detail of parietal cells; a strong signal is visible in sections of microcanaliculi.

Figure 5  .

Figure 5  

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Leptin and leptin receptor expression in the human stomach. (A) Reverse transcription-polymerase chain reaction (RT-PCR) analysis of mRNA: lane 1, marker ladders; lane 2, leptin mRNA in fundic epithelium; lane 3, leptin receptor mRNA; lane 4, reverse transcriptase omission. Expected sizes for PCR products: 224 bp for leptin and 246 bp for human leptin receptor. (B) Western blot of leptin receptor with antibodies K-20 and C-20 in fundic (F) and antral (A) extracted total proteins from human gastric biopsies and from rat brain (Br) as a positive control. A representative immunoblot with antibody K-20 is shown. One leptin receptor immunoreactive band with a molecular size of about 120 kDa was detected.

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