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Leptin in the human stomach
  1. S CINTI,
  2. R DE MATTEIS,
  3. E CERESI
  1. Institute of Normal Human Morphology-Anatomy
  2. University of Ancona, 60020 Ancona, Italy
  3. Departament de Biologia Fonamental i Ciències de la Salut
  4. Universitat de les Illes Balears, Cra. Valldemossa Km 7.5
  5. 07071 Palma de Mallorca, Spain
  6. Hospital Son Dureta, Palma de Mallorca, Spain
  7. Department of Paediatrics, University Hospital
  8. Verona University, Verona, Italy
  1. Professor A Palou.dbfapo0{at}ps.uib.es
  1. C PICÓ,
  2. J OLIVER,
  3. P OLIVER,
  4. A PALOU
  1. Institute of Normal Human Morphology-Anatomy
  2. University of Ancona, 60020 Ancona, Italy
  3. Departament de Biologia Fonamental i Ciències de la Salut
  4. Universitat de les Illes Balears, Cra. Valldemossa Km 7.5
  5. 07071 Palma de Mallorca, Spain
  6. Hospital Son Dureta, Palma de Mallorca, Spain
  7. Department of Paediatrics, University Hospital
  8. Verona University, Verona, Italy
  1. Professor A Palou.dbfapo0{at}ps.uib.es
  1. A OBRADOR
  1. Institute of Normal Human Morphology-Anatomy
  2. University of Ancona, 60020 Ancona, Italy
  3. Departament de Biologia Fonamental i Ciències de la Salut
  4. Universitat de les Illes Balears, Cra. Valldemossa Km 7.5
  5. 07071 Palma de Mallorca, Spain
  6. Hospital Son Dureta, Palma de Mallorca, Spain
  7. Department of Paediatrics, University Hospital
  8. Verona University, Verona, Italy
  1. Professor A Palou.dbfapo0{at}ps.uib.es
  1. C MAFFEIS
  1. Institute of Normal Human Morphology-Anatomy
  2. University of Ancona, 60020 Ancona, Italy
  3. Departament de Biologia Fonamental i Ciències de la Salut
  4. Universitat de les Illes Balears, Cra. Valldemossa Km 7.5
  5. 07071 Palma de Mallorca, Spain
  6. Hospital Son Dureta, Palma de Mallorca, Spain
  7. Department of Paediatrics, University Hospital
  8. Verona University, Verona, Italy
  1. Professor A Palou.dbfapo0{at}ps.uib.es

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Editor,—After the report in 1998 by Bado and colleagues1 describing the presence of leptin in rat stomach, we have recently reported the first evidence of leptin in the stomach mucosa of humans.2 It was shown that the cells in the lower half of the stomach glands were clearly immunoreactive for leptin, and both leptin mRNA and leptin protein in the human gastric epithelium were detected. Western blot analysis showed the presence of a 16 kDa band corresponding to leptin and a 19 kDa band which, as suggested for rats,1 could represent a leptin precursor. It was also shown that secretory granules of chief cells contain this hormone, suggesting that gastric leptin could function in the short term system control of feeding behaviour and that it is secreted (probably together with pepsinogen) in the stomach lumen by chief cells. Confirmation of these findings was reported by Sobhani and colleagues.3 They also showed the presence of leptin receptor in stomach epithelium, suggesting a possible paracrine pathway for leptin. Stomach leptin levels seem to be higher in humans than in rats.1 3

Interestingly, Sobhani et al have also shown3 that gastric leptin is simultaneously released into the blood and into the gastric juice by pentagastrin and secretin. They suggested that secretin has a direct effect on gastric chief cells, an idea based on the presence of secretin receptors on these cells4 and on the efficacy of secretin in stimulating pepsinogen secretion.5

However, by immunoelectron microscopy we observed2 the presence of leptin not only in chief cells but also in endocrine cells exhibiting a distinctive morphology in the basal portion of the gland. These cells showed secretory granules labelled with many leptin-gold particles.2 Its ultrastructure corresponded to the P cell type.6 7

Thus secretory granules of both endocrine and chief cells contain leptin.2 It is probably secreted in the stomach lumen by chief cells and into the stomach circulation by a special type of endocrine cell. The observation3 that intravenous infusions of pentagastrin or secretin caused an increase in circulating leptin levels and leptin release into gastric juice is in keeping with both endocrine and exocrine secretory sources. They could function in the short term system to control feeding behaviour and in the gastrointestinal lumen to regulate the availability of nutrients acting in the sites where a non-degraded form of hormone would approach.

Our observation of much lower levels of leptin immunostaining in a patient under postpandrial conditions compared with five fasted patients2 is in agreement with a likely functional response of human stomach leptin to food intake. The effects of cholecystokinin in the rat1 and of pentagastrin and secretin in humans3 stimulating emptying of stomach leptin are all strong arguments for a short term satiety role of leptin. There is also the observation that leptin interacts synergically with other short term satiety peptides.8

There is a need for further investigation in humans, with difficulties arising from ethical limitations. However, taken together, both articles2 3 on leptin in the human stomach and the previous report in rats,1 we can conclude that three important pathways (endocrine, exocrine, and autocrine) for the action of leptin are present in human stomach, where the main physiological role for this hormone is foreseen.

Acknowledgments

This work was supported by European Commission COST-918 Action from DGXII to A Palou and S Cinti; by Ancona University grants to S Cinti; by project “Physiopathology, Pharmachology and Clinical Aspects of Obesity”, to S Cinti; and by DGESIC, Secretaría de Estado de Educación, Universidades, Investigación y Desarrollo, Spain (grant PM97-0094) to A Palou.

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