Leptin and Ob-Rb receptor isoform in the human digestive tract during fetal development.
BACKGROUND
Leptin, partially produced by the stomach, is a hormone involved in energy balance and regulation of food intake. It also regulates some digestive functions through its functional receptor Ob-Rb expressed by gastrointestinal epithelial cells.


OBJECTIVE
The objective of the study was to investigate the temporal and spatial appearance of Ob-Rb in the human digestive tract and leptin in the stomach.


METHODS
The esophagus, stomach, and intestine samples of 7- to 24-wk-old human fetuses and adult mucosae were studied by RT-PCR, immunohistochemistry, and Western blot. Leptin was measured by RIA in amniotic fluids at 16-33 wk gestation.


RESULTS
All mucosae expressed Ob-Rb (mRNA and/or protein) between 7 and 9 wk gestation. Leptin protein appeared by 8 wk in the gastric mucosa, whereas leptin mRNA was detected around 11 wk. Leptin levels in amniotic fluids were significantly higher during the second than during the third trimester. Overall, Ob-Rb immunoreactivity was higher in young fetuses, during the period corresponding to the formation of gastric buds and primitive intestinal crypts and the beginning of differentiation of epithelial cell types, than in the oldest. Leptin added to culture medium of gastrointestinal explants from 10- to 12-wk-old fetuses appeared to affect DNA synthesis as compared with controls, indicating that leptin receptor functionality was developing.


CONCLUSIONS
The strong expression of leptin, in amniotic fluid when fetuses begin swallowing then in the gastric mucosa, and the early presence of Ob-Rb in mucosae suggest a possible role for leptin, exerted endoluminally and in a paracrine pathway, in the developmental process (growth and/or maturation) of the human digestive tract.
Aparicio
Thomas
T
Institut National de la Santé et de la Recherche Médicale Unité 683, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, BP 416, Paris, Cedex 18, F-75870 France.
Kermorgant
Stéphanie
S
Darmoul
Dalila
D
Guilmeau
Sandra
S
Hormi
Khadija
K
Mahieu-Caputo
Dominique
D
Lehy
Thérèse
T
D000653:Amniotic Fluid / Q000737:chemistry; D004247:DNA / Q000096:biosynthesis; D004947:Esophagus / Q000737:chemistry; D047109:Fetal Development; D005333:Fetus / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D007422:Intestines / Q000737:chemistry; D020738:Leptin / Q000032:analysis* / Q000502:physiology; D020033:Protein Isoforms; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000502:physiology; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000737:chemistry
C515448:LEPR protein, human; D020738:Leptin; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D004247:DNA