Leptin mediates a proliferative response in human gastric mucosa cells with functional receptor.
BACKGROUND
Recently, the rat stomach was reported as a source of leptin, a hormone mainly secreted by adipocytes. Also Helicobacter pylori-induced gastritis in humans was associated with locally elevated leptin levels. In addition, it was suggested that gastric leptin adjusts the function of the intestinal tract in parallel to the function of hypothalamic satiety centers.


OBJECTIVE
Here we examined the synthesis and potential physiologic role of leptin in the human stomach.


METHODS
RT-PCR was employed to detect leptin mRNA in the human stomach and the human gastric carcinoma cell line AGS while immunogold staining and electron microscopy were used to detect leptin protein. The in vitro effects of leptin on cell proliferation were examined in the AGS cell line.


RESULTS
No leptin mRNA could be detected by RT-PCR, yet immunogold labeling and electron microscopy allowed visualization of leptin protein in the human gastric mucosa. At concentrations of 100 nM, leptin led to a significantly increased BrdU-uptake in AGS cells (+27%, p < 0.017). The MAP-kinase-1-specific inhibitor U0126 blocked the leptin-induced cell proliferation in a dose-dependent fashion.


CONCLUSIONS
Leptin protein may not be produced but rather stored in human gastric cells. Leptin-induced increases in the proliferation of gastric mucosa cells suggests that leptin might contribute to mucosal integrity and gastroprotection.
Medical Department I, University Hospital Carl Gustav Carus, Technical University, Dresden, Germany.
R
R
Schneider
S R
SR
Bornstein
G P
GP
Chrousos
S
S
Boxberger
G
G
Ehninger
M
M
Breidert
D002352:Carrier Proteins / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D018076:DNA, Complementary / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D020738:Leptin / Q000378:metabolism / Q000502:physiology*; D008854:Microscopy, Electron; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D018076:DNA, Complementary; D007202:Indicators and Reagents; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012313:RNA