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 ga stritis in humans was associated with locally elevated leptin levels. In ad dition, it was suggested that gastric leptin adjusts the function of the in testinal tract in parallel to the function of hypothalamic satiety centers. Aims: Here we examined the synthesis and potential physiologic role of lep tin in the human stomach. Methods: RT-PCR was employed to detect leptin mRN A in the human stomach and the human gastric carcinoma cell line AGS while immunogold staining and electron microscopy were used to detect leptin prot ein. The in vitro effects of leptin on cell proliferation were examined in the ACS cell line. Results: No leptin mRNA could be detected by RT-PCR, yet immunogold labeling and electron microscopy allowed visualization of lepti n protein in the human gastric mucosa. At concentrations of 100 nM, leptin led to a significantly increased BrdU-uptake in ACS cells (+ 27%, p < 0.017 ). The MAP-kinase-1-specific inhibitor U0126 blocked the leptin-induced cel l proliferation in a dose-dependent fashion. Conclusions: Leptin protein ma y not be produced but Father 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.