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Background: Mechanical stimulation of the stretch receptors of the gastric wall can simulate the presence of indigested food leading to reduced food intake. We report the preliminary experimental results of an innovative concept of localized mechanical gastric stimulation.Methods: In a first survival study, a biocompatible bulking agent was injected either in the greater curvature (n = 8) or in the cardia wall (n = 8) of Wistar rats. Six animals served as sham. Changes of bulking volume, leptin levels and weight gain were monitored for 3 months. In a second acute study, a micro-motor (n = 10; MM) or a size-paired inactive device (n = 10; ID) where applied on the cardia, while 10 additional rats served as sham. Serum ghrelin and leptin were measured at baseline and every hour (T0-T1-T2-T3), during 3 h. In a third study, 24 implants of various shapes and sizes were introduced into the gastric subserosa of 6 Yucatan pigs. Monthly CT scans and gastroscopies were done for 6 months.Results: Weight gain in the CW group was significant lower after 2 weeks and 3 months when compared to the shame and GC (p = 0.01/p = 0.01 and p = 0.048/p = 0.038 respectively). Significant lower increase of leptin production occurred at 2 weeks (p = 0.01) and 3 months (p = 0.008) in CW vs. SG. In the MM group significant reduction of the serum ghrelin was seen after 3 h. Leptin was significantly increased in both MM and ID groups after 3 h, while it was significantly reduced in sham rats. The global device retention was 43.5%. Devices with lower profile and with a biocompatible coating remained more likely in place without complications.Conclusions: Gastric mechanical stimulation induced a reduced weight gain and hormonal changes. Low profile and coated devices inserted within the gastric wall are more likely to be integrated. [ABSTRACT FROM AUTHOR]