| Objective: To observe the impact of exogenous nesfatin-1 on the food intake, daily body weight and emptying rate, and to detect the concentration of nesfatin-1 in peripheral blood serum. To determine the change trend of intragastric pressure and difference of relative expressions of NUCB2 mRNA between stomach and duodenum following treatment with several doses of nesfatin-1, moreover, to explore the influence of nesfatin-1 on gastric motility in obese rats.Methods: Obese rats and normal rats underwent external jugular vein cannulation surgery after obese rat model was established. Afterwards, the postsurgerical rats were assigned into many groups respectively. The control groups were injected with 0.9% saline while the nesfatin-1 groups were treated with 100μg·kg-1 exogenous nesfatin-1, and all treatments lasted for 7 days via jugular vein, during this administration period, food intake and body weight were recorded. After administration, the rate of gastric emptying was determined through oral gavage of Phenol red. Blood had been collected daily via orbital vein, and concentrations of nesfatin-1 in serum were detected through ELISA kits. For intragastric pressure, home-made water sac was inserted into the stomach of rats, and the intragastric pressure was detected through the pressure sensor. After administration of nesfatin-1, rat was observed for 6 to 8 hours, and the intragastric pressure was recorded in time.Result: After a high fat diet treatment for eight weeks, the Lee’s indexes were 314.22±1.80 and 314.14±2.23 for normal control group and normal nesfatin-1 group respectively, the indexes were 318.22 ±1.39 and 319.03±1.24 for obese control group and obese nesfatin-1 group respectively, and the difference was statistically significant(T-test, P<0.01), so the obese rat model was established successfully. After a treatment for consecutive 7 days, the average food intake and body weight of nesfatin-1 group were less than the control group, and the loss of food intake and the decrease of body weight were more obvious in obese group. As well-known, the rate of gastric emptying was negatively correlated with the amount of Phenol red excreted from the stomach. In normal control group and normal nesfatin-1 group, the rates of gastric emptying were 64.71±4.51 and 46.47±3.20, respectively. For obese control group and obese nesfatin-1 group, the rates were 75.67±2.47 and 50.88±3.07, respectively. So it was pretty obvious that large peripheral dose of exogenous nesfatin-1 would decrease the rate of gastric emptying significantly(T-test, P<0.01). Obese rats was significantly higher than that of normal rats about the level of peripheral circulating NUCB2/nesfatin-1 concentration. Obese rats was significantly higher than that of normal rats about the expression of NUCB2 mRNA in gastric tissue. Intravenous injection of exogenous nesfatin-1 can inhibit gastric motility in Obese rats.Conclusion: Large peripheral dose of exogenous nesfatin-1 could suppress the gastric emptying function, and decrease the body weight and food intake of rats. The concentration of nesfatin-1 in peripheral serum was positively correlated with the Lee’s index. Rats of normal group remained constant level of NUCB2/ nesfatin-1 with circadian rhythms. However, disorder of peripheral NUCB/2 nesfatin-1 without circadian rhythms was the main reason of obesity, and expression of NUCB2 mRNA in stomach was strongly related to nutritional metabolism in rats. In a word, intravenous injection of exogenous nesfatin-1 would down regulate the expression of endogenous NUCB2 mRNA.
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