Endocrine Abstracts

Background and aims

95% of serotonin is produced in the periphery. Serotonin system in the periphery regulates multiple physiological aspects. In previous researches that we made, using the Tph1 inhibitor - LP533401 (peripheral serotonin inhibitor) it shows that this agent could be use for treatment of obesity and obesity-induced diabetes in male Wistar rats. With current study we aimed to look more detailed in to fine mechanisms of action of serotonin related with other hormones such as ghrelin and leptin.

Materials and methods

We used forty Wistar rats separate in 2 groups- rats with induced obesity and diabetes and healthy rats (control group). Each of this groups was separated in other 2 - one with daily intraperitoneal injection of LP533401 ( 0.5 mg/kg) and one without. In 4 weeks period, we were tracking different factor- blood glucose level, insulin secretion, rats weight, blood levels of ghrelin and leptin. We measured the level of ghrelin and leptin in the beginning of the study and in the beginning of every week just before the meal.

Results

After application of LP533401, the blood levels of ghrelin starts to change. In the group with diabetic and obese rats using LP544401, the levels of ghrelin decreased of 5.4% for the first week till 12.2% in the fourth week (P<0.05), and with 9, 4% (in total) in the control group. No significant dynamic in the groups without daily intraperitoneal injection of LP533401. Also there were significantly reduction of hyperglycemia and peripheral insulin resistance and reducing body weight in the obese and diabetic rats group, but also in the control group using LP533401. In the beginning of the study, the levels of leptin were around 3 times higher in the diabetic and obese rats’ groups both using LP533401 or not. During the study, the leptin level in the diabetic and obese rats group using LP533401 decrease with 54.4% (P <0.05). In the diabetic and obese rats group in which we were not using LP533401, the levels of leptin raised with 5.4%.

Conclusion

Using LP533401 inhibitor significantly decrease fasting blood level of ghrelin in rats with induced obesity and diabetes, which corresponded with their weight loss and reduction of hyperglycemias. The level of leptin in the group whit diabetic and obese rat using LP533401, also decrease significantly together with their weight loss, which leads us to the conclusion for decreasing of leptin resistance in this group.