Endocrine Abstracts

Background and aims: Obesity can be cause because of reduction in energy expenditure and /or increased caloric intake. Total calorie intake has increased in recent decades and studies on eating behavior have reported increased intake of foods rich in fats and sugars. Many regulatory pathways for food intake, including those that use serotonin as a neurotransmitter, are affected by obesity or by hypercaloric diets. Summarizing the data known so far, it can be said that reduced serotonergic signaling and low availability of SERT are associated with hyperphagia and obesity. In addition, obesity has increased eating motivation and decreased D2/3 receptor binding, and lower DAT binding can be detected as well. Because of these facts, it is important to know brain serotonin mediation.

Materials and methods: WAY-163909 is a novel 5-hydroxytryptamine (HT)(2C) (serotonin) receptor-selective agonist that we used in our study. We used forty Wistar rats separate in 2 groups-rats with obesity and diabetes and healthy rats (control group). Each of this groups was separated in other 2 - one with daily intraperitoneal injection (i.p.) of WAY-163909 (for 1 mg/kg increasing till 32 mg/kg, 1 mg/kg per day) and one without. In 4 weeks period we were tracking blood glucose level, insulin secretion and rats weight. The differences in the mean values among the groups are greater than would be expected by chance; there is a statistically significant difference (P=<0.001) using SPSS program.

Results: It was shown that after application of WAY-163909, the weight of the rats in diabetic and obese group rats decreased by 55.2% (P<0.05), and by 25.3% (P<0.05) in the control group using and no significant dynamic in the groups without daily intraperitoneal injection of WAY-163909. In the diabetic and obese rats group in which WAY-163909 was applied we had registered reduction of hyperglycemia (blood glucose over 7.0 mmol/l) by 35.4% (P<0.05) compering the results before the start of using WAY-163909, which is greater in the rats which reduce more body weight. The research also shows decreasing of insulin resistance by 42.3 % (P<0.05) in diabetic and obese rats group using WAY-163909.

Conclusion: Using WAY-163909 for treatment of obesity and obesity-induced diabetes in male Wistar rats, WAY-163909 significantly reduces body weightm hyperglycemia and peripheral insulin resistance. In the study was registered reducing of body weight not only in the obese and diabetic rats group, but also in the control group.