Endocrine Abstracts

Background and AIMS: Obesity can be caused because of reduction in energy expenditure and /or increased caloric intake. Total calorie intake has increased in recent decades, and research and studies on eating behaviour have reported increased intake of foods rich in fats and sugars. Excess calories alone increase body weight and reduce insulin sensitivity, even in healthy individuals who are not obese. In addition, increased consumption of sugars and fats is associated with weight gain and the development of insulin resistance in humans. Many regulatory pathways for food intake, including those that use serotonin as a neurotransmitter, are affected by obesity or by hypercaloric diets leading to obesity. Summarizing the data known so far, it can be said that reduced serotonergic signalling and low availability of SERT are associated with hyperphagia and obesity. Because of these facts, it is important to know how brain serotonin mediation affects food behaviour.

Materials-Methods: Ro 60-0175 is a novel 5-hydroxytryptamine (HT)(2C) (serotonin) central receptor-selective agonist that we used in our study. We used forty Wistar rats separated in 2 groups- rats with obesity and diabetes and healthy rats (control group). Each of these groups was separated in other 2 - one with a daily intraperitoneal injection (i.p.) of Ro 60-0175 (for 1 mg/kg increasing till 3 mg/kg per day) and one without. In 4 weeks period, we were tracking blood glucose levels, insulin secretion and rats’ weight.

Results: It was shown that after the application of Ro60-0175, the weight of the rats in the diabetic and obese group decreased by 5.5% (P< 0.05), and by 2.56% in the control group and no significant dynamic in the groups without daily intraperitoneal injection of Ro60-0175. In the diabetic and obese rats group in which Ro60-0175 was applied, we registered a reduction of hyperglycemia by 35.4% (P< 0.05) comparing the results before the start of using Ro60-0175, which is greater in the rats which reduce more body weight. The research also shows decreasing of insulin resistance by 42.1 % (P< 0.01) in diabetic and obese rats group using Ro60-0175.

Conclusion: Using Ro 60-0175 for the treatment of obesity and obesity-induced diabetes in male Wistar rats, Ro 60-0175 significantly reduces body weight 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