Effect of centrally and peripherally administered obestatin on food and water intake in rats

ABSTRACT

This work was designed to study the effects of acute obestatin administration on food and water intake, as well as on body weight in rats. In addition, the effect of blocking the efferent cholinergic vagal fibers on food intake was also tested in search for a possible mechanism of action. The study was carried out on 48 adult male rats with weight ranging from [185-200] grams and was divided into 3 sections. Section A intracerebroventricular [ICV] injection consisted of 24 rats that were divided into 4 groups [6 / group]. Rats in group 1 served as control and were injected with ICV saline. Rats in groups 2, 3, 4 were injected ICV obestatin in doses 15, 25, 50 nM/kg, respectively. Section B intraperitoneal injection Which included 24 rats divided into 4 groups [6 / group]. Rats in group 1 were injected with IP saline [control group]. Obestatin was injected by IP route in the other groups 2, 3, 4 in doses of 50, 100, 1000 nM/ kg, respectively. Cumulative water and food intake were monitored at 1, 3, 6 and 24 hours after both ICV and IP obestatin injection and were expressed per rat. Plasma osmolality was measured at 3 and 6 hours after ICV and IP obestatin injection. The differences in body weight of rats were recorded at the end of 24 hours. Section C rats in the 2 groups injected with the highest doses of obestatin [50 nM/kg ICV and 1000 nM/kg IP] were selected the following day and pretreated with atropine sulphate IP in a dose of 500 ug/kg.15 minutes before they were reinjected with obestatin in the same doses used in the previous day. Food and water intake were assessed after 3 hours of injection. ICV and IF injection of obestatin revealed a significantly lower water intake versus the control that appeared at 3 hours after ICV [15 nM/kg obestatin] and also at 3 hours after IP [100 nM/kg obestatin]. With higher doses of obestatin injection [ICV 25 and 50 nM/kg and IP 1000 nM/kg] the inhibition of water intake showed a significant dose dependant effect at 1 and 3 hours. Plasma osmolality showed no significant difference when compared between the studied groups after both ICV and IP obestatin injections at 3 and 6 hours. The inhibition of food intake occurred only at 3 hours with the highest doses of obestatin injected [ICV 50 nM/kg and P 1000 nM/kg] compared with the control group. No significant differences were detected in water and food intakes and also in body weight differences after 24 hours compared with the control after obestatin injection by either ICV or P routes. As regards testing the possible involvement of vagal efferent cholinergic mechanism in obestatin's action, the groups injected with the highest doses of obestatin [50 nM/kg ICV and 1000 nM/kg IP] 15 minutes after atropine premedication as well as the non pretreated groups showed a significant decrease of water and food intake at 3 hours compared with the control group. Furthermore, there were no statistically significant differences between atropine pretreated and non pretreated groups injected by the highest obestatin doses as regards food and water intake. Obestatin primarily has an effect to inhibit thirst after acute administration probably by an effect on one of the circumventricular organs. It has a weaker effect on food intake. may be because it has to diffuse to food regulating centers in the brain or because the food intake is regulated by several peptides that may antagonize each other. The vagus efferent cholinergic mechanism has no role in the inhibitory effect of obestatin on food intake. Obestatin should gain more attention as a peptide regulating water balance rather than food intake and its effect on angiotensin II and vasopressin should be investigated