ABSTRACT
The aim of this study was to investigate the central actions of the stable pansomatostatin peptide agonist, ODT8-SST on body weight. ODT8-SST or vehicle was acutely (1µg/rat) injected or chronically infused (5µg/rat/d, 14d) intracerebroventricularly and daily food intake, body weight and composition were monitored. In lean rats, neither acute nor chronic ODT8-SST influenced daily food intake while body weight was reduced by 2.2% after acute injection and there was a 14g reduction of body weight gain after 14d compared to vehicle (p<0.01). In diet-induced obese (DIO) rats, chronic ODT8-SST increased cumulative 2-week food intake compared to vehicle (+14%, p<0.05) and also blunted body weight change (-11g, p<0.05). ODT8-SST for 14d reduced lean mass (-22g and -25g respectively, p<0.001) and total water (-19g and -22g respectively, p<0.001) in lean and DIO rats and increased fat mass in DIO (+16g, p<0.001) but not lean rats (+1g, p>0.05) compared to vehicle. In DIO rats, ODT8-SST reduced ambulatory (-27%/24h, p<0.05) and fine movements (-38%, p<0.01) which was associated with an increased positive energy balance compared to vehicle (+50g, p<0.01). Chronic central somatostatin receptor activation in lean rats reduces body weight gain and lean mass independently of food intake which is likely related to growth hormone inhibition. In DIO rats, ODT8-SST reduces lean mass but promotes food intake and fat mass, indicating differential responsiveness to somatostatin under obese conditions.
Subject(s)
Body Weight/drug effects , Eating/drug effects , Peptide Fragments/pharmacology , Somatostatin/analogs & derivatives , Somatostatin/agonists , Weight Gain/drug effects , Animals , Diet , Injections , Male , Obesity/etiology , Obesity/metabolism , Peptide Fragments/administration & dosage , Rats , Rats, Sprague-Dawley , Receptors, Somatostatin/metabolism , Somatostatin/administration & dosage , Somatostatin/pharmacology , Thinness/metabolismABSTRACT
OBJECTIVES: Obestatin has been initially characterized as a new peptide derived from the ghrelin precursor, which suppresses food intake and inhibits the orexigenic and prokinetic actions of ghrelin when injected peripherally or centrally in lean mice. However, reproducing these data remains controversial. Reasons for the disparity may be the use of different doses, routes, and animal models. We aimed to investigate the effects of peripheral and intracisternal (IC) injection of obestatin on feeding, gastric motility, and blood glucose in rats as well as in diet-induced obese (DIO) mice. RESEARCH METHODS AND PROCEDURES: Food intake and gastric emptying of a semi-liquid caloric meal were measured after intraperitoneal (IP) injection of obestatin in rats and DIO mice. Gastric phasic motility and blood glucose were monitored in urethane-anesthetized rats after IC or intravenous (IV) injection of obestatin. RESULTS: Obestatin injected intraperitoneally at doses ranging from 0.1 to 3 mg/kg influenced neither acute food intake nor gastric emptying in rats. Obestatin injected intravenously at 0.3 or 3 mg/kg and IC at 7.5 or 30 microg/rat modified neither fasted gastric phasic motility nor blood glucose levels, while ghrelin (30 microg/kg, IV) increased and vagotomy suppressed gastric motility, and an oligosomatostatin analog (3 microg/rat, IC) decreased blood glucose. Obestatin, injected intraperitoneally (0.3 mg/kg) in DIO mice, did not alter feeding response to a fast, while urocortin 1 (10 microg/kg, IP) induced a 73.3% inhibition at 2 hours. DISCUSSION: Our data demonstrate that peripheral administration of obestatin did not modify food intake in rats or obese mice or gastric motor function in rats.
