Preproghrelin-derived peptide, obestatin, fails to influence food intake in lean or obese rodents.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
Our data demonstrate that peripheral administration of obestatin did not modify food intake in rats or obese mice or gastric motor function in rats.
Gourcerol
Guillaume
G
Center for Ulcer Research and Education (CURE): Digestive Diseases Research Center, and Center for Neurovisceral Sciences and Women's Health, Department of Medicine, Division of Digestive Diseases, University of California-Los Angeles, USA.
Coskun
Tamer
T
Craft
Libbey S
LS
Mayer
John P
JP
Heiman
Mark L
ML
Wang
Lixin
L
Million
Mulugeta
M
St-Pierre
David H
DH
Taché
Yvette
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology*; D005746:Gastric Emptying / Q000502:physiology; D054439:Ghrelin / Q000008:administration & dosage / Q000502:physiology*; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000502:physiology; D013851:Thinness / Q000503:physiopathology*; D054832:Urocortins / Q000502:physiology
D001786:Blood Glucose; D054439:Ghrelin; D054832:Urocortins; D013004:Somatostatin