Impaired postprandial releases/syntheses of ghrelin and PYY(3-36) and blunted responses to exogenous ghrelin and PYY(3-36) in a rodent model of diet-induced obesity.
OBJECTIVE
This study investigated the effects of peripheral administration of ghrelin and PYY(3-36) on food intake and plasma and tissue fasting and postprandial ghrelin and PYY(3-36) levels in normal-weight (NW) and diet-induced-obese (DIO) rats.


METHODS
In experiment one, NW and DIO rats received a single intraperitoneal injection of saline, PYY(3-36) or ghrelin; food intake was measured for 4 h. In experiment two, total plasma ghrelin and PYY(3-36), gastric fundus ghrelin, and ascending colon PYY(3-36) were measured either after a 20-h fast or 2 h after refeeding in NW and DIO rats by radioimmunoassay.


RESULTS
Compared to the NW rats, findings in the DIO rats revealed: (i) a reduced sensitivity to both the anorectic effect of exogenous PYY(3-36) and the orexigenic effect of exogenous ghrelin; (ii) the postprandial plasma ghrelin levels were significantly higher; and (iii) refeeding decreased endogenous plasma ghrelin levels by 53% in the NW rats and 39% in DIO rats. Refeeding increased the plasma PYY(3-36) level by 58% in the NW rats versus 9% in the DIO rats (P=0.003).


CONCLUSIONS
Compared with regular rats, DIO rats exhibit blunted responses in food intake to exogenous ghrelin and PYY(3-36). Although endogenous ghrelin and PYY(3-36) in DIO rats are not altered in the fasting state, their responses to food ingestion are blunted in comparison with regular rats.
Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555-0632, USA.
Junying
J
Xu
Terry A
TA
McNearney
J D Z
JD
Chen
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003106:Colon / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D004435:Eating; D005215:Fasting / Q000097:blood; D005748:Gastric Fundus / Q000378:metabolism; D054439:Ghrelin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D019518:Postprandial Period; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001786:Blood Glucose; D054439:Ghrelin; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36)