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

Background and Aim: 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 4h. 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 2h 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.