Impaired postprandial releases/syntheses of ghrelin and PYY3‐36 and blunted responses to exogenous ghrelin and PYY3‐36 in a rodent model of diet‐induced obesity

Abstract

AbstractBackground and Aim: This study investigated the effects of peripheral administration of ghrelin and PYY3‐36 on food intake and plasma and tissue fasting and postprandial ghrelin and PYY3‐36 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, PYY3‐36 or ghrelin; food intake was measured for 4 h. In experiment two, total plasma ghrelin and PYY3‐36, gastric fundus ghrelin, and ascending colon PYY3‐36 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 PYY3‐36 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 PYY3‐36 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 PYY3‐36. Although endogenous ghrelin and PYY3‐36 in DIO rats are not altered in the fasting state, their responses to food ingestion are blunted in comparison with regular rats.