Adaptation of ghrelin levels to limit body weight gain in the obese Zucker rat.

In this study, we measured the ghrelin, leptin, and insulin variations in lean and obese Zucker fa/fa rats during the acute phase of body weight gain. At 2 months of age, plasma insulin and leptin concentrations in fa/fa rats were, respectively, 470% and 3700% higher than in lean rats (p <0.0001). Plasma ghrelin was significantly lower (-24.6%; p <0.02) than in lean rats. At 6 months of age, ghrelin increased in both genotypes but the difference was no more significant. The inverse correlations existing between ghrelin and either body weight (BW), insulin or leptin at 2 months of age were no more observable in 6-month-old rats. At 6 months of age, the lean rats had the same body weight as the 2-month-old obese rats. In these body weight-matched rats, ghrelin was not correlated with BW but it remained negatively correlated with insulin and leptin. At the same body weight, obese rats had a much lower plasma ghrelin than lean rats (717+/-42 vs. 1754+/-83 pg/ml; p <0.0001). These data indicate that body composition rather than body weight is the primary factor for the down-regulation of the ghrelin system. This down-regulation constitutes a mechanism of defense of the organism against the development of obesity at least during the first part of life.