Effects of a Fixed Meal Pattern on Ghrelin Secretion: Evidence for a Learned Response Independent of Nutrient Status

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Abstract
Circulating levels of the orexigenic peptide ghrelin increase during fasting and decrease with refeeding. Exogenous ghrelin administration is a potent stimulus for food intake in rodents and humans. In subjects on fixed feeding schedules, ghrelin increases before each meal, raising the possibility that anticipation of meals, in addition to effects of fasting and feeding, contributes to ghrelin secretion. To distinguish among these regulatory influences, plasma ghrelin profiles were generated in freely fed rats and in meal-fed rats trained to consume their daily calories over a 4-h period in the light phase. In freely feeding rats, plasma ghrelin levels increased to a peak of 778 +/- 95 pg/ml just before the onset of the dark. Similarly, in meal-fed rats anticipating a large meal of either chow or Ensure at their usual feeding time, plasma ghrelin increased steadily over the 2 h preceding the meal to peaks of 2192 +/- 218 and 2075 +/- 92 pg/ml, respectively. When freely fed rats were food deprived for a time equivalent to meal-fed rats, there was no peak of plasma ghrelin. In addition, eating-induced suppression of the ghrelin response differed significantly between meal-fed rats and ad libitum-fed rats receiving meals of similar size. These findings indicate that anticipation of eating, as well as fasting/feeding status, influences pre- and postprandial plasma ghrelin levels in rats. Together, these data are consistent with a role for ghrelin in the regulation of anticipatory processes involved in food intake and nutrient disposition.