Gastric ghrelin cell development is hampered and plasma ghrelin is reduced by delayed weaning in rats

The duration of breastfeeding has attracted much interest, as a prolonged period of breastfeeding has been shown to reduce the risk of developing obesity. The mechanism behind the reduced risk is, however, poorly understood. The novel hormone ghrelin augments appetite, promotes body weight increase and increases adiposity. The majority of circulating ghrelin emanates from endocrine cells in the oxyntic mucosa of the stomach. In newborn humans and rodents, the number of ghrelin cells is low after birth until weaning, when the cell population is greatly expanded. To date, information about the influence of weaning perturbations on ghrelin cell development is scarce. Therefore, we studied the effect of delayed weaning on gastric ghrelin expression and plasma ghrelin concentration. To this end, special food separator cages were used to prevent the pups from eating solid food, forcing them to drink milk up to 21 days of age. Gastric ghrelin expression was examined by immunocytochemistry and in situ hybridisation, and plasma concentrations were assessed by RIA. Our data showed that gastric ghrelin expression and plasma ghrelin concentration are maintained at a lower level by delayed weaning. We also found that the relation between gastric ghrelin expression and body weight was altered by delayed weaning. Thus, control rats displayed a positive correlation between ghrelin expression and body weight, while no such correlation was evident in animals with delayed weaning. We conclude that delayed weaning exerts a negative influence on ghrelin expression, and that the onset of solid food intake may trigger normal ghrelin expression. Therefore, we suggest that ghrelin may constitute a hormonal link between the duration of breastfeeding and body weight development.