Early alterations in plasma ghrelin levels in offspring of calorie-restricted rats during gestation may be linked to lower sympathetic drive to the stomach

Serum ghrelin concentration is generally reduced in obesity. We aimed to assess whether this alteration is present in rats predisposed to obesity because of moderate undernutrition during gestation, and to explore whether this could be related with alterations in stomach sympathetic innervation, which is involved in gastric ghrelin secretion. Offspring of control and 20% gestational calorie-restricted dams (CR) exposed to normal-fat-diet from weaning onward were studied. Circulating ghrelin levels were measured at 25 days and 4 months of age. Morphometry, number of ghrelin-positive (ghrelin+) cells, ghrelin mRNA and protein levels, and tyrosine hydroxylase (TH) protein levels in stomach were determined at 25 days. Adult CR male animals, but not females, exhibited greater body-weight (BW) than their controls, but both males and females showed lower circulating ghrelin levels. This alteration in ghrelin levels was already present at 25 days, prior to any difference in BW. At this juvenile age, no differences in gastric morphometry, number of ghrelin+ cells or ghrelin mRNA/protein levels were found between control and CR animals, however, CR animals showed lower TH stomach content. These results suggest that circulating ghrelin concentration is early altered in rats prenatally programmed to develop obesity. This does not seem to be associated with lower ghrelin production capacity but with specific alterations in sympathetic drive to the stomach.

► We studied ghrelin in rats programmed to obesity due to maternal calorie restriction.
► Blood ghrelin levels were reduced at 25 days, prior to any alteration in body weight.
► Gastric sympathetic innervation, which is involved in ghrelin secretion, was examined.
► Gastric tyrosine hydroxylase was reduced suggesting lower sympathetic innervation.
► Reduced ghrelin levels seem to be linked with lower sympathetic drive to the stomach.