Acylated (octanoylated)
ghrelin stimulates food intake and
growth hormone secretion and is deacylated into
desacyl ghrelin by
butyrylcholinesterase. Acylated and
desacyl ghrelin both promote adipogenesis.
Ghrelin concentrations decrease with
hyperglycemia and
hyperinsulinism. We hypothesized that 1) acylated
ghrelin increases during pregnancy, contributing positively to energy balance, but is lower in women with
gestational diabetes and 2)
butyrylcholinesterase activity is inversely correlated with acylated
ghrelin concentrations. In a first group of subjects, using two-site sandwich
ghrelin assays that specifically detect full-length forms, we investigated women with and without
gestational diabetes (n = 14/group) during pregnancy and after delivery. We examined whether changes in
ghrelin during a test meal were correlated with changes in
pituitary growth hormone [assessed through calculation of the area under the curve (AUC) during the test meal]. In postpartum subjects, the percent of total
ghrelin that is acylated was four to five times higher than previously observed using single antibody assays. During pregnancy, acylated
ghrelin concentrations (mean +/- SE) were lower compared with the postpartum period throughout the meal (AUC 1.2 +/- 0.2 vs. 10.2 +/- 1.9 ng.ml(-1).90 min(-1), P < 0.001). In the postpartum, acylated
ghrelin and
growth hormone were positively correlated (r = 0.50, P = 0.007). Desacyl (but not acylated)
ghrelin was increased in subjects with
gestational diabetes during and after pregnancy (AUC 15.4 +/- 1.9 vs. 8.6 +/- 1.2 ng.ml(-1).90 min(-1), P = 0.005). In a second group of subjects (n = 13), acylated
ghrelin was similarly suppressed during pregnancy. Circulating
octanoate concentrations (3.1 +/- 0.5 vs. 4.5 +/- 0.6 microg/ml, P = 0.029) and
cholinesterase activity (705 +/- 33 vs. 1,013 +/- 56 U/ml, P < 0.001) were lower during pregnancy compared with the postpartum period. In conclusion, acylated
ghrelin markedly decreases during pregnancy, likely because of a decrease in the acylation process.
Desacyl ghrelin increases in
gestational diabetes, possibly reflecting resistance to the inhibitory effect of
insulin on
ghrelin secretion.