Acylated ghrelin concentrations are markedly decreased during pregnancy in mothers with and without gestational diabetes: relationship with cholinesterase

Abstract

Tham E, Liu J, Innis S, Thompson D, Gaylinn BD, Bogarin R, Haim A, Thorner MO, Chanoine JP. Acylated ghrelin concentrations are markedly decreased during pregnancy in mothers with and without gestational diabetes: relationship with cholinesterase. Am J Physiol Endocrinol Metab 296: E1093-E1100, 2009. First published February 24, 2009 doi:10.1152 doi:10. /ajpendo.90866.2008 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 ϭ 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 Ϯ SE) were lower compared with the postpartum period throughout the meal (AUC 1.2 Ϯ 0.2 vs. 10.2 Ϯ 1.9 ng ⅐ ml Ϫ1 ⅐ 90 min Ϫ1 , P Ͻ 0.001). In the postpartum, acylated ghrelin and growth hormone were positively correlated (r ϭ 0.50, P ϭ 0.007). Desacyl (but not acylated) ghrelin was increased in subjects with gestational diabetes during and after pregnancy (AUC 15.4 Ϯ 1.9 vs. 8.6 Ϯ 1.2 ng ⅐ ml Ϫ1 ⅐ 90 min Ϫ1 , P ϭ 0.005). In a second group of subjects (n ϭ 13), acylated ghrelin was similarly suppressed during pregnancy. Circulating octanoate concentrations (3.1 Ϯ 0.5 vs. 4.5 Ϯ 0.6 g/ml, P ϭ 0.029) and cholinesterase activity (705 Ϯ 33 vs. 1,013 Ϯ 56 U/ml, P Ͻ 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. In vitro studies suggest that, in humans, circulating ghrelin is deacylated rapidly, at least in part by the enzyme cholinesterase (also known as pseudocholinesterase or butyrylcholinesterase, EC 3.1.1.8) (9).Both AG and DG could potentially play a physiological role in energy balance. Exogenous administration of AG, but not DG, stimulates GH secretion (35) and has orexigenic effects (41) in humans. AG injection also causes hyperglycemia and a decrease in circulating insulin (2). In addition, in rodents, administration of both AG...

The role of maternal gut hormones in normal pregnancy: fasting plasma active glucagon-like peptide 1 level is a negative predictor of fetal abdomen circumference and maternal weight change

“…In the past, basal acylated ghrelin and PYY 3-36 were found to be increased and decreased respectively only in morbidly obese pregnant women compared with overweight or lean pregnant women (42). Others have reported that acylated ghrelin decreases markedly during pregnancy in mothers with and without gestational diabetes (43). In addition, ghrelin levels have been reported to be low in obesity, hyperinsulinemic, and insulin-resistant states (44,45).…”

Effects of glucose and insulin on acyl ghrelin and desacyl ghrelin, leptin, and adiponectin in pregnant women with diabetes

“…The presence of an acyl chain (octanoate residue) added by the enzyme ghrelin-O-acyl transferase to the serine 3 moiety of ghrelin [1, 2] is required for binding to the GH secretagogue receptor (GHSR), which mediates many of the actions ascribed to ghrelin [3]. Once in the plasma, AG is rapidly deacylated into DG by cholinesterase [4, 5]. …”

“…In humans, we recently characterized ghrelin homeostasis in pregnant women with and without gestational diabetes [5]. We found markedly decreased AG concentrations during pregnancy (the significance of which remains unclear), whereas DG concentrations were similar during pregnancy and after delivery.…”

Gestational diabetes mellitus (GDM) decreases butyrylcholinesterase (BChE) activity and changes its relationship with lipids

“…Pregnancy is associated with physiological changes that include an increase in caloric intake, greater accumulation of fat mass and a progressive increase in insulin resistance (Tham et al , 2009). Towards the end of pregnancy, the insulin resistance approaches that of DM2 patients.…”