Submitted on October 23, 2008
Revised on February 9, 2009
Accepted on February 16, 2009
Acylated ghrelin concentrations are markedly decreased during pregnancy in mothers with and without gestational diabetes: relationship with cholinesterase
Elaine Tham1, Jianhua Liu2, Sheila Innis1, David Thompson3, Bruce D. Gaylinn4, Roberto Bogarin5, Alon Haim5, Michael O. Thorner2, and Jean-Pierre Chanoine5*
1 University of British Columbia
2 University of Virginia Health System
3 Vancouver General Hospital
4 University of Virginia School of Medicine
5 British Columbia's Children's Hospital
* To whom correspondence should be addressed. E-mail: jchanoine{at}cw.bc.ca.
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 during the test meal). In postpartum subjects, the percent of total ghrelin that is acylated was 4-5 times higher than previously observed using single antibody assays. During pregnancy, acylated ghrelin concentrations (mean+/-SE) were lower compared to the postpartum period throughout the meal (AUC 1.2+/-0.2 vs 10.2+/-1.9 ng/ml*90min, P<0.001). In the postpartum, acylated ghrelin and GH 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*90min, 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 1013+/-56 U/ml, P<0.001) were lower during pregnancy compared to 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.
