Ghrelin, Ghrelin O-Acyltransferase, and Carbohydrate Metabolism During Pregnancy in Calorie-Restricted Mice

Acylation of ghrelin is mediated by ghrelin O- acyltansferase (GOAT). Exogenous acylated ghrelin (AG) stimulates growth hormone (GH) and food intake. In non-pregnant (NP) animals, the GOAT-ghrelin-GH axis prevents hypoglycemia caused by caloric restriction (CR). In humans, maternal malnutrition challenges glucose metabolism, which is a key determinant of fetal health. To clarify the role of AG and GH, we compared effects of CR on the GOAT-ghrelin-GH axis in pregnant (P) and NP mice. C57BL/6 wild type (WT) and GOAT knock-out (KO) P and NP mice were freely fed (FF) or subjected to 50% CR for one week. CR was started in P mice on Day 10.5 after conception. We measured body composition, blood glucose, plasma ghrelin and GH, stomach, hypothalamus and pituitary GOAT and ghrelin expression, and liver glycogen content and Pck1 expression. GOAT and AG were undetectable in KO. In NP mice, CR did not affect blood glucose (−1.3 mmol/l, p>0.05) in WT but was lowered (−1.8 mmol/l, p Pck1 mRNA expression increased in WT but not in KO. In P mice, CR markedly lowered glucose (−2.7 mmol/l; p