Abstract
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<0.0001) in KO.
GH and Pck1 mRNA expression increased in WT but not in KO. In P mice, CR markedly lowered glucose
(−2.7 mmol/l; p<0.0001) in WT and caused fatal hypoglycemia in KO, despite similarly
elevated GH in WT and KO mice. KO animals are more prone to hypoglycemia than WT.
GH, which is high in P animals, does not prevent hypoglycemia caused by CR during
pregnancy. Our data suggest a specific role of AG in the regulation of gluconeogenesis
to maintain euglycemia during pregnancy when energy availability is limited.
Key words
ghrelin - ghrelin
O-acyltransferase - pregnancy mice - carbohydrate metabolism - growth hormone
