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Horm Metab Res 2017; 49(01): 64-72
DOI: 10.1055/s-0042-116117
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

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

Arjun Trivedi
1   Child & Family Research Institute, Vancouver, BC, Canada
2   University of British Columbia, Vancouver, BC, Canada
3   British Columbia Children’s Hospital, Vancouver, BC, Canada
,
Sandra Babic
1   Child & Family Research Institute, Vancouver, BC, Canada
,
Mark Heiman
4   MicroBiome Therapeutics, New Orleans, LA, USA
,
William T. Gibson
1   Child & Family Research Institute, Vancouver, BC, Canada
2   University of British Columbia, Vancouver, BC, Canada
3   British Columbia Children’s Hospital, Vancouver, BC, Canada
,
Jean-Pierre Chanoine
1   Child & Family Research Institute, Vancouver, BC, Canada
2   University of British Columbia, Vancouver, BC, Canada
3   British Columbia Children’s Hospital, Vancouver, BC, Canada
› Author Affiliations
Further Information

Publication History

received 05 January 2016

accepted 25 July 2016

Publication Date:
04 October 2016 (online)

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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

Supporting Information

 

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