title: Ghrelin, Ghrelin O-Acyltransferase, and Carbohydrate Metabolism During Pregnancy in Calorie-Restricted Mice.
abstract: Acylation of ghrelin is mediated by ghrelinO-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 andPck1expression. 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 andPck1mRNA 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.
authors.affiliation: Child & Family Research Institute, Vancouver, BC, Canada.
authors.forename: Arjun
authors.initials: A
authors.lastname: Trivedi
authors.affiliation: Child & Family Research Institute, Vancouver, BC, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Babic
authors.affiliation: MicroBiome Therapeutics, New Orleans, LA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Heiman
authors.affiliation: Child & Family Research Institute, Vancouver, BC, Canada.
authors.forename: William T
authors.initials: WT
authors.lastname: Gibson
authors.affiliation: Child & Family Research Institute, Vancouver, BC, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Chanoine
mesh_terms: D000215:Acylation / Q000235:genetics; D000217:Acyltransferases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D031204:Caloric Restriction; D050260:Carbohydrate Metabolism / Q000235:genetics / Q000502:physiology*; D005260:Female; D054439:Ghrelin / Q000378:metabolism / Q000502:physiology*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy
chemical_list: D054439:Ghrelin; D008565:Membrane Proteins; D000217:Acyltransferases; C526983:Mboat4 protein, mouse