Effects of altered glucose supply and adiposity on expression of hypothalamic energy balance regulatory genes in late gestation growth restricted ovine fetuses

C L Adam, T Bake, P Findlay, J S Milne, R P Aitken, J M Wallace

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Abstract

Intra-uterine growth restriction (IUGR) predisposes obesity in adulthood. This may be due to altered fetal nutrition causing sustained changes within the developing hypothalamic energy balance regulatory system. Using our established ovine model of IUGR, 130-day singleton fetuses (term=147 days) were obtained from growing adolescent mothers on control dietary intake (C), high intake (H) or H with growth hormone administration during either early (H+early GH) or late gestation (H+late GH) (n=6/group). GH increased maternal glycemia for the duration of treatment. H and H+early GH fetuses showed IUGR compared with C fetuses; body weight was partially restored in H+late GH fetuses, with 40% increased adiposity. In the fetal hypothalamic arcuate nucleus (ARC), cocaine- and amphetamine-regulated transcript mRNA (anorexigenic) was decreased in H fetuses and correlated across all groups with total fetal liver glycogen. Neuropeptide Y, agouti-related peptide (orexigenic) and proopiomelanocortin (anorexigenic) mRNAs were not different between groups. Insulin receptor mRNA in the ARC was increased in H, H+early GH and H+late GH fetuses and correlated negatively with fetal plasma insulin. Leptin receptor mRNA in the ARC correlated positively with fetal plasma leptin concentration and fetal fat content. Therefore, in IUGR fetuses, a key anorexigenic neuropeptide is sensitive to altered glucose supply and the hypothalamic leptin-signaling pathway is altered prenatally by increased adiposity and leptinemia. These changes could impact on postnatal energy balance regulation.
Original languageEnglish
Pages (from-to)775-781
Number of pages7
JournalInternational Journal of Developmental Neuroscience
Volume29
Issue number7
Early online date17 May 2011
DOIs
Publication statusPublished - Nov 2011

Fingerprint

Adiposity
Regulator Genes
Sheep
Fetus
Glucose
Pregnancy
Arcuate Nucleus of Hypothalamus
Growth
Messenger RNA
Leptin
Mothers
Leptin Receptors
Pro-Opiomelanocortin
Liver Glycogen
Neuropeptide Y
Insulin Receptor
Amphetamine
Neuropeptides
Cocaine
Growth Hormone

Keywords

  • intra-uterine growth restriction
  • fetus
  • hypothalamus
  • glucose
  • adiposity
  • neuropeptides
  • leptin receptor

Cite this

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title = "Effects of altered glucose supply and adiposity on expression of hypothalamic energy balance regulatory genes in late gestation growth restricted ovine fetuses",
abstract = "Intra-uterine growth restriction (IUGR) predisposes obesity in adulthood. This may be due to altered fetal nutrition causing sustained changes within the developing hypothalamic energy balance regulatory system. Using our established ovine model of IUGR, 130-day singleton fetuses (term=147 days) were obtained from growing adolescent mothers on control dietary intake (C), high intake (H) or H with growth hormone administration during either early (H+early GH) or late gestation (H+late GH) (n=6/group). GH increased maternal glycemia for the duration of treatment. H and H+early GH fetuses showed IUGR compared with C fetuses; body weight was partially restored in H+late GH fetuses, with 40{\%} increased adiposity. In the fetal hypothalamic arcuate nucleus (ARC), cocaine- and amphetamine-regulated transcript mRNA (anorexigenic) was decreased in H fetuses and correlated across all groups with total fetal liver glycogen. Neuropeptide Y, agouti-related peptide (orexigenic) and proopiomelanocortin (anorexigenic) mRNAs were not different between groups. Insulin receptor mRNA in the ARC was increased in H, H+early GH and H+late GH fetuses and correlated negatively with fetal plasma insulin. Leptin receptor mRNA in the ARC correlated positively with fetal plasma leptin concentration and fetal fat content. Therefore, in IUGR fetuses, a key anorexigenic neuropeptide is sensitive to altered glucose supply and the hypothalamic leptin-signaling pathway is altered prenatally by increased adiposity and leptinemia. These changes could impact on postnatal energy balance regulation.",
keywords = "intra-uterine growth restriction, fetus, hypothalamus, glucose, adiposity, neuropeptides, leptin receptor",
author = "Adam, {C L} and T Bake and P Findlay and Milne, {J S} and Aitken, {R P} and Wallace, {J M}",
note = "Copyright {\circledC} 2011. Published by Elsevier Ltd.",
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T1 - Effects of altered glucose supply and adiposity on expression of hypothalamic energy balance regulatory genes in late gestation growth restricted ovine fetuses

AU - Adam, C L

AU - Bake, T

AU - Findlay, P

AU - Milne, J S

AU - Aitken, R P

AU - Wallace, J M

N1 - Copyright © 2011. Published by Elsevier Ltd.

PY - 2011/11

Y1 - 2011/11

N2 - Intra-uterine growth restriction (IUGR) predisposes obesity in adulthood. This may be due to altered fetal nutrition causing sustained changes within the developing hypothalamic energy balance regulatory system. Using our established ovine model of IUGR, 130-day singleton fetuses (term=147 days) were obtained from growing adolescent mothers on control dietary intake (C), high intake (H) or H with growth hormone administration during either early (H+early GH) or late gestation (H+late GH) (n=6/group). GH increased maternal glycemia for the duration of treatment. H and H+early GH fetuses showed IUGR compared with C fetuses; body weight was partially restored in H+late GH fetuses, with 40% increased adiposity. In the fetal hypothalamic arcuate nucleus (ARC), cocaine- and amphetamine-regulated transcript mRNA (anorexigenic) was decreased in H fetuses and correlated across all groups with total fetal liver glycogen. Neuropeptide Y, agouti-related peptide (orexigenic) and proopiomelanocortin (anorexigenic) mRNAs were not different between groups. Insulin receptor mRNA in the ARC was increased in H, H+early GH and H+late GH fetuses and correlated negatively with fetal plasma insulin. Leptin receptor mRNA in the ARC correlated positively with fetal plasma leptin concentration and fetal fat content. Therefore, in IUGR fetuses, a key anorexigenic neuropeptide is sensitive to altered glucose supply and the hypothalamic leptin-signaling pathway is altered prenatally by increased adiposity and leptinemia. These changes could impact on postnatal energy balance regulation.

AB - Intra-uterine growth restriction (IUGR) predisposes obesity in adulthood. This may be due to altered fetal nutrition causing sustained changes within the developing hypothalamic energy balance regulatory system. Using our established ovine model of IUGR, 130-day singleton fetuses (term=147 days) were obtained from growing adolescent mothers on control dietary intake (C), high intake (H) or H with growth hormone administration during either early (H+early GH) or late gestation (H+late GH) (n=6/group). GH increased maternal glycemia for the duration of treatment. H and H+early GH fetuses showed IUGR compared with C fetuses; body weight was partially restored in H+late GH fetuses, with 40% increased adiposity. In the fetal hypothalamic arcuate nucleus (ARC), cocaine- and amphetamine-regulated transcript mRNA (anorexigenic) was decreased in H fetuses and correlated across all groups with total fetal liver glycogen. Neuropeptide Y, agouti-related peptide (orexigenic) and proopiomelanocortin (anorexigenic) mRNAs were not different between groups. Insulin receptor mRNA in the ARC was increased in H, H+early GH and H+late GH fetuses and correlated negatively with fetal plasma insulin. Leptin receptor mRNA in the ARC correlated positively with fetal plasma leptin concentration and fetal fat content. Therefore, in IUGR fetuses, a key anorexigenic neuropeptide is sensitive to altered glucose supply and the hypothalamic leptin-signaling pathway is altered prenatally by increased adiposity and leptinemia. These changes could impact on postnatal energy balance regulation.

KW - intra-uterine growth restriction

KW - fetus

KW - hypothalamus

KW - glucose

KW - adiposity

KW - neuropeptides

KW - leptin receptor

U2 - 10.1016/j.ijdevneu.2011.05.004

DO - 10.1016/j.ijdevneu.2011.05.004

M3 - Article

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SP - 775

EP - 781

JO - International Journal of Developmental Neuroscience

JF - International Journal of Developmental Neuroscience

SN - 0736-5748

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ER -