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FASEB J. 2017 Apr;31(4):1698-1708. doi: 10.1096/fj.201601032R. Epub 2017 Jan 12.

Gestational disruptions in metabolic rhythmicity of the liver, muscle, and placenta affect fetal size.

Author information

1
Division of Women's Health, Guy's Campus, King's College London, London, United Kingdom.
2
Institute of Reproductive and Developmental Biology, Surgery and Cancer, Hammersmith Hospital, Imperial College London, London, United Kingdom.
3
Women's Health Research Centre, Surgery and Cancer, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom.
4
Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; and.
5
Harris Birthright Centre for Fetal Medicine, King's College London, London, United Kingdom.
6
Division of Women's Health, Guy's Campus, King's College London, London, United Kingdom; catherine.williamson@kcl.ac.uk.

Abstract

Maternal metabolic adaptations are essential for successful pregnancy outcomes. We investigated how metabolic gestational processes are coordinated, whether there is a functional link with internal clocks, and whether disruptions are related to metabolic abnormalities in pregnancy, by studying day/night metabolic pathways in murine models and samples from pregnant women with normally grown and large-for-gestational age infants. In early mouse pregnancy, expression of hepatic lipogenic genes was up-regulated and uncoupled from the hepatic clock. In late mouse pregnancy, rhythmicity of energy metabolism-related genes in the muscle followed the patterns of internal clock genes in this tissue, and coincided with enhanced lipid transporter expression in the fetoplacental unit. Diurnal triglyceride patterns were disrupted in human placentas from pregnancies with large-for-gestational age infants and this overlapped with an increase in BMAL1 expression. Metabolic adaptations in early pregnancy are uncoupled from the circadian clock, whereas in late pregnancy, energy availability is mediated by coordinated muscle-placenta metabolic adjustments linked to internal clocks. Placental triglyceride oscillations in the third trimester of human pregnancy are lost in large-for-gestational age infants and may be regulated by BMAL1. In summary, disruptions in metabolic and circadian rhythmicity are associated with increased fetal size, with implications for the pathogenesis of macrosomia.-Papacleovoulou, G., Nikolova, V., Oduwole, O., Chambers, J., Vazquez-Lopez, M., Jansen, E., Nicolaides, K., Parker, M., Williamson, C. Gestational disruptions in metabolic rhythmicity of the liver, muscle, and placenta affect fetal size.

KEYWORDS:

circadian clock; macrosomia; metabolism; pregnancy; triglycerides

PMID:
28082353
PMCID:
PMC5566176
DOI:
10.1096/fj.201601032R
[Indexed for MEDLINE]
Free PMC Article

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