University of Oulu

Metrustry SJ, Karhunen V, Edwards MH, Menni C, Geisendorfer T, et al. (2018) Metabolomic signatures of low birthweight: Pathways to insulin resistance and oxidative stress. PLOS ONE 13(3): e0194316.

Metabolomic signatures of low birthweight : pathways to insulin resistance and oxidative stress

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Author: Metrustry, Sarah Jane1; Karhunen, Ville2,3; Edwards, Mark H.4;
Organizations: 1Department of Twin Research and Genetic Epidemiology, Kings College London, St Thomas’ Hospital
2Center for Life Course Health Research, Faculty of Medicine, University of Oulu
3Oulu University Hospital, Unit of Primary Care
4MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital
5Department of Twin Research and Genetic Epidemiology, Kings College London
6St Thomas’ Hospital
7Seibersdorf Labor GmbH
8Victoria University
9NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford
10NIHR Nutrition Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton General Hospital
11Kings College London, St Thomas’ Hospital
12Department of Epidemiology and Biostatistics, MRC–PHE Centre for Environment & Health, School of Public Health, Imperial College London
13Biocenter Oulu, University of Oulu
14University of Nottingham
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
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Language: English
Published: Public Library of Science, 2018
Publish Date: 2018-05-17


Several studies suggest that low birthweight resulting from restricted intrauterine growth can leave a metabolic footprint which may persist into adulthood. To investigate this, we performed metabolomic profiling on 5036 female twins, aged 18–80, with weight at birth information available from the TwinsUK cohort and performed independent replication in two additional cohorts. Out of 422 compounds tested, 25 metabolites associated with birthweight in these twins, replicated in 1951 men and women from the Hertfordshire Cohort Study (HCS, aged 66) and in 2391 men and women from the North Finland Birth 1986 cohort (NFBC, aged 16). We found distinct heterogeneity between sexes and, after adjusting for multiple tests and heterogeneity, two metabolites were reproducible overall (propionylcarnitine and 3-4-hydroxyphenyllactate). Testing women only, we found other metabolites associated with lower birthweight from the meta-analysis of the three cohorts (2-hydroxy-butyric acid and γ-glutamylleucine). Higher levels of all these metabolites can be linked to insulin resistance, oxidative stress or a dysfunction of energy metabolism, suggesting that low birthweight in both twins and singletons are having an impact on these pathways in adulthood.

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Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 13
Issue: 3
Article number: e0194316
DOI: 10.1371/journal.pone.0194316
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: TwinsUK: The study was supported by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR)- funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. This work was funded by the H2020 grant 'Health and Environment-wide Associations based on Large population Surveys (HEALS)' - Grant Agreement Number 603946. The Hertfordshire Cohort Study was supported by the Medical Research Council (MRC) of Great Britain; Arthritis Research UK; and the International Osteoporosis Foundation. The work herein was also supported by the NIHR Nutrition BRC, University of Southampton and the Oxford NIHR Musculoskeletal BRU, University of Oxford. NFBC1986 was supported by the Academy of Finland, University Hospital Oulu, Biocenter, University of Oulu, Finland, the European Commission (Framework 5 award, EURO-BLCS, QLG1-CT-2000-01643, Framework 7 EurHEALTHAgeing 277849), and the Medical Research Council, UK.
EU Grant Number: (277849) EURHEALTHAGEING - European ResearcH on DevElopmentAL, BirtH and Genetic Determinants of Ageing
Copyright information: © 2018 Metrustry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.