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

Metabolomic signatures of low birthweight:: pathways to insulin resistance and oxidative stress
Metabolomic signatures of low birthweight:: pathways to insulin resistance and oxidative stress
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.
1932-6203
Metrustry, Sarah J.
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Karhunen, Ville
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Edwards, M.H.
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Menni, C.
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Geisendorfer, T.
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Huber, A.
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Reichel, C.
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Dennison, Elaine
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Cooper, Cyrus
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Spector, T.
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Jarvelin, M.-R.
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Valdes, A.M.
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Metrustry, Sarah J.
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Karhunen, Ville
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Edwards, M.H.
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Menni, C.
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Geisendorfer, T.
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Huber, A.
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Reichel, C.
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Dennison, Elaine
ee647287-edb4-4392-8361-e59fd505b1d1
Cooper, Cyrus
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Spector, T.
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Jarvelin, M.-R.
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Valdes, A.M.
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Metrustry, Sarah J., Karhunen, Ville, Edwards, M.H., Menni, C., Geisendorfer, T., Huber, A., Reichel, C., Dennison, Elaine, Cooper, Cyrus, Spector, T., Jarvelin, M.-R. and Valdes, A.M. (2018) Metabolomic signatures of low birthweight:: pathways to insulin resistance and oxidative stress. PLoS ONE.

Record type: Article

Abstract

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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Accepted/In Press date: 27 February 2018
e-pub ahead of print date: 22 March 2018

Identifiers

Local EPrints ID: 419146
URI: https://eprints.soton.ac.uk/id/eprint/419146
ISSN: 1932-6203
PURE UUID: 6d9331b8-f7ed-4ead-a38d-d97ffabbb5f1
ORCID for Elaine Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 06 Apr 2018 16:30
Last modified: 10 Dec 2019 01:54

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Contributors

Author: Sarah J. Metrustry
Author: Ville Karhunen
Author: M.H. Edwards
Author: C. Menni
Author: T. Geisendorfer
Author: A. Huber
Author: C. Reichel
Author: Elaine Dennison ORCID iD
Author: Cyrus Cooper ORCID iD
Author: T. Spector
Author: M.-R. Jarvelin
Author: A.M. Valdes

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