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Metabolomic Profiles in Childhood and Adolescence Are Associated with Fetal Overnutrition

Fetal overnutrition predisposes offspring to increased metabolic risk. The current study used metabolomics to assess sustained differences in serum metabolites across childhood and adolescence among youth exposed to three typologies of fetal overnutrition: maternal obesity only, gestational diabetes...

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Autores principales: Francis, Ellen C., Kechris, Katerina, Cohen, Catherine C., Michelotti, Gregory, Dabelea, Dana, Perng, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952572/
https://www.ncbi.nlm.nih.gov/pubmed/35323708
http://dx.doi.org/10.3390/metabo12030265
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author Francis, Ellen C.
Kechris, Katerina
Cohen, Catherine C.
Michelotti, Gregory
Dabelea, Dana
Perng, Wei
author_facet Francis, Ellen C.
Kechris, Katerina
Cohen, Catherine C.
Michelotti, Gregory
Dabelea, Dana
Perng, Wei
author_sort Francis, Ellen C.
collection PubMed
description Fetal overnutrition predisposes offspring to increased metabolic risk. The current study used metabolomics to assess sustained differences in serum metabolites across childhood and adolescence among youth exposed to three typologies of fetal overnutrition: maternal obesity only, gestational diabetes mellitus (GDM) only, and obesity + GDM. We included youth exposed in utero to obesity only (BMI ≥ 30; n = 66), GDM only (n = 56), obesity + GDM (n = 25), or unexposed (n = 297), with untargeted metabolomics measured at ages 10 and 16 years. We used linear mixed models to identify metabolites across both time-points associated with exposure to any overnutrition, using a false-discovery-rate correction (FDR) <0.20. These metabolites were included in a principal component analysis (PCA) to generate profiles and assess metabolite profile differences with respect to overnutrition typology (adjusted for prenatal smoking, offspring age, sex, and race/ethnicity). Fetal overnutrition was associated with 52 metabolites. PCA yielded four factors accounting for 17–27% of the variance, depending on age of measurement. We observed differences in three factor patterns with respect to overnutrition typology: sphingomyelin-mannose (8–13% variance), skeletal muscle metabolism (6–10% variance), and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF; 3–4% variance). The sphingomyelin-mannose factor score was higher among offspring exposed to obesity vs. GDM. Exposure to obesity + GDM (vs. GDM or obesity only) was associated with higher skeletal muscle metabolism and CMPF scores. Fetal overnutrition is associated with metabolic changes in the offspring, but differences between typologies of overnutrition account for a small amount of variation in the metabolome, suggesting there is likely greater pathophysiological overlap than difference.
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spelling pubmed-89525722022-03-26 Metabolomic Profiles in Childhood and Adolescence Are Associated with Fetal Overnutrition Francis, Ellen C. Kechris, Katerina Cohen, Catherine C. Michelotti, Gregory Dabelea, Dana Perng, Wei Metabolites Article Fetal overnutrition predisposes offspring to increased metabolic risk. The current study used metabolomics to assess sustained differences in serum metabolites across childhood and adolescence among youth exposed to three typologies of fetal overnutrition: maternal obesity only, gestational diabetes mellitus (GDM) only, and obesity + GDM. We included youth exposed in utero to obesity only (BMI ≥ 30; n = 66), GDM only (n = 56), obesity + GDM (n = 25), or unexposed (n = 297), with untargeted metabolomics measured at ages 10 and 16 years. We used linear mixed models to identify metabolites across both time-points associated with exposure to any overnutrition, using a false-discovery-rate correction (FDR) <0.20. These metabolites were included in a principal component analysis (PCA) to generate profiles and assess metabolite profile differences with respect to overnutrition typology (adjusted for prenatal smoking, offspring age, sex, and race/ethnicity). Fetal overnutrition was associated with 52 metabolites. PCA yielded four factors accounting for 17–27% of the variance, depending on age of measurement. We observed differences in three factor patterns with respect to overnutrition typology: sphingomyelin-mannose (8–13% variance), skeletal muscle metabolism (6–10% variance), and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF; 3–4% variance). The sphingomyelin-mannose factor score was higher among offspring exposed to obesity vs. GDM. Exposure to obesity + GDM (vs. GDM or obesity only) was associated with higher skeletal muscle metabolism and CMPF scores. Fetal overnutrition is associated with metabolic changes in the offspring, but differences between typologies of overnutrition account for a small amount of variation in the metabolome, suggesting there is likely greater pathophysiological overlap than difference. MDPI 2022-03-19 /pmc/articles/PMC8952572/ /pubmed/35323708 http://dx.doi.org/10.3390/metabo12030265 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Francis, Ellen C.
Kechris, Katerina
Cohen, Catherine C.
Michelotti, Gregory
Dabelea, Dana
Perng, Wei
Metabolomic Profiles in Childhood and Adolescence Are Associated with Fetal Overnutrition
title Metabolomic Profiles in Childhood and Adolescence Are Associated with Fetal Overnutrition
title_full Metabolomic Profiles in Childhood and Adolescence Are Associated with Fetal Overnutrition
title_fullStr Metabolomic Profiles in Childhood and Adolescence Are Associated with Fetal Overnutrition
title_full_unstemmed Metabolomic Profiles in Childhood and Adolescence Are Associated with Fetal Overnutrition
title_short Metabolomic Profiles in Childhood and Adolescence Are Associated with Fetal Overnutrition
title_sort metabolomic profiles in childhood and adolescence are associated with fetal overnutrition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952572/
https://www.ncbi.nlm.nih.gov/pubmed/35323708
http://dx.doi.org/10.3390/metabo12030265
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