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BMC Medicine
Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | Obesity | Research article

Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk: a mother-offspring cohort study

Authors: Sartaj Ahmad Mir, Li Chen, Satvika Burugupalli, Bo Burla, Shanshan Ji, Adam Alexander T. Smith, Kothandaraman Narasimhan, Adaikalavan Ramasamy, Karen Mei-Ling Tan, Kevin Huynh, Corey Giles, Ding Mei, Gerard Wong, Fabian Yap, Kok Hian Tan, Fiona Collier, Richard Saffery, Peter Vuillermin, Anne K. Bendt, David Burgner, Anne-Louise Ponsonby, Yung Seng Lee, Yap Seng Chong, Peter D. Gluckman, Johan G. Eriksson, Peter J. Meikle, Markus R. Wenk, Neerja Karnani

Published in: BMC Medicine | Issue 1/2022

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Abstract

Background

Lipids play a vital role in health and disease, but changes to their circulating levels and the link with obesity remain poorly characterized in expecting mothers and their offspring in early childhood.

Methods

LC-MS/MS-based quantitation of 480 lipid species was performed on 2491 plasma samples collected at 4 time points in the mother-offspring Asian cohort GUSTO (Growing Up in Singapore Towards healthy Outcomes). These 4 time points constituted samples collected from mothers at 26–28 weeks of gestation (n=752) and 4–5 years postpartum (n=650), and their offspring at birth (n=751) and 6 years of age (n=338). Linear regression models were used to identify the pregnancy and developmental age-specific variations in the plasma lipidomic profiles, and their association with obesity risk. An independent birth cohort (n=1935), the Barwon Infant Study (BIS), comprising mother-offspring dyads of Caucasian origin was used for validation.

Results

Levels of 36% of the profiled lipids were significantly higher (absolute fold change > 1.5 and Padj < 0.05) in antenatal maternal circulation as compared to the postnatal phase, with phosphatidylethanolamine levels changing the most. Compared to antenatal maternal lipids, cord blood showed lower concentrations of most lipid species (79%) except lysophospholipids and acylcarnitines. Changes in lipid concentrations from birth to 6 years of age were much higher in magnitude (log2FC=−2.10 to 6.25) than the changes observed between a 6-year-old child and an adult (postnatal mother) (log2FC=−0.68 to 1.18). Associations of cord blood lipidomic profiles with birth weight displayed distinct trends compared to the lipidomic profiles associated with child BMI at 6 years. Comparison of the results between the child and adult BMI identified similarities in association with consistent trends (R2=0.75). However, large number of lipids were associated with BMI in adults (67%) compared to the children (29%). Pre-pregnancy BMI was specifically associated with decrease in the levels of phospholipids, sphingomyelin, and several triacylglycerol species in pregnancy.

Conclusions

In summary, our study provides a detailed landscape of the in utero lipid environment provided by the gestating mother to the growing fetus, and the magnitude of changes in plasma lipidomic profiles from birth to early childhood. We identified the effects of adiposity on the circulating lipid levels in pregnant and non-pregnant women as well as offspring at birth and at 6 years of age. Additionally, the pediatric vs maternal overlap of the circulating lipid phenotype of obesity risk provides intergenerational insights and early opportunities to track and intervene the onset of metabolic adversities.

Clinical trial registration

This birth cohort is a prospective observational study, which was registered on 1 July 2010 under the identifier NCT01174875.
Appendix
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Metadata
Title
Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk: a mother-offspring cohort study
Authors
Sartaj Ahmad Mir
Li Chen
Satvika Burugupalli
Bo Burla
Shanshan Ji
Adam Alexander T. Smith
Kothandaraman Narasimhan
Adaikalavan Ramasamy
Karen Mei-Ling Tan
Kevin Huynh
Corey Giles
Ding Mei
Gerard Wong
Fabian Yap
Kok Hian Tan
Fiona Collier
Richard Saffery
Peter Vuillermin
Anne K. Bendt
David Burgner
Anne-Louise Ponsonby
Yung Seng Lee
Yap Seng Chong
Peter D. Gluckman
Johan G. Eriksson
Peter J. Meikle
Markus R. Wenk
Neerja Karnani
Publication date
01-12-2022
Publisher
BioMed Central
Keywords
Obesity
Obesity
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02432-y

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