Maternal Metabolomic Profile and Fetal Programming of Offspring Adiposity: Identification of Potentially Protective Lipid Metabolites

Hellmuth, Christian; Lindsay, Karen L.; Uhl, Olaf; Buß, Claudia; Wadhwa, Pathik D.; Koletzko, Berthold; Entringer, Sonja

doi:10.1002/mnfr.201700889

Cited by 29 publications

(18 citation statements)

References 42 publications

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“…In general, by comparing the metabolite- and methylation-driven analyses we could observe that: i) phosphatidylcholine metabolites, particularly plasmalogens, have been identified in both analyses. Maternal plasmalogens, that are able to cross the placenta, have been recently associated with newborn body composition [ 42 ]. However, most previous studies identified lysoPCs rather than PCs as dominant cord blood metabolites related to birthweight [ 15 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism

et al. 2020

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Background Birthweight reflects in utero exposures and later health evolution. Despite existing studies employing high-dimensional molecular measurements, the understanding of underlying mechanisms of birthweight remains limited. Methods To investigate the systems biology of birthweight, we cross-sectionally integrated the methylome, the transcriptome, the metabolome and a set of inflammatory proteins measured in cord blood samples, collected from four birth-cohorts ( n = 489). We focused on two sets of 68 metabolites and 903 CpGs previously related to birthweight and investigated the correlation structures existing between these two sets and all other omic features via bipartite Pearson correlations. Results This dataset revealed that the set of metabolome and methylome signatures of birthweight have seven signals in common, including three metabolites [PC(34:2), plasmalogen PC(36:4)/PC(O-36:5), and a compound with m/z of 781.0545], two CpGs (on the DHCR24 and SC4MOL gene), and two proteins (periostin and CCL22). CCL22, a macrophage-derived chemokine has not been previously identified in relation to birthweight. Since the results of the omics integration indicated the central role of cholesterol metabolism, we explored the association of cholesterol levels in cord blood with birthweight in the ENVIR ON AGE cohort ( n = 1097), finding that higher birthweight was associated with increased high-density lipoprotein cholesterol and that high-density lipoprotein cholesterol was lower in small versus large for gestational age newborns. Conclusions Our data suggests that an integration of different omic-layers in addition to single omics studies is a useful approach to generate new hypotheses regarding biological mechanisms. CCL22 and cholesterol metabolism in cord blood play a mechanistic role in birthweight.

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Section: Discussionmentioning

confidence: 99%

A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism

et al. 2020

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“…This might be explained by the large timespan between the measurements. Also, previous research has indicated that metabolite concentrations are highly influenced by nutritional factors, physical activity and the gut microbiome (Hellmuth et al 2019;Lau et al 2018;Palmnas et al 2018;Pedersen et al 2016;Wang et al 2011). Differences in these factors between mothers and their children and over time might explain the weak correlations between different time points.…”

Section: Interpretation Of Main Findingsmentioning

confidence: 99%

A population-based resource for intergenerational metabolomics analyses in pregnant women and their children: the Generation R Study

et al. 2020

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Introduction Adverse exposures in early life may predispose children to cardio-metabolic disease in later life. Metabolomics may serve as a valuable tool to disentangle the metabolic adaptations and mechanisms that potentially underlie these associations. Objectives To describe the acquisition, processing and structure of the metabolomics data available in a population-based prospective cohort from early pregnancy onwards and to examine the relationships between metabolite profiles of pregnant women and their children at birth and in childhood. Methods In a subset of 994 mothers-child pairs from a prospective population-based cohort study among pregnant women and their children from Rotterdam, the Netherlands, we used LC-MS/MS to determine concentrations of amino acids, nonesterified fatty acids, phospholipids and carnitines in blood serum collected in early pregnancy, at birth (cord blood), and at child's age 10 years. Results Concentrations of diacyl-phosphatidylcholines, acyl-alkyl-phosphatidylcholines, alkyl-lysophosphatidylcholines and sphingomyelines were the highest in early pregnancy, concentrations of amino acids and non-esterified fatty acids were the highest at birth and concentrations of alkyl-lysophosphatidylcholines, free carnitine and acyl-carnitines were the highest at age 10 years. Correlations of individual metabolites between pregnant women and their children at birth and at the age of 10 years were low (range between r = − 0.10 and r = 0.35). Conclusion Our results suggest that unique metabolic profiles are present among pregnant women, newborns and school aged children, with limited intergenerational correlations between metabolite profiles. These data will form a valuable resource to address the early metabolic origins of cardio-metabolic disease. Keywords Metabolomics • Amino acids • Fatty acids • Phospholipids • Carnitines • Birth cohort Abbreviations AA Amino acids AAA Aromatic amino acids APCI Atmospheric pressure chemical ionization BCAA Branched-chain amino acids Carn Carnitines Carn.a Acyl-carnitines Berthold Koletzko and Romy Gaillard have contributed equally.

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“…Metabolomics analyses have been applied to identify trimester-specific maternal metabolites associated with infant BW and adiposity 13 – 17 , accounting for maternal characteristics such as pre-pregnancy BMI 14 . Maternal metabolite levels, placental transfer, and interaction with other metabolites, such as inhibition by competition or metabolite-induced changes in placental transport activity, can all affect the relative levels of the umbilical cord blood (CB) metabolome.…”

Section: Introductionmentioning

confidence: 99%

Maternal lipid levels across pregnancy impact the umbilical cord blood lipidome and infant birth weight

LaBarre

Puttabyatappa

Song

et al. 2020

Sci Rep

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Major alterations in metabolism occur during pregnancy enabling the mother to provide adequate nutrients to support infant development, affecting birth weight (BW) and potentially long-term risk of obesity and cardiometabolic disease. We classified dynamic changes in the maternal lipidome during pregnancy and identified lipids associated with Fenton BW z-score and the umbilical cord blood (CB) lipidome. Lipidomics was performed on first trimester maternal plasma (M1), delivery maternal plasma (M3), and CB plasma in 106 mother-infant dyads. Shifts in the maternal and CB lipidome were consistent with the selective transport of long-chain polyunsaturated fatty acids (PUFA) as well as lysophosphatidylcholine (LysoPC) and lysophosphatidylethanolamine (LysoPE) species into CB. Partial correlation networks demonstrated fluctuations in correlations between lipid groups at M1, M3, and CB, signifying differences in lipid metabolism. Using linear models, LysoPC and LysoPE groups in CB were positively associated with BW. M1 PUFA containing triglycerides (TG) and phospholipids were correlated with CB LysoPC and LysoPE species and total CB polyunsaturated TGs. These results indicate that early gestational maternal lipid levels influence the CB lipidome and its relationship with BW, suggesting an opportunity to modulate maternal diet and improve long-term offspring cardiometabolic health.

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Maternal Metabolomic Profile and Fetal Programming of Offspring Adiposity: Identification of Potentially Protective Lipid Metabolites

Cited by 29 publications

References 42 publications

A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism

A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism

A population-based resource for intergenerational metabolomics analyses in pregnant women and their children: the Generation R Study

Maternal lipid levels across pregnancy impact the umbilical cord blood lipidome and infant birth weight

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