Longitudinal Metabolomic Profiling of Amino Acids and Lipids across Healthy Pregnancy

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

Abstract

Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and ultimately, infant health outcomes. However, our understanding of whole body maternal and fetal metabolism during this critical life stage remains incomplete. The objective of this study is to utilize metabolomics to profile longitudinal patterns of fasting maternal metabolites among a cohort of non-diabetic, healthy pregnant women in order to advance our understanding of changes in protein and lipid concentrations across gestation, the biochemical pathways by which they are metabolized and to describe variation in maternal metabolites between ethnic groups. Among 160 pregnant women, amino acids, tricarboxylic acid (TCA) cycle intermediates, keto-bodies and non-esterified fatty acids were detected by liquid chromatography coupled with mass spectrometry, while polar lipids were detected through flow-injected mass spectrometry. The maternal plasma concentration of several essential and non-essential amino acids, long-chain polyunsaturated fatty acids, free carnitine, acetylcarnitine, phosphatidylcholines and sphingomyelins significantly decreased across pregnancy. Concentrations of several TCA intermediates increase as pregnancy progresses, as well as the keto-body β-hydroxybutyrate. Ratios of specific acylcarnitines used as indicators of metabolic pathways suggest a decreased beta-oxidation rate and increased carnitine palmitoyltransferase-1 enzyme activity with advancing gestation. Decreasing amino acid concentrations likely reflects placental uptake and tissue biosynthesis. The absence of any increase in plasma non-esterified fatty acids is unexpected in the catabolic phase of later pregnancy and may reflect enhanced placental fatty acid uptake and utilization for fetal tissue growth. While it appears that energy production through the TCA cycle increases as pregnancy progresses, decreasing patterns of free carnitine and acetylcarnitine as well as increased carnitine palmitoyltransferase-1 rate and β-hydroxybutyrate levels suggest a concomitant upregulation of ketogenesis to ensure sufficient energy supply in the fasting state. Several differences in metabolomic profiles between Hispanic and non-Hispanic women demonstrate phenotypic variations in prenatal metabolism which should be considered in future studies.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Barplot comparing plasma amino acid…
Fig 1. Barplot comparing plasma amino acid concentrations across trimesters among pregnant women.
Median (+ Interquartile range/2) was plotted. * p-value

Fig 2. Barplot comparing plasma non-esterified fatty…

Fig 2. Barplot comparing plasma non-esterified fatty acid concentrations across trimesters among pregnant women.

Median…

Fig 2. Barplot comparing plasma non-esterified fatty acid concentrations across trimesters among pregnant women.
Median (+ Interquartile range/2) was plotted * p-value

Fig 3. Barplot comparing metabolic ratios as…

Fig 3. Barplot comparing metabolic ratios as indicators of β-oxidation (right) and carnitine palmitoyl transferase-1…

Fig 3. Barplot comparing metabolic ratios as indicators of β-oxidation (right) and carnitine palmitoyl transferase-1 activity (left) across trimesters among pregnant women.
Median (+ Interquartile range/2) was plotted * p-value

Fig 4. Barplot comparing plasma concentrations of…

Fig 4. Barplot comparing plasma concentrations of tricarboxylic acid cycle intermediates and keto acids across…

Fig 4. Barplot comparing plasma concentrations of tricarboxylic acid cycle intermediates and keto acids across trimesters among pregnant women.
Median (+ Interquartile range/2) was plotted * p-value
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References
    1. Herrera A. Metabolic alterations in pregnancy and their implications for the availability of substrates for the fetus. Eur J Clin Nutr. 2000; 54: S47–S51. - PubMed
    1. Hadden DR, McLaughlin C. Normal and abnormal maternal metabolism during pregnancy. Sem Neonat Fet Med. 2009; 14: 66–71. - PubMed
    1. Butte NF. Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr. 2000; 71: 1256S–61S. - PubMed
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    1. Iva SK. Metabolic adaptations in pregnancy in lean and obese women—a literature review. Res Obstet Gynecol. 2013; 2: 37–47.
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Fig 2. Barplot comparing plasma non-esterified fatty…
Fig 2. Barplot comparing plasma non-esterified fatty acid concentrations across trimesters among pregnant women.
Median (+ Interquartile range/2) was plotted * p-value

Fig 3. Barplot comparing metabolic ratios as…

Fig 3. Barplot comparing metabolic ratios as indicators of β-oxidation (right) and carnitine palmitoyl transferase-1…

Fig 3. Barplot comparing metabolic ratios as indicators of β-oxidation (right) and carnitine palmitoyl transferase-1 activity (left) across trimesters among pregnant women.
Median (+ Interquartile range/2) was plotted * p-value

Fig 4. Barplot comparing plasma concentrations of…

Fig 4. Barplot comparing plasma concentrations of tricarboxylic acid cycle intermediates and keto acids across…

Fig 4. Barplot comparing plasma concentrations of tricarboxylic acid cycle intermediates and keto acids across trimesters among pregnant women.
Median (+ Interquartile range/2) was plotted * p-value
Similar articles
Cited by
References
    1. Herrera A. Metabolic alterations in pregnancy and their implications for the availability of substrates for the fetus. Eur J Clin Nutr. 2000; 54: S47–S51. - PubMed
    1. Hadden DR, McLaughlin C. Normal and abnormal maternal metabolism during pregnancy. Sem Neonat Fet Med. 2009; 14: 66–71. - PubMed
    1. Butte NF. Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr. 2000; 71: 1256S–61S. - PubMed
    1. Herrera E, Amusquivar E, Lopez-Soldado L, Ortego H. Maternal lipid metabolism and placental lipid transfer. Horm Res. 2006; 65(suppl 3): 59–64. - PubMed
    1. Iva SK. Metabolic adaptations in pregnancy in lean and obese women—a literature review. Res Obstet Gynecol. 2013; 2: 37–47.
Show all 50 references
Publication types
MeSH terms
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

Follow NCBI
Fig 3. Barplot comparing metabolic ratios as…
Fig 3. Barplot comparing metabolic ratios as indicators of β-oxidation (right) and carnitine palmitoyl transferase-1 activity (left) across trimesters among pregnant women.
Median (+ Interquartile range/2) was plotted * p-value

Fig 4. Barplot comparing plasma concentrations of…

Fig 4. Barplot comparing plasma concentrations of tricarboxylic acid cycle intermediates and keto acids across…

Fig 4. Barplot comparing plasma concentrations of tricarboxylic acid cycle intermediates and keto acids across trimesters among pregnant women.
Median (+ Interquartile range/2) was plotted * p-value
Similar articles
Cited by
References
    1. Herrera A. Metabolic alterations in pregnancy and their implications for the availability of substrates for the fetus. Eur J Clin Nutr. 2000; 54: S47–S51. - PubMed
    1. Hadden DR, McLaughlin C. Normal and abnormal maternal metabolism during pregnancy. Sem Neonat Fet Med. 2009; 14: 66–71. - PubMed
    1. Butte NF. Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr. 2000; 71: 1256S–61S. - PubMed
    1. Herrera E, Amusquivar E, Lopez-Soldado L, Ortego H. Maternal lipid metabolism and placental lipid transfer. Horm Res. 2006; 65(suppl 3): 59–64. - PubMed
    1. Iva SK. Metabolic adaptations in pregnancy in lean and obese women—a literature review. Res Obstet Gynecol. 2013; 2: 37–47.
Show all 50 references
Publication types
MeSH terms
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Fig 4. Barplot comparing plasma concentrations of…
Fig 4. Barplot comparing plasma concentrations of tricarboxylic acid cycle intermediates and keto acids across trimesters among pregnant women.
Median (+ Interquartile range/2) was plotted * p-value

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