Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders
Prenatal alcohol exposure (PAE) causes fetal growth restrictions. A major driver of fetal growth deficits is maternal metabolic disruption; this is under-investigated following PAE. Untargeted metabolomics on the dam and fetus exposed to alcohol (ALC) revealed that the hepatic metabolome of ALC and...
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MDPI AG
2022-03-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/5/1096 |
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| author | Nipun Saini Manjot S. Virdee Kaylee K. Helfrich Sze Ting Cecilia Kwan Sandra M. Mooney Susan M. Smith |
| author_facet | Nipun Saini Manjot S. Virdee Kaylee K. Helfrich Sze Ting Cecilia Kwan Sandra M. Mooney Susan M. Smith |
| author_sort | Nipun Saini |
| collection | DOAJ |
| description | Prenatal alcohol exposure (PAE) causes fetal growth restrictions. A major driver of fetal growth deficits is maternal metabolic disruption; this is under-investigated following PAE. Untargeted metabolomics on the dam and fetus exposed to alcohol (ALC) revealed that the hepatic metabolome of ALC and control (CON) dams were distinct, whereas that of ALC and CON fetuses were similar. Alcohol reduced maternal hepatic glucose content and enriched essential amino acid (AA) catabolites, N-acetylated AA products, urea content, and free fatty acids. These alterations suggest an attempt to minimize the glucose gap by increasing gluconeogenesis using AA and glycerol. In contrast, ALC fetuses had unchanged glucose and AA levels, suggesting an adequate draw of maternal nutrients, despite intensified stress on ALC dams. Maternal metabolites including glycolytic intermediates, AA catabolites, urea, and one-carbon-related metabolites correlated with fetal liver and brain weights, whereas lipid metabolites correlated with fetal body weight, indicating they may be drivers of fetal weight outcomes. Together, these data suggest that ALC alters maternal hepatic metabolic activity to limit glucose availability, thereby switching to alternate energy sources to meet the high-energy demands of pregnancy. Their correlation with fetal phenotypic outcomes indicates the influence of maternal metabolism on fetal growth and development. |
| first_indexed | 2024-03-09T20:25:56Z |
| format | Article |
| id | doaj.art-1e414275a12047c2b3bb16005ce12cf5 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T20:25:56Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-1e414275a12047c2b3bb16005ce12cf52023-11-23T23:34:27ZengMDPI AGNutrients2072-66432022-03-01145109610.3390/nu14051096Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum DisordersNipun Saini0Manjot S. Virdee1Kaylee K. Helfrich2Sze Ting Cecilia Kwan3Sandra M. Mooney4Susan M. Smith5UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USAUNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USAUNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USAUNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USAUNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USAUNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USAPrenatal alcohol exposure (PAE) causes fetal growth restrictions. A major driver of fetal growth deficits is maternal metabolic disruption; this is under-investigated following PAE. Untargeted metabolomics on the dam and fetus exposed to alcohol (ALC) revealed that the hepatic metabolome of ALC and control (CON) dams were distinct, whereas that of ALC and CON fetuses were similar. Alcohol reduced maternal hepatic glucose content and enriched essential amino acid (AA) catabolites, N-acetylated AA products, urea content, and free fatty acids. These alterations suggest an attempt to minimize the glucose gap by increasing gluconeogenesis using AA and glycerol. In contrast, ALC fetuses had unchanged glucose and AA levels, suggesting an adequate draw of maternal nutrients, despite intensified stress on ALC dams. Maternal metabolites including glycolytic intermediates, AA catabolites, urea, and one-carbon-related metabolites correlated with fetal liver and brain weights, whereas lipid metabolites correlated with fetal body weight, indicating they may be drivers of fetal weight outcomes. Together, these data suggest that ALC alters maternal hepatic metabolic activity to limit glucose availability, thereby switching to alternate energy sources to meet the high-energy demands of pregnancy. Their correlation with fetal phenotypic outcomes indicates the influence of maternal metabolism on fetal growth and development.https://www.mdpi.com/2072-6643/14/5/1096pregnancyprenatal alcohol exposurehepatic metabolismuntargeted metabolomicsglucoseamino acids |
| spellingShingle | Nipun Saini Manjot S. Virdee Kaylee K. Helfrich Sze Ting Cecilia Kwan Sandra M. Mooney Susan M. Smith Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders Nutrients pregnancy prenatal alcohol exposure hepatic metabolism untargeted metabolomics glucose amino acids |
| title | Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders |
| title_full | Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders |
| title_fullStr | Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders |
| title_full_unstemmed | Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders |
| title_short | Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders |
| title_sort | untargeted metabolome analysis reveals reductions in maternal hepatic glucose and amino acid content that correlate with fetal organ weights in a mouse model of fetal alcohol spectrum disorders |
| topic | pregnancy prenatal alcohol exposure hepatic metabolism untargeted metabolomics glucose amino acids |
| url | https://www.mdpi.com/2072-6643/14/5/1096 |
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