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Article

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

1
UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA
2
Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Robert Colin Carter
Nutrients 2022, 14(5), 1096; https://doi.org/10.3390/nu14051096
Received: 10 February 2022 / Revised: 2 March 2022 / Accepted: 3 March 2022 / Published: 5 March 2022
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. View Full-Text
Keywords: pregnancy; prenatal alcohol exposure; hepatic metabolism; untargeted metabolomics; glucose; amino acids; maternal–fetal metabolism; fetal weight; gluconeogenesis pregnancy; prenatal alcohol exposure; hepatic metabolism; untargeted metabolomics; glucose; amino acids; maternal–fetal metabolism; fetal weight; gluconeogenesis
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MDPI and ACS Style

Saini, N.; Virdee, M.S.; Helfrich, K.K.; Kwan, S.T.C.; Mooney, S.M.; Smith, S.M. 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 2022, 14, 1096. https://doi.org/10.3390/nu14051096

AMA Style

Saini N, Virdee MS, Helfrich KK, Kwan STC, Mooney SM, Smith SM. 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. 2022; 14(5):1096. https://doi.org/10.3390/nu14051096

Chicago/Turabian Style

Saini, Nipun, Manjot S. Virdee, Kaylee K. Helfrich, Sze T.C. Kwan, Sandra M. Mooney, and Susan M. Smith. 2022. "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 14, no. 5: 1096. https://doi.org/10.3390/nu14051096

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