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
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals and Diets
2.2. Data Analysis and Statistical Analysis
3. Results
3.1. Litter Characteristics
3.2. Metabolite Profiles Distinctly Separate ALC and CON Dams but Not Their Fetuses
3.3. Amino Acid Catabolites Are Enriched in Alcohol-Exposed Maternal and Fetal Liver
3.4. Maternal Metabolite Profile Is Consistent with the Known Impact of Alcohol on Hepatic Metabolism
3.5. Maternal Hepatic Metabolites Are Predictive of Fetal Phenotypic Outcomes
3.6. Fetal Hepatic Metabolites Predict Fetal Brain Weight but Not Fetal Body and Liver Weight
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Top Pathways | Total Compounds | Hits | Raw p | FDR | Metabolites Identified |
---|---|---|---|---|---|
Purine metabolism | 66 | 6 | 4.01 × 10−10 | 1.80 × 10−8 | Xanthine, urate, allantoin, guanosine, sulfate, urea |
Pentose phosphate pathway | 22 | 6 | 8.11 × 10−10 | 1.83 × 10−8 | Glucose 6-phosphate, sedoheptulose 7-phosphate, fructose 6-phosphate, 6-phosphogluconate, gluconic acid, glycerate |
Pyrimidine metabolism | 39 | 4 | 2.21 × 10−8 | 3.31 × 10−7 | 3-ureidopropionate, cytidine, CMP, thymine |
Nicotinate and nicotinamide metabolism | 15 | 3 | 4.40 × 10−7 | 3.96 × 10−6 | Quinolinate, nicotinate D-ribonucleoside, nicotinamide-beta-riboside |
Glycolysis/gluconeogenesis | 26 | 3 | 3.12 × 10−6 | 2.00 × 10−5 | Thiamin diphosphate, fructose 6-phosphate, glucose 6-phosphate |
Fatty acid biosynthesis | 47 | 3 | 7.81 × 10−6 | 4.39 × 10−5 | Tetradecanoic acid, dodecanoic acid, decanoic acid |
Metabolite Name | FC (ALC/CON) | p-Value | q-Value |
---|---|---|---|
N-Acetylated Amino-acid Products | |||
N-Acetylalanine | 0.82 | 0.0142 | 0.0536 |
N-Acetylasparagine | 1.49 | 0.0188 | 0.0653 |
N-Acetylaspartate (NAA) | 0.93 | 0.7304 | 0.8229 |
N-Acetylglutamate | 1.92 | 0.0056 | 0.0264 |
N-Acetylglutamine | 1.24 | 0.3401 | 0.4994 |
N-Acetylglycine | 1.35 | 0.7304 | 0.8229 |
N-Acetylserine | 0.93 | 0.2224 | 0.3773 |
N-Acetylthreonine | 1.29 | 0.0106 | 0.0423 |
N-Acetylhistidine | 1.49 | 0.0106 | 0.0423 |
N-Acetylleucine | 1.02 | 0.9314 | 0.9512 |
N-Acetylvaline | 0.98 | 0.8633 | 0.9140 |
N-Acetylcysteine | 0.99 | 0.7962 | 0.8632 |
N-Acetylmethionine | 0.85 | 0.0503 | 0.1334 |
N-Acetyltaurine | 1.40 | 0.0028 | 0.0154 |
N-Acetylphenylalanine | 1.15 | 0.1135 | 0.2443 |
Essential Amino-Acid Catabolites | |||
2-hydroxy-3-methylvalerate | 1.43 | 0.0315 | 0.0961 |
3-hydroxyisobutyrate | 1.39 | 0.0625 | 0.1582 |
4-methyl-2-oxopentanoate | 0.53 | 0.2868 | 0.4505 |
α-hydroxyisovalerate | 1.60 | 0.0001 | 0.0022 |
β-hydroxyisovalerate | 0.98 | 0.8633 | 0.9140 |
β-hydroxyisovaleroylcarnitine | 1.10 | 0.0400 | 0.1109 |
Isovalerylcarnitine (C5) | 1.40 | 0.1903 | 0.3429 |
Isovalerylglycine | 1.46 | 0.2581 | 0.4063 |
Pipecolate | 1.67 | 0.0000 | 0.0014 |
Picolinate | 1.96 | 0.0002 | 0.0032 |
Fatty-Acyl Carnitines | |||
Carnitine | 0.94 | 0.5457 | 0.6749 |
Adipoylcarnitine (C6-DC) | 0.36 | 0.0062 | 0.0287 |
3-Methyladipoylcarnitine (C7-DC) | 0.66 | 0.0000 | 0.0014 |
(R)-3-hydroxybutyrylcarnitine | 0.53 | 0.0106 | 0.0423 |
(S)-3-hydroxybutyrylcarnitine | 0.51 | 0.0078 | 0.0338 |
3-hydroxyoleoylcarnitine | 1.98 | 0.0079 | 0.0343 |
Acetylcarnitine (C2) | 0.87 | 0.2581 | 0.4063 |
Propionylcarnitine (C3) | 0.67 | 0.1575 | 0.3089 |
Malonylcarnitine | 0.65 | 0.0171 | 0.0637 |
Isobutyrylcarnitine (C4) | 0.69 | 0.0625 | 0.1582 |
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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
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 StyleSaini, Nipun, Manjot S. Virdee, Kaylee K. Helfrich, Sze Ting Cecilia 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
APA StyleSaini, N., Virdee, M. S., Helfrich, K. K., Kwan, S. T. C., Mooney, S. M., & Smith, S. M. (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(5), 1096. https://doi.org/10.3390/nu14051096