Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sample Processing and Preparation
2.2. Liquid Chromatography–High-Resolution Mass Spectrometry (LC–HRMS) Metabolite Analyses
2.3. Biostatistical Analysis
2.4. Over-Representation Analysis
2.5. Pathway Analyses
3. Results
3.1. Nervous and Non-Nervous Tissues Display Similar Metabolite Profiles
3.2. Post-Weaning Diets Affect the Metabolite Profiles of both the Liver and Hypothalamus
3.3. Post-Weaning Diet Has a Major Impact on Metabolite Abundance in the Liver
3.4. Maternal Diet Affects the Liver Abundance of Two Metabolites
4. Discussion
4.1. The Liver, Hypothalamus and Olfactory Bulb Metabolomes Were Principally Affected by Chronic HFD
4.2. The Maternal Environment Has a Persistent Effect on Metabolites in the Liver
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Decreased under HFD | Increased under HFD | |
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Liver (LI) | 1,5-Anhydro-d-sorbitol; l-Saccharopine; Indoxyl-sulfate; Imidazolelactic-acid; Methylhippurate; 3-Methylhistidine; Methionine; 2-Deoxyribose-5-phosphate; UMP; Inosine-5-monophosphate; GMP; 4-Guanidinobutyric-acid; 3-AMP/5-AMP; 4-Hydroxy-3-methoxyphenylglycol-sulfate; 3-Methylcrotonyl-glycine/N-Tiglylglycine; Guanine; l-Alanyl-l-proline; d-Glucosamine-6-phosphate; Glycerol-3-phosphate; Hydroxyphenylpyruvic-acid; Cytidine; ortho-Methylhippuric-acid/meta-Methylhippuric-acid/para-Methylhippuric-acid/Phenylacetylglycine; d-Fructose-1-phosphate/d-Fructose-6-phosphate/d-Mannose-6-phosphate/Galactose-1-phosphate/Glucose-1-phosphate/Glucose-6-PO4/Mannose-1-phosphate; Caprylolyglycine; UDP; Nervonic-acid; N-Acetyl-l-methionine; N-Isobutyrylglycine; 2-Oxobutyric-acid; N-Glycolylneuraminic-acid; 5-AMP/dGMP; Phosphonoacetic-acid; Guanosine-5-diphospho-d-mannose/Guanosine-5-diphosphoglucose; dGMP; Serine; Orotic-acid; Hexanoyl-glycine/N-Acetyl-d-allo-isoleucine/N-Acetyl-l-leucine; N-Acetyl-d-penicillamine/N-Acetyl-l-Methionine; Hexanoyl-glycine; Phosphoserine; Deoxyinosine; Uridine; Sebacic-acid; Guanosine-5-diphospho-l-fucose; 5-Aminolevulinic-acid/cis-4-hydroxy-d-proline/trans-3-Hydroxy-l-proline/trans-4-hydroxy-l-proline; Purine; Myristic-acid; N-Acetylneuraminic-acid; d-Pyroglutamic-acid; Muramic-acid; Leu-Pro; Pyrrole-2-carboxylic-acid; D-Arabinose | 3-Hydroxybutyric-acid; N-N-Dimethylglycine; Betaine; NAD; Taurine; 13-S-Hydroxyoctadeca-9Z-11E-dienoic-acid; Argininosuccinic-acid; 1-Methyladenosine; S-Adenosyl-homocysteine; Cyclic-ADP-ribose; dl-alpha-Hydroxystearic-acid; gamma-Linolenic-acid; β-Alanine; d-Threitol; Asparagine; 3-Ureidopropionic-acid; Quinolinic-acid; l-Glutamic-acid; N-Methyl-d-aspartic-acid; Stachydrine; l-Cysteinesulfinic-acid; l-Kynurenine; Propionylcarnitine; ADP; 2-O-Methylinosine; Riboflavin; Pyridoxamine-5-phosphate; Sphinganine; 3-Hydroxy-2-methyl-butanoic-acid/3-Hydroxypentanoic-acid; Perillic-acid; l-Cysteic-acid; d-Sphingosine; 2-Aminopyridine-3-carboxylic-acid; Phosphoenolpyruvic-acid; 2-O-Methylguanosine; Fumaric-acid/Maleic-acid; 3-Hydroxypicolinic-acid; Uracil; Xanthosine; Diglycolic-acid/Malic-acid; d-Mannitol-1-phosphate; Prostaglandin-A1; Carnitine; Prostaglandin-E1; Indolelactic-acid; 5-Aminoimidazole-4-carboxamide-1b-d-ribofuranoside; Nicotinic-acid; 2-Hydroxyhexadecanoic-acid; Xanthine; N6-N6-N6-Trimethyl-l-lysine; Arachidic-acid; Cytidine-5-diphosphocholine; 4-Pyridoxic-acid; d-Glyceric-acid; Aldosterone |
Hypothalamus (HYP) | 1,5-Anhydro-d-sorbitol; l-Saccharopine; 3-Methylhistidine | 3-Hydroxybutyric-acid; Argininosuccinic-acid; Pantothenic-acid; Tyrosine; dl-Tryptophan; Phenylalanine; Arginine; Tartaric-acid; Valine; Asparagine; Gly-Pro/Pro-Gly; 3-Aminosalicylic-acid; Leu-Pro |
Whole olfactory bulb (WOB) | 1,5-Anhydro-d-sorbitol; l-Saccharopine; cis-5,8,11,14,17-Eicosapentaenoic-acid; cis-8,11,14-Eicosatrienoic-acid; Lysine; trans-4-hydroxy-l-proline; l-Homoserine/Threonine | 3-Hydroxybutyric-acid; gamma-Linolenic-acid; Pantothenic-acid; 3-Aminosalicylic-acid |
Pathways | Total Compounds | Hits | FDR | Impact | Metabolites |
---|---|---|---|---|---|
D-Glutamine and D-glutamate metabolism | 5 | 1 | 0.00002 | 100% | L-Glutamic acid ↑ |
Ubiquinone and other terpenoid-quinone biosynthesis | 3 | 1 | 0.00644 | 100% | 4-Hydroxyphenylpyruvic acid ↓ |
Taurine and hypotaurine metabolism | 8 | 3 | 0.00002 | 71% | Cysteic acid ↑; 3-Sulfinoalanine ↑; Taurine ↑ |
Beta-alanine metabolism | 17 | 3 | 0.00001 | 67% | Beta-alanine ↑; Ureidopropionic acid ↑; Uracil ↑ |
Methane metabolism | 9 | 1 | 0.02049 | 40% | L-Serine ↓ |
Glycine, serine and threonine metabolism | 31 | 5 | 0.00001 | 36% | Dimethylglycine ↑; Phosphoserine ↓ |
Purine metabolism | 68 | 8 | 0.00001 | 28% | Xanthine ↑; AICAR ↑; Inosinic acid ↓; Deoxyinosine ↓; Xanthosine ↑; Guanosine monophosphate ↓; Guanine ↓; 2′-Deoxyguanosine 5′-monophosphate ↓ |
Pyrimidine metabolism | 41 | 8 | 0.00001 | 28% | Uridine 5′-diphosphate ↓; Uridine 5′-monophosphate ↓; Uridine ↑; Ureidopropionic acid ↑; Cytidine ↑; Orotic acid ↑; Uracil ↑; Beta-Alanine ↑ |
Alanine, aspartate and glutamate metabolism | 24 | 4 | 0.00001 | 28% | Argininosuccinic acid ↑; L-Glutamic acid ↑; L-Asparagine ↓; Glucosamine 6-phosphate ↓ |
Nicotinate and nicotinamide metabolism | 13 | 3 | 0.00001 | 21% | Quinolinic acid ↑; NAD ↑; Nicotinic acid ↑ |
Cysteine and methionine metabolism | 27 | 6 | 0.00001 | 20% | L-Serine ↓; L-Methionine ↑; S-Adenosylhomocysteine ↑; Cysteic acid ↑; 3-Sulfinoalanine ↑; 2-Ketobutyric acid ↓ |
Sphingolipid metabolism | 21 | 3 | 0.00005 | 20% | Sphinganine ↑; L-Serine ↓; Sphingosine ↑ |
Glycerolipid metabolism | 18 | 2 | 0.00019 | 13% | Glycerol 3-phosphate ↓; Glyceric acid ↑ |
Glycerophospholipid metabolism | 30 | 2 | 0.00012 | 13% | Citicoline ↑; Glycerol 3-phosphate ↓ |
Aminoacyl-tRNA biosynthesis | 69 | 4 | 0.00038 | 13% | L-Asparagine ↓; L-Serine ↓; L-Methionine ↑; L-Glutamic acid ↑ |
Arginine and proline metabolism | 44 | 3 | 0.00001 | 12% | Argininosuccinic acid ↑; L-Glutamic acid ↑; 4-Guanidinobutanoic acid ↓ |
Tryptophan metabolism | 40 | 1 | 0.00056 | 11% | L-Kynurenine ↓ |
Glycolysis or gluconeogenesis | 26 | 1 | 0.00032 | 10% | Phosphoenolpyruvic acid ↑ |
Amino sugar and nucleotide sugar metabolism | 37 | 3 | 0.00020 | 8% | Glucosamine 6-phosphate ↓; GDP-L-fucose ↓; N-Glycolylneuraminic acid ↓ |
Tyrosine metabolism | 44 | 1 | 0.00645 | 7% | 4-Hydroxyphenylpyruvic acid ↓ |
Pentose phosphate pathway | 19 | 1 | 0.00002 | 7% | Deoxyribose 5-phosphate ↓ |
Glyoxylate and dicarboxylate metabolism | 18 | 1 | 0.00032 | 6% | Glyceric acid ↑ |
Glutathione metabolism | 26 | 1 | 0.00002 | 6% | L-Glutamic acid ↑ |
Vitamin B6 metabolism | 9 | 2 | 0.00002 | 5% | Pyridoxamine 5′-phosphate ↑; 4-Pyridoxic acid ↑ |
Pantothenate and CoA biosynthesis | 15 | 3 | 0.00001 | 4% | Ureidopropionic acid ↑; Beta-Alanine ↑; Uracil ↑ |
Primary bile acid biosynthesis | 46 | 1 | 0.00002 | 3% | Taurine ↑ |
Lysine degradation | 23 | 2 | 0.00001 | 1% | N6,N6,N6-Trimethyl-L-lysine ↑; Saccharopine ↓ |
Histidine metabolism | 15 | 2 | 0.00001 | 0% | L-Glutamic acid ↑; 1-Methylhistidine ↓ |
Biosynthesis of unsaturated fatty acids | 42 | 3 | 0.00001 | 0% | Nervonic acid ↓; Arachidic acid ↑; Gamma-Linolenic acid ↑ |
Butanoate metabolism | 22 | 1 | 0.00002 | 0% | L-Glutamic acid ↑ |
Porphyrin and chlorophyll metabolism | 27 | 1 | 0.00002 | 0% | L-Glutamic acid ↑ |
Nitrogen metabolism | 9 | 1 | 0.00002 | 0% | L-Glutamic acid ↑ |
Propanoate metabolism | 20 | 2 | 0.00003 | 0% | Beta-Alanine ↑; 2-Ketobutyric acid ↓ |
Linoleic acid metabolism | 6 | 1 | 0.00003 | 0% | 13S-hydroxyoctadecadienoic acid ↑ |
Limonene and pinene degradation | 8 | 1 | 0.00011 | 0% | Perillic acid ↑ |
Riboflavin metabolism | 11 | 1 | 0.00012 | 0% | Riboflavin ↑ |
Citrate cycle (TCA cycle) | 20 | 1 | 0.00032 | 0% | Phosphoenolpyruvic acid ↑ |
Pyruvate metabolism | 23 | 1 | 0.00032 | 0% | Phosphoenolpyruvic acid ↑ |
Lysine biosynthesis | 4 | 1 | 0.00466 | 0% | Saccharopine ↓ |
Phenylalanine, tyrosine and tryptophan biosynthesis | 4 | 1 | 0.00645 | 0% | 4-Hydroxyphenylpyruvic acid ↓ |
Cyanoamino acid metabolism | 6 | 1 | 0.02049 | 0% | L-Serine ↓ |
Pathways | Total Compounds | Hits | FDR | Impact | Metabolites |
---|---|---|---|---|---|
Hypothalamus (KEGG and SMPDB databases retrieved the same results) | |||||
Aspartate metabolism | 34 | 3 | 0.00818 | 35% | L-Asparagine ↑, Argininosuccinic acid ↑, L-Arginine ↑ |
Arginine and proline metabolism | 48 | 2 | 0.00586 | 24% | Argininosuccinic acid ↑, L-Arginine ↑ |
Urea cycle | 23 | 2 | 0.00586 | 22% | Argininosuccinic acid ↑, L-Arginine ↑ |
Phenylalanine and tyrosine metabolism | 25 | 2 | 0.01921 | 12% | L-Phenylalanine ↑, L-Tyrosine ↑ |
Pantothenate and CoA biosynthesis | 19 | 1 | 0.00586 | 7% | Pantothenic acid ↑ |
Ammonia recycling | 25 | 1 | 0.03670 | 3% | L-Asparagine ↑ |
Lysine degradation | 20 | 1 | 0.01921 | 3% | Saccharopine ↓ |
Beta-alanine metabolism | 26 | 2 | 0.00586 | 0% | 3-Methylhistidine ↑, Pantothenic acid ↑ |
Valine, leucine and isoleucine degradation | 51 | 1 | 0.02030 | 0% | L-Valine ↑ |
Catecholamine biosynthesis | 14 | 1 | 0.03065 | 0% | L-Tyrosine ↑ |
Tyrosine metabolism | 55 | 1 | 0.03065 | 0% | L-Tyrosine ↑ |
Whole olfactory bulb (KEGG database) | |||||
Arginine and proline metabolism | 44 | 1 | 0.00233 | 4% | Hydroxyproline ↓ |
Pantothenate and CoA biosynthesis | 15 | 1 | 0.00430 | 2% | Pantothenic acid ↑ |
Lysine degradation | 23 | 2 | 0.00015 | 1% | L-Lysine ↓; Saccharopine ↓ |
Biosynthesis of unsaturated fatty acids | 42 | 3 | 0.00015 | 0% | 8,11,14-Eicosatrienoic acid ↓; Gamma-linolenic acid ↑; Eicosapentaenoic acid ↓ |
Lysine biosynthesis | 4 | 2 | 0.00015 | 0% | L-Lysine ↓; Saccharopine ↓ |
Biotin metabolism | 5 | 1 | 0.00430 | 0% | L-Lysine ↓ |
Aminoacyl-tRNA biosynthesis | 69 | 1 | 0.00430 | 0% | L-Lysine ↓ |
Whole olfactory bulb (SMPDB database) | |||||
Alpha linolenic acid and linoleic acid metabolism | 17 | 3 | 0.00032 | 26% | Eicosapentaenoic acid ↓; 8,11,14-Eicosatrienoic acid ↓; Gamma-Linolenic acid ↑ |
Lysine degradation | 20 | 2 | 0.18397 | 3% | L-Lysine ↓; Saccharopine ↓ |
Biotin metabolism | 7 | 1 | 0.72255 | 0% | L-Lysine ↓ |
Carnitine synthesis | 16 | 1 | 0.72255 | 0% | L-Lysine ↓ |
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Safi-Stibler, S.; Thévenot, E.A.; Jouneau, L.; Jouin, M.; Seyer, A.; Jammes, H.; Rousseau-Ralliard, D.; Baly, C.; Gabory, A. Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes. Nutrients 2020, 12, 1572. https://doi.org/10.3390/nu12061572
Safi-Stibler S, Thévenot EA, Jouneau L, Jouin M, Seyer A, Jammes H, Rousseau-Ralliard D, Baly C, Gabory A. Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes. Nutrients. 2020; 12(6):1572. https://doi.org/10.3390/nu12061572
Chicago/Turabian StyleSafi-Stibler, Sofiane, Etienne A. Thévenot, Luc Jouneau, Mélanie Jouin, Alexandre Seyer, Hélène Jammes, Delphine Rousseau-Ralliard, Christine Baly, and Anne Gabory. 2020. "Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes" Nutrients 12, no. 6: 1572. https://doi.org/10.3390/nu12061572