Development and Validation of a Human Blood Acyl-Specific Lipidomic Profiling Method for Clinical Applications
Notice bibliographique
Résumé
Blood fatty acid levels have been used to determine dietary intakes of omega-3 highly unsaturated fatty acids, but also to examine the link between blood fatty acids, health and disease. However, these lipid analyses are gas chromatography-based and are dependent on derivatization of lipids to fatty acid methyl esters and do not provide information about the fatty acyl parent lipid species. The use of ultra high-performance liquid chromatography combined with tandem mass spectrometry (UHPLC-MS/MS) has the potential to do so. This thesis adapted a lipidomic approach to traditional blood fatty acid profiling to characterize lipids in their naturally-occurring state in human blood. Semi-quantitative methods using UHPLC-MS/MS were developed using a high-resolution Quadrupole-Orbitrap Hybrid Mass Spectrometer (Thermo Q-Exactive), and were validated for the determination of lipids in whole blood. Molecular species were confirmed for over 500 lipids, including phospholipids, sphingolipids, triacylglycerols, cholesteryl esters, free cholesterol and free fatty acids. Over 150 acyl-specific species were confirmed from all lipid classes. Following this, the method was used to validate dried blood spots for lipidomic profiling as this sampling technique offers several advantages, including minimally invasive sample collection, stability, and facilitated handling. Additionally, the UHPLC-MS/MS method was used to examine whole blood lipid remodeling that follows fish oil supplementation. Specifically, the blood lipidomic profiles of samples from a previous intervention trial comprising 20 participants that received eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA) at 150 mg/d, 500 mg/d, and 1000 mg/d over a twelve-week period were determined. Notably, lipidomic profiling of whole blood suggests that three specific lipids (16:0/DHA phosphatidylcholine, 16:0/EPA phosphatidylcholine, and plasmenyl-phosphatidylethanolamine P-16:0/EPA) increase in a dose-dependent manner with increasing doses of EPA+DHA supplementation. Finally, lipidomic analyses of whole blood, plasma, and erythrocytes of individuals that consumed low, intermediate, and high amounts of EPA+DHA were performed. These results support previous observations on the rapid responsiveness of 16:0/DHA phosphatidylcholine and 16:0/EPA phosphatidylcholine to varying levels of EPA+DHA intake. The mechanisms through which lipid remodeling occurs remain to be elucidated. The work presented in this thesis provides the foundation for the use of acyl-specific complex lipids as biomarkers for omega-3 highly unsaturated fatty acid status and the lipidomic profiling method developed may be extrapolated for the characterization of acyl-specific lipids in other biological matrices.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,005 | 0,005 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».