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Identification of Phenotypic Lipidomic Signatures in Response to Long Chain n‐3 Polyunsaturated Fatty Acid Supplementation in Humans

Title: Identification of Phenotypic Lipidomic Signatures in Response to Long Chain n‐3 Polyunsaturated Fatty Acid Supplementation in Humans
Authors: Picklo, Matthew; Vallée Marcotte, Bastien; Bukowski, Michael; de Toro‐Martín, Juan; Rust, Bret M.; Guénard, Frédéric; Vohl, Marie‐Claude
Source: Journal of the American Heart Association ; volume 10, issue 3 ; ISSN 2047-9980
Publisher Information: Ovid Technologies (Wolters Kluwer Health)
Publication Year: 2021
Description: Background Supplementation with long chain n‐3 polyunsaturated fatty acids is used to reduce total circulating triacylglycerol (TAG) concentrations. However, in about 30% of people, supplementation with long chain n‐3 polyunsaturated fatty acids does not result in decreased plasma TAG. Lipidomic analysis may provide insight into this inter‐individual variability. Methods Lipidomic analyses using targeted, mass spectrometry were performed on plasma samples obtained from a clinical study in which participants were supplemented with 3 g/day of long chain n‐3 in the form of fish oil capsules over a 6‐week period. TAG species and cholesteryl esters (CE) were quantified for 130 participants pre‐ and post‐supplementation. Participants were segregated into 3 potential responder phenotypes: (1) positive responder (R pos ; TAG decrease), (2) non‐responder (R non ; lacking TAG change), and (3) negative responder (R neg ; TAG increase) representing 67%, 18%, and 15% of the study participants, respectively. Separation of the 3 phenotypes was attributed to differential responses in TAG with 50 to 54 carbons with 1 to 4 desaturations. Elevated TAG with higher carbon number and desaturation were common to all phenotypes following supplementation. Using the TAG responder phenotype for grouping, decreases in total CE and specific CE occurred in the R pos phenotype versus the R neg phenotype with intermediate responses in the R non phenotype. CE 20:5, containing eicosapentaenoic acid (20:5n‐3), was elevated in all phenotypes. A classifier combining lipidomic and genomic features was built to discriminate triacylglycerol response phenotypes and reached a high predictive performance with a balanced accuracy of 75%. Conclusions These data identify lipidomic signatures, TAG and CE, associated with long chain n‐3 response p henotypes and identify a novel phenotype based upon CE changes. Registration URL: https://www.ClinicalTrials.gov ; Unique Identifier: NCT01343342.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1161/jaha.120.018126
DOI: 10.1161/JAHA.120.018126
Availability: https://doi.org/10.1161/jaha.120.018126; https://www.ahajournals.org/doi/full/10.1161/JAHA.120.018126
Accession Number: edsbas.95B886D5
Database: BASE