Clinical lipidomics reveals high individuality and sex specificity of circulatory lipid signatures: a prospective healthy population study

Abstract Lipid metabolism and circulatory lipid levels are tightly associated with the (cardio)metabolic health. Consequently, MS-based lipidomics has emerged as a powerful phenotyping tool in epidemiological, human population, and in clinical intervention studies. However, ensuring high-throughput...

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Main Authors: Jessica Medina, Nicolas Goss, Gonçalo dos Santos Correia, Rebecca Borreggine, Tony Teav, Zoltan Kutalik, Pedro Marques Vidal, Hector Gallart-Ayala, Julijana Ivanisevic
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Journal of Lipid Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0022227525000409
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author Jessica Medina
Nicolas Goss
Gonçalo dos Santos Correia
Rebecca Borreggine
Tony Teav
Zoltan Kutalik
Pedro Marques Vidal
Hector Gallart-Ayala
Julijana Ivanisevic
author_facet Jessica Medina
Nicolas Goss
Gonçalo dos Santos Correia
Rebecca Borreggine
Tony Teav
Zoltan Kutalik
Pedro Marques Vidal
Hector Gallart-Ayala
Julijana Ivanisevic
author_sort Jessica Medina
collection DOAJ
description Abstract Lipid metabolism and circulatory lipid levels are tightly associated with the (cardio)metabolic health. Consequently, MS-based lipidomics has emerged as a powerful phenotyping tool in epidemiological, human population, and in clinical intervention studies. However, ensuring high-throughput and reproducible measurement of a wide panel of circulatory lipid species in large-scale studies poses a significant challenge. Here, we applied a recently developed quantitative LC-MS/MS lipidomics approach to a subset of 1,086 fasted plasma samples belonging to apparently healthy participants from prospective Lausanne population study. This high-coverage and high-throughput hydrophilic interaction liquid chromatography–based methodology allowed for the robust measurement of 782 circulatory lipid species spanning 22 lipid classes and six orders of magnitude-wide concentration range. This was achieved by combining semiautomated sample preparation using a stable isotope dilution approach and the alternate analysis of National Institute of Standards and Technology plasma reference material, as a quality control. Based on National Institute of Standards and Technology quality control analysis, median between-batch reproducibility was 8.5%, over the course of analysis of 13 independent batches comprising 1,086 samples collected from 364 individuals at three time points. Importantly, the biological variability, per lipid species, was significantly higher than the batch-to-batch analytical variability. Furthermore, the significantly lower between-subject (than within-subject) variability and unsupervised sample clustering demonstrated the high individuality and sex specificity of circulatory lipidome. The most prominent sex differences were reported for sphingomyelins and ether-linked phospholipids present in significantly higher concentrations in female plasma. The high individuality and sex specificity of circulatory lipidome constitute important pre-requisites for the application of lipidomics in next-generation metabolic health monitoring.
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spelling doaj-art-ca80ec2151d24723ad72fc45ecf6d76b2025-08-20T03:10:24ZengElsevierJournal of Lipid Research0022-22752025-05-0166510078010.1016/j.jlr.2025.100780Clinical lipidomics reveals high individuality and sex specificity of circulatory lipid signatures: a prospective healthy population studyJessica Medina0Nicolas Goss1Gonçalo dos Santos Correia2Rebecca Borreggine3Tony Teav4Zoltan Kutalik5Pedro Marques Vidal6Hector Gallart-Ayala7Julijana Ivanisevic8Metabolomics and Lipidomics and Lipidomics Platform, Faculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandMetabolomics and Lipidomics and Lipidomics Platform, Faculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandInstitute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; March of Dimes Prematurity Research Centre at Imperial College London, London, UKMetabolomics and Lipidomics and Lipidomics Platform, Faculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandMetabolomics and Lipidomics and Lipidomics Platform, Faculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandDepartment of Computational Biology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandDepartment of Medicine, Internal Medicine, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, SwitzerlandMetabolomics and Lipidomics and Lipidomics Platform, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland; For correspondence: Hector Gallart-Ayala; Julijana IvanisevicMetabolomics and Lipidomics and Lipidomics Platform, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland; For correspondence: Hector Gallart-Ayala; Julijana IvanisevicAbstract Lipid metabolism and circulatory lipid levels are tightly associated with the (cardio)metabolic health. Consequently, MS-based lipidomics has emerged as a powerful phenotyping tool in epidemiological, human population, and in clinical intervention studies. However, ensuring high-throughput and reproducible measurement of a wide panel of circulatory lipid species in large-scale studies poses a significant challenge. Here, we applied a recently developed quantitative LC-MS/MS lipidomics approach to a subset of 1,086 fasted plasma samples belonging to apparently healthy participants from prospective Lausanne population study. This high-coverage and high-throughput hydrophilic interaction liquid chromatography–based methodology allowed for the robust measurement of 782 circulatory lipid species spanning 22 lipid classes and six orders of magnitude-wide concentration range. This was achieved by combining semiautomated sample preparation using a stable isotope dilution approach and the alternate analysis of National Institute of Standards and Technology plasma reference material, as a quality control. Based on National Institute of Standards and Technology quality control analysis, median between-batch reproducibility was 8.5%, over the course of analysis of 13 independent batches comprising 1,086 samples collected from 364 individuals at three time points. Importantly, the biological variability, per lipid species, was significantly higher than the batch-to-batch analytical variability. Furthermore, the significantly lower between-subject (than within-subject) variability and unsupervised sample clustering demonstrated the high individuality and sex specificity of circulatory lipidome. The most prominent sex differences were reported for sphingomyelins and ether-linked phospholipids present in significantly higher concentrations in female plasma. The high individuality and sex specificity of circulatory lipidome constitute important pre-requisites for the application of lipidomics in next-generation metabolic health monitoring.http://www.sciencedirect.com/science/article/pii/S0022227525000409circulatory lipidsclinical lipidomicsHILIC-MS/MSpersonalized signaturesprospective healthy populationsex differences
spellingShingle Jessica Medina
Nicolas Goss
Gonçalo dos Santos Correia
Rebecca Borreggine
Tony Teav
Zoltan Kutalik
Pedro Marques Vidal
Hector Gallart-Ayala
Julijana Ivanisevic
Clinical lipidomics reveals high individuality and sex specificity of circulatory lipid signatures: a prospective healthy population study
Journal of Lipid Research
circulatory lipids
clinical lipidomics
HILIC-MS/MS
personalized signatures
prospective healthy population
sex differences
title Clinical lipidomics reveals high individuality and sex specificity of circulatory lipid signatures: a prospective healthy population study
title_full Clinical lipidomics reveals high individuality and sex specificity of circulatory lipid signatures: a prospective healthy population study
title_fullStr Clinical lipidomics reveals high individuality and sex specificity of circulatory lipid signatures: a prospective healthy population study
title_full_unstemmed Clinical lipidomics reveals high individuality and sex specificity of circulatory lipid signatures: a prospective healthy population study
title_short Clinical lipidomics reveals high individuality and sex specificity of circulatory lipid signatures: a prospective healthy population study
title_sort clinical lipidomics reveals high individuality and sex specificity of circulatory lipid signatures a prospective healthy population study
topic circulatory lipids
clinical lipidomics
HILIC-MS/MS
personalized signatures
prospective healthy population
sex differences
url http://www.sciencedirect.com/science/article/pii/S0022227525000409
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