Development and validation of a plasmalogen score as an independent modifiable marker of metabolic health : population based observational studies and a placebo-controlled cross-over study

Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..

BACKGROUND: Decreased levels of circulating ethanolamine plasmalogens [PE(P)], and a concurrent increase in phosphatidylethanolamine (PE) are consistently reported in various cardiometabolic conditions. Here we devised, a plasmalogen score (Pls Score) that mirrors a metabolic signal that encompasses the levels of PE(P) and PE and captures the natural variation in circulating plasmalogens and perturbations in their metabolism associated with disease, diet, and lifestyle.

METHODS: We utilised, plasma lipidomes from the Australian Obesity, Diabetes and Lifestyle study (AusDiab; n = 10,339, 55% women) a nationwide cohort, to devise the Pls Score and validated this in the Busselton Health Study (BHS; n = 4,492, 56% women, serum lipidome) and in a placebo-controlled crossover trial involving Shark Liver Oil (SLO) supplementation (n = 10, 100% men). We examined the association of the Pls Score with cardiometabolic risk factors, type 2 diabetes mellitus (T2DM), cardiovascular disease and all-cause mortality (over 17 years).

FINDINGS: In a model, adjusted for age, sex and BMI, individuals in the top quintile of the Pls Score (Q5) relative to Q1 had an OR of 0.31 (95% CI 0.21-0.43), 0.39 (95% CI 0.25-0.61) and 0.42 (95% CI 0.30-0.57) for prevalent T2DM, incident T2DM and prevalent cardiovascular disease respectively, and a 34% lower mortality risk (HR = 0.66; 95% CI 0.56-0.78). Significant associations between diet and lifestyle habits and Pls Score exist and these were validated through dietary supplementation of SLO that resulted in a marked change in the Pls Score.

INTERPRETATION: The Pls Score as a measure that captures the natural variation in circulating plasmalogens, was not only inversely related to cardiometabolic risk and all-cause mortality but also associate with diet and lifestyle. Our results support the potential utility of the Pls Score as a biomarker for metabolic health and its responsiveness to dietary interventions. Further research is warranted to explore the underlying mechanisms and optimise the practical implementation of the Pls Score in clinical and population settings.

FUNDING: National Health and Medical Research Council (NHMRC grant 233200), National Health and Medical Research Council of Australia (Project grant APP1101320), Health Promotion Foundation of Western Australia, and National Health and Medical Research Council of Australia Senior Research Fellowship (#1042095).

Media Type:

Electronic Article

Year of Publication:

2024

Publication:

2024

Contained In:

To Main Record - volume:105

Contained In:

EBioMedicine - 105(2024) vom: 01. Juli, Seite 105187

Language:

English

Contributors:

Beyene, Habtamu B [Author]
Huynh, Kevin [Author]
Wang, Tingting [Author]
Paul, Sudip [Author]
Cinel, Michelle [Author]
Mellett, Natalie A [Author]
Olshansky, Gavriel [Author]
Meikle, Thomas G [Author]
Watts, Gerald F [Author]
Hung, Joseph [Author]
Hui, Jennie [Author]
Beilby, John [Author]
Blangero, John [Author]
Moses, Eric K [Author]
Shaw, Jonathan E [Author]
Magliano, Dianna J [Author]
Giles, Corey [Author]
Meikle, Peter J [Author]

Links:

Volltext

Keywords:

Biomarkers
Diet
Journal Article
Lifestyle intervention
Metabolic health
Observational Study
Phosphatidylethanolamines
Plasmalogens
Pls Score

Notes:

Date Completed 12.07.2024

Date Revised 31.08.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ebiom.2024.105187

funding:

Supporting institution / Project title:

PPN (Catalogue-ID):

NLM37349985X