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

Authors

Habtamu B. Beyene
Kevin Huynh
Tingting Wang
Sudip Paul
Michelle Cinel
Natalie A. Mellett
Gavriel Olshansky
Thomas G. Meikle
Gerald F. Watts
John Blangero, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

7-2024

Abstract

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).

Comments

Copyright © 2024 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Recommended Citation

Beyene, H. B., Huynh, K., Wang, T., Paul, S., Cinel, M., Mellett, N. A., Olshansky, G., Meikle, T. G., Watts, G. F., Hung, J., Hui, J., Beilby, J., Blangero, J., Moses, E. K., Shaw, J. E., Magliano, D. J., Giles, C., & Meikle, P. J. (2024). 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. EBioMedicine, 105, 105187. https://doi.org/10.1016/j.ebiom.2024.105187

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Publication Title

EBioMedicine

DOI

https://doi.org/10.1016/j.ebiom.2024.105187

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics