Plasma Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes: a multi-platform population-based study

Yasir Abozaid; Ibrahim Ayada; Laurens van Kleef; Neil J Goulding; Jessica Williams-Nguyen; Robert Kaplan; Robert de Knegt; Lynne E. Wagenknecht; Nicholette D. Palmer; Nicholas John  Timpson; Jill M. Norris; Yii-Der Ida Chen; M. Arfan Ikram; Willem Pieter Brouwer; Mohsen Ghanbari

doi:10.1016/j.gastha.2024.09.006

Plasma Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes: a multi-platform population-based study

Yasir Abozaid^*, Ibrahim Ayada, Laurens van Kleef, Neil J Goulding, Jessica Williams-Nguyen, Robert Kaplan, Robert de Knegt, Lynne E. Wagenknecht, Nicholette D. Palmer, Nicholas John Timpson, Jill M. Norris, Yii-Der Ida Chen, M. Arfan Ikram, Willem Pieter Brouwer, Mohsen Ghanbari^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

3 Citations (Scopus)

Abstract

Background & Aims:
Steatotic liver disease (SLD) is the most common chronic liver disease strongly associated with metabolic dysfunction, but its pathogenesis remains incompletely understood. Exploring circulating metabolites may help in elucidating underlying mechanisms and identifying new biomarkers for SLD.

Methods:
We examined cross-sectionally the association between plasma metabolites and SLD as well as liver enzymes using data from four population-based cohort studies (Rotterdam study, ALSPAC, IRASFS, and SOL). Metabolites were assessed in the Nightingale platform (n=225 metabolites) by NMR spectroscopy and in the Metabolon platform (n=991 metabolites) by UHPLC-mass spectrometry. Serum levels of liver enzymes (ALT, AST, and GGT) were measured and SLD was diagnosed by ultrasound or CT-scan. Logistic and linear regression models were performed per cohort and meta-analyzed. A false discovery rate (-FDR) < 0.05 was considered as significant threshold.

Results:
Several metabolites were significantly associated with SLD and liver enzymes, of which 21 metabolites were associated with both traits. The most significant associations were observed with phenylalanine, triglycerides in (HDL, IDL, and small-LDL), fatty acid (FA) ratios of (18:2 linoleic acid-to-total FA, omega 6 FA-to-total FA, and polyunsaturated FA-to-total FA) from the Nightingale and glutamate and sphingomyelin from the Metabolon platform. Other associated metabolites were mainly involved in lipid, amino acid, carbohydrates, and peptide metabolism.

Conclusions:
Our study indicates a landscape of circulating metabolites associated with SLD. The identified metabolites may contribute to a better understanding of the metabolic pathways underlying SLD and hold promising for potential biomarkers in early diagnosis and monitoring of the disease.

Original language	English
Article number	100551
Number of pages	14
Journal	Gastro Hep Advances
Volume	4
Issue number	2
Early online date	12 Sept 2024
DOIs	https://doi.org/10.1016/j.gastha.2024.09.006
Publication status	Published - 10 Jan 2025

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute.

Keywords

ALSPAC
Metabolomics
Steatotic Liver Disease
Liver enzymes
general population

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Abozaid, Y., Ayada, I., van Kleef, L., Goulding, N. J., Williams-Nguyen, J., Kaplan, R., de Knegt, R., Wagenknecht, L. E., Palmer, N. D., Timpson, N. J., Norris, J. M., Ida Chen, Y.-D., Ikram, M. A., Brouwer, W. P., & Ghanbari, M. (2025). Plasma Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes: a multi-platform population-based study. Gastro Hep Advances, 4(2), Article 100551. https://doi.org/10.1016/j.gastha.2024.09.006

@article{536bfa13b8624d83b83510da61c50d0c,

title = "Plasma Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes: a multi-platform population-based study",

abstract = "Background \& Aims: Steatotic liver disease (SLD) is the most common chronic liver disease strongly associated with metabolic dysfunction, but its pathogenesis remains incompletely understood. Exploring circulating metabolites may help in elucidating underlying mechanisms and identifying new biomarkers for SLD. Methods: We examined cross-sectionally the association between plasma metabolites and SLD as well as liver enzymes using data from four population-based cohort studies (Rotterdam study, ALSPAC, IRASFS, and SOL). Metabolites were assessed in the Nightingale platform (n=225 metabolites) by NMR spectroscopy and in the Metabolon platform (n=991 metabolites) by UHPLC-mass spectrometry. Serum levels of liver enzymes (ALT, AST, and GGT) were measured and SLD was diagnosed by ultrasound or CT-scan. Logistic and linear regression models were performed per cohort and meta-analyzed. A false discovery rate (-FDR) < 0.05 was considered as significant threshold. Results: Several metabolites were significantly associated with SLD and liver enzymes, of which 21 metabolites were associated with both traits. The most significant associations were observed with phenylalanine, triglycerides in (HDL, IDL, and small-LDL), fatty acid (FA) ratios of (18:2 linoleic acid-to-total FA, omega 6 FA-to-total FA, and polyunsaturated FA-to-total FA) from the Nightingale and glutamate and sphingomyelin from the Metabolon platform. Other associated metabolites were mainly involved in lipid, amino acid, carbohydrates, and peptide metabolism. Conclusions: Our study indicates a landscape of circulating metabolites associated with SLD. The identified metabolites may contribute to a better understanding of the metabolic pathways underlying SLD and hold promising for potential biomarkers in early diagnosis and monitoring of the disease.",

keywords = "ALSPAC, Metabolomics, Steatotic Liver Disease, Liver enzymes, general population",

author = "Yasir Abozaid and Ibrahim Ayada and \{van Kleef\}, Laurens and Goulding, \{Neil J\} and Jessica Williams-Nguyen and Robert Kaplan and \{de Knegt\}, Robert and Wagenknecht, \{Lynne E.\} and Palmer, \{Nicholette D.\} and Timpson, \{Nicholas John\} and Norris, \{Jill M.\} and \{Ida Chen\}, Yii-Der and Ikram, \{M. Arfan\} and Brouwer, \{Willem Pieter\} and Mohsen Ghanbari",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute.",

year = "2025",

month = jan,

day = "10",

doi = "10.1016/j.gastha.2024.09.006",

language = "English",

volume = "4",

journal = "Gastro Hep Advances",

issn = "2772-5723",

publisher = "Elsevier",

number = "2",

}

Abozaid, Y, Ayada, I, van Kleef, L, Goulding, NJ, Williams-Nguyen, J, Kaplan, R, de Knegt, R, Wagenknecht, LE, Palmer, ND, Timpson, NJ, Norris, JM, Ida Chen, Y-D, Ikram, MA, Brouwer, WP & Ghanbari, M 2025, 'Plasma Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes: a multi-platform population-based study', Gastro Hep Advances, vol. 4, no. 2, 100551. https://doi.org/10.1016/j.gastha.2024.09.006

TY - JOUR

T1 - Plasma Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes

T2 - a multi-platform population-based study

AU - Abozaid, Yasir

AU - Ayada, Ibrahim

AU - van Kleef, Laurens

AU - Goulding, Neil J

AU - Williams-Nguyen, Jessica

AU - Kaplan, Robert

AU - de Knegt, Robert

AU - Wagenknecht, Lynne E.

AU - Palmer, Nicholette D.

AU - Timpson, Nicholas John

AU - Norris, Jill M.

AU - Ida Chen, Yii-Der

AU - Ikram, M. Arfan

AU - Brouwer, Willem Pieter

AU - Ghanbari, Mohsen

PY - 2025/1/10

Y1 - 2025/1/10

N2 - Background & Aims: Steatotic liver disease (SLD) is the most common chronic liver disease strongly associated with metabolic dysfunction, but its pathogenesis remains incompletely understood. Exploring circulating metabolites may help in elucidating underlying mechanisms and identifying new biomarkers for SLD. Methods: We examined cross-sectionally the association between plasma metabolites and SLD as well as liver enzymes using data from four population-based cohort studies (Rotterdam study, ALSPAC, IRASFS, and SOL). Metabolites were assessed in the Nightingale platform (n=225 metabolites) by NMR spectroscopy and in the Metabolon platform (n=991 metabolites) by UHPLC-mass spectrometry. Serum levels of liver enzymes (ALT, AST, and GGT) were measured and SLD was diagnosed by ultrasound or CT-scan. Logistic and linear regression models were performed per cohort and meta-analyzed. A false discovery rate (-FDR) < 0.05 was considered as significant threshold. Results: Several metabolites were significantly associated with SLD and liver enzymes, of which 21 metabolites were associated with both traits. The most significant associations were observed with phenylalanine, triglycerides in (HDL, IDL, and small-LDL), fatty acid (FA) ratios of (18:2 linoleic acid-to-total FA, omega 6 FA-to-total FA, and polyunsaturated FA-to-total FA) from the Nightingale and glutamate and sphingomyelin from the Metabolon platform. Other associated metabolites were mainly involved in lipid, amino acid, carbohydrates, and peptide metabolism. Conclusions: Our study indicates a landscape of circulating metabolites associated with SLD. The identified metabolites may contribute to a better understanding of the metabolic pathways underlying SLD and hold promising for potential biomarkers in early diagnosis and monitoring of the disease.

AB - Background & Aims: Steatotic liver disease (SLD) is the most common chronic liver disease strongly associated with metabolic dysfunction, but its pathogenesis remains incompletely understood. Exploring circulating metabolites may help in elucidating underlying mechanisms and identifying new biomarkers for SLD. Methods: We examined cross-sectionally the association between plasma metabolites and SLD as well as liver enzymes using data from four population-based cohort studies (Rotterdam study, ALSPAC, IRASFS, and SOL). Metabolites were assessed in the Nightingale platform (n=225 metabolites) by NMR spectroscopy and in the Metabolon platform (n=991 metabolites) by UHPLC-mass spectrometry. Serum levels of liver enzymes (ALT, AST, and GGT) were measured and SLD was diagnosed by ultrasound or CT-scan. Logistic and linear regression models were performed per cohort and meta-analyzed. A false discovery rate (-FDR) < 0.05 was considered as significant threshold. Results: Several metabolites were significantly associated with SLD and liver enzymes, of which 21 metabolites were associated with both traits. The most significant associations were observed with phenylalanine, triglycerides in (HDL, IDL, and small-LDL), fatty acid (FA) ratios of (18:2 linoleic acid-to-total FA, omega 6 FA-to-total FA, and polyunsaturated FA-to-total FA) from the Nightingale and glutamate and sphingomyelin from the Metabolon platform. Other associated metabolites were mainly involved in lipid, amino acid, carbohydrates, and peptide metabolism. Conclusions: Our study indicates a landscape of circulating metabolites associated with SLD. The identified metabolites may contribute to a better understanding of the metabolic pathways underlying SLD and hold promising for potential biomarkers in early diagnosis and monitoring of the disease.

KW - ALSPAC

KW - Metabolomics

KW - Steatotic Liver Disease

KW - Liver enzymes

KW - general population

U2 - 10.1016/j.gastha.2024.09.006

DO - 10.1016/j.gastha.2024.09.006

M3 - Article (Academic Journal)

C2 - 39877862

SN - 2772-5723

VL - 4

JO - Gastro Hep Advances

JF - Gastro Hep Advances

IS - 2

M1 - 100551

ER -

Plasma Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes: a multi-platform population-based study

Abstract

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Keywords

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