Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study

Ian J. Neeland; Fang Zhu; Goncalo Graca; Anastasios Lymperopoulos; Gianluca Iacobellis; Ali Farzaneh; Daniel Bos; Mohsen Ghanbari; Jeffrey J. Goldberger; Maryam Kavousi; Philip Greenland

doi:10.1161/JAHA.124.039750

Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study

Ian J. Neeland
, Fang Zhu
, Goncalo Graca
, Anastasios Lymperopoulos
, Gianluca Iacobellis
, Ali Farzaneh
, Daniel Bos
, Mohsen Ghanbari
, Jeffrey J. Goldberger
, Maryam Kavousi
, Philip Greenland

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

BACKGROUND: Excess epicardial adipose tissue (EAT) has been associated with cardiovascular diseases such as atrial fibrillation, coronary artery disease, and heart failure. The metabolomic signature of EAT is not well studied. METHODS: Untargeted 1H nuclear magnetic resonance metabolomics profiling of serum was performed (1- dimensional nuclear magnetic resonance, Carr–Purcell–Meiboom–Gill Echo Train Acquisition, lipidomics) and EAT was measured with computed tomography in MESA (Multi- Ethnic Study of Atherosclerosis; N=3936) and the Rotterdam study (N=465). Associations between fasting serum metabolites and EAT volume were assessed using cross- sectional linear regression of individual- level data in MESA and validated in Rotterdam.RESULTS: A total of 23 571 metabolomic spectral variables were evaluated. In MESA, after adjustment for age, sex, and race and ethnicity, 38 metabolites were positively and 19 metabolites negatively associated with EAT at a false discovery rate P<0.01. Several metabolites were replicated in Rotterdam, including 1,5- anhydrosorbitol and N- acetyl (glycoproteins) that were positively associated with EAT and trimethylamine (phospholipids) that were inversely associated with EAT. Branched- chain amino acids (leucine, isoleucine, and valine) and 3- hydroxybutyrate were also associated with EAT in the Rotterdam study. In MESA, apolipoprotein B and very- low- density and intermediate- density lipoprotein fractions were positively associated with EAT and the majority of high- density lipoprotein subclasses were inversely associated with EAT. Associations were partially attenuated in MESA and fully attenuated in Rotterdam after further adjustment for health and socioeconomic factors. CONCLUSIONS: From?>20 000 metabolomic features, 1,5- anhydrosorbitol, glycoproteins, phospholipids, and atherogenic dyslipidemia markers emerged as significant markers of EAT. Further investigation is warranted to determine whether nuclear magnetic resonance–based metabolic profiling can improve EAT detection with implications for cardiometabolic health.

Original language	English
Article number	e039750
Journal	Journal of the American Heart Association
Volume	14
Issue number	13
DOIs	https://doi.org/10.1161/JAHA.124.039750
State	Published - Jun 18 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Funding

This research was supported by grant R01HL155718 from the National Heart, Lung, and Blood Institute, contracts 75N92020D00001, HHSN268201500003I, N01‐HC‐95159, 75N92020D00005, N01‐HC‐95160, 75N92020D00002, N01‐HC‐95161, 75N92020D00003, N01‐HC‐95162, 75N92020D00006, N01‐HC‐95163, 75N92020D00004, N01‐HC‐95164, 75N92020D00007, N01‐HC‐95165, N01‐HC‐95166, N01‐HC‐95167, N01‐HC‐95168 and N01‐HC‐95169 from the National Heart, Lung, and Blood Institute, and by grants R01HL085323 from the National Heart, Lung, and Blood Institute, and UL1‐TR‐000040, UL1‐TR‐001079, and UL1‐TR‐001420 from the National Center for Advancing Translational Sciences. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa‐nhlbi.org. This paper has been reviewed and approved by the MESA Publications and Presentations Committee. The Development of Combinatorial Biomarkers for Subclinical Atherosclerosis project was supported by a grant from the European Union Seventh Framework Programme (305422). The Rotterdam Study is supported by Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. This manuscript is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy project, which has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement number 875534. This joint undertaking support from the European Union's Horizon 2020 research and innovation program and European Federation of Pharmaceutical Industries and Associations and Type 1 Diabetes Exchange, Juvenile Diabetes Research Foundation, and Obesity Action Coalition.

ASJC Scopus Subject Areas

Cardiology and Cardiovascular Medicine

Keywords

atrial fibrillation
cohort
epicardial fat
metabolite
metabolomics
pericardial fat

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10.1161/JAHA.124.039750License: CC BY-NC-ND

Cite this

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title = "Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study",

abstract = "BACKGROUND: Excess epicardial adipose tissue (EAT) has been associated with cardiovascular diseases such as atrial fibrillation, coronary artery disease, and heart failure. The metabolomic signature of EAT is not well studied. METHODS: Untargeted 1H nuclear magnetic resonance metabolomics profiling of serum was performed (1- dimensional nuclear magnetic resonance, Carr–Purcell–Meiboom–Gill Echo Train Acquisition, lipidomics) and EAT was measured with computed tomography in MESA (Multi- Ethnic Study of Atherosclerosis; N=3936) and the Rotterdam study (N=465). Associations between fasting serum metabolites and EAT volume were assessed using cross- sectional linear regression of individual- level data in MESA and validated in Rotterdam.RESULTS: A total of 23 571 metabolomic spectral variables were evaluated. In MESA, after adjustment for age, sex, and race and ethnicity, 38 metabolites were positively and 19 metabolites negatively associated with EAT at a false discovery rate P<0.01. Several metabolites were replicated in Rotterdam, including 1,5- anhydrosorbitol and N- acetyl (glycoproteins) that were positively associated with EAT and trimethylamine (phospholipids) that were inversely associated with EAT. Branched- chain amino acids (leucine, isoleucine, and valine) and 3- hydroxybutyrate were also associated with EAT in the Rotterdam study. In MESA, apolipoprotein B and very- low- density and intermediate- density lipoprotein fractions were positively associated with EAT and the majority of high- density lipoprotein subclasses were inversely associated with EAT. Associations were partially attenuated in MESA and fully attenuated in Rotterdam after further adjustment for health and socioeconomic factors. CONCLUSIONS: From?>20 000 metabolomic features, 1,5- anhydrosorbitol, glycoproteins, phospholipids, and atherogenic dyslipidemia markers emerged as significant markers of EAT. Further investigation is warranted to determine whether nuclear magnetic resonance–based metabolic profiling can improve EAT detection with implications for cardiometabolic health.",

keywords = "atrial fibrillation, cohort, epicardial fat, metabolite, metabolomics, pericardial fat",

author = "Neeland, \{Ian J.\} and Fang Zhu and Goncalo Graca and Anastasios Lymperopoulos and Gianluca Iacobellis and Ali Farzaneh and Daniel Bos and Mohsen Ghanbari and Goldberger, \{Jeffrey J.\} and Maryam Kavousi and Philip Greenland",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.",

year = "2025",

month = jun,

day = "18",

doi = "10.1161/JAHA.124.039750",

language = "English",

volume = "14",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "American Heart Association Inc.",

number = "13",

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TY - JOUR

T1 - Metabolomics Profiling of Epicardial Adipose Tissue

T2 - MESA and the Rotterdam Study

AU - Neeland, Ian J.

AU - Zhu, Fang

AU - Graca, Goncalo

AU - Lymperopoulos, Anastasios

AU - Iacobellis, Gianluca

AU - Farzaneh, Ali

AU - Bos, Daniel

AU - Ghanbari, Mohsen

AU - Goldberger, Jeffrey J.

AU - Kavousi, Maryam

AU - Greenland, Philip

N1 - Publisher Copyright: © 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

PY - 2025/6/18

Y1 - 2025/6/18

N2 - BACKGROUND: Excess epicardial adipose tissue (EAT) has been associated with cardiovascular diseases such as atrial fibrillation, coronary artery disease, and heart failure. The metabolomic signature of EAT is not well studied. METHODS: Untargeted 1H nuclear magnetic resonance metabolomics profiling of serum was performed (1- dimensional nuclear magnetic resonance, Carr–Purcell–Meiboom–Gill Echo Train Acquisition, lipidomics) and EAT was measured with computed tomography in MESA (Multi- Ethnic Study of Atherosclerosis; N=3936) and the Rotterdam study (N=465). Associations between fasting serum metabolites and EAT volume were assessed using cross- sectional linear regression of individual- level data in MESA and validated in Rotterdam.RESULTS: A total of 23 571 metabolomic spectral variables were evaluated. In MESA, after adjustment for age, sex, and race and ethnicity, 38 metabolites were positively and 19 metabolites negatively associated with EAT at a false discovery rate P<0.01. Several metabolites were replicated in Rotterdam, including 1,5- anhydrosorbitol and N- acetyl (glycoproteins) that were positively associated with EAT and trimethylamine (phospholipids) that were inversely associated with EAT. Branched- chain amino acids (leucine, isoleucine, and valine) and 3- hydroxybutyrate were also associated with EAT in the Rotterdam study. In MESA, apolipoprotein B and very- low- density and intermediate- density lipoprotein fractions were positively associated with EAT and the majority of high- density lipoprotein subclasses were inversely associated with EAT. Associations were partially attenuated in MESA and fully attenuated in Rotterdam after further adjustment for health and socioeconomic factors. CONCLUSIONS: From?>20 000 metabolomic features, 1,5- anhydrosorbitol, glycoproteins, phospholipids, and atherogenic dyslipidemia markers emerged as significant markers of EAT. Further investigation is warranted to determine whether nuclear magnetic resonance–based metabolic profiling can improve EAT detection with implications for cardiometabolic health.

AB - BACKGROUND: Excess epicardial adipose tissue (EAT) has been associated with cardiovascular diseases such as atrial fibrillation, coronary artery disease, and heart failure. The metabolomic signature of EAT is not well studied. METHODS: Untargeted 1H nuclear magnetic resonance metabolomics profiling of serum was performed (1- dimensional nuclear magnetic resonance, Carr–Purcell–Meiboom–Gill Echo Train Acquisition, lipidomics) and EAT was measured with computed tomography in MESA (Multi- Ethnic Study of Atherosclerosis; N=3936) and the Rotterdam study (N=465). Associations between fasting serum metabolites and EAT volume were assessed using cross- sectional linear regression of individual- level data in MESA and validated in Rotterdam.RESULTS: A total of 23 571 metabolomic spectral variables were evaluated. In MESA, after adjustment for age, sex, and race and ethnicity, 38 metabolites were positively and 19 metabolites negatively associated with EAT at a false discovery rate P<0.01. Several metabolites were replicated in Rotterdam, including 1,5- anhydrosorbitol and N- acetyl (glycoproteins) that were positively associated with EAT and trimethylamine (phospholipids) that were inversely associated with EAT. Branched- chain amino acids (leucine, isoleucine, and valine) and 3- hydroxybutyrate were also associated with EAT in the Rotterdam study. In MESA, apolipoprotein B and very- low- density and intermediate- density lipoprotein fractions were positively associated with EAT and the majority of high- density lipoprotein subclasses were inversely associated with EAT. Associations were partially attenuated in MESA and fully attenuated in Rotterdam after further adjustment for health and socioeconomic factors. CONCLUSIONS: From?>20 000 metabolomic features, 1,5- anhydrosorbitol, glycoproteins, phospholipids, and atherogenic dyslipidemia markers emerged as significant markers of EAT. Further investigation is warranted to determine whether nuclear magnetic resonance–based metabolic profiling can improve EAT detection with implications for cardiometabolic health.

KW - atrial fibrillation

KW - cohort

KW - epicardial fat

KW - metabolite

KW - metabolomics

KW - pericardial fat

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UR - https://www.scopus.com/pages/publications/105010280000#tab=citedBy

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DO - 10.1161/JAHA.124.039750

M3 - Article

C2 - 40530511

AN - SCOPUS:105010280000

SN - 2047-9980

VL - 14

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

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M1 - e039750

ER -

Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study

Abstract

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ASJC Scopus Subject Areas

Keywords

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