Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study
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...
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Wiley
2025-07-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.039750 |
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| author | Ian J. Neeland Fang Zhu Goncalo Graca Anastasios Lymperopoulos Gianluca Iacobellis Ali Farzaneh Daniel Bos Mohsen Ghanbari Jeffrey J. Goldberger Maryam Kavousi Philip Greenland |
| author_facet | Ian J. Neeland Fang Zhu Goncalo Graca Anastasios Lymperopoulos Gianluca Iacobellis Ali Farzaneh Daniel Bos Mohsen Ghanbari Jeffrey J. Goldberger Maryam Kavousi Philip Greenland |
| author_sort | Ian J. Neeland |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-01b6386b77fa443fa910454cfa07c818 |
| institution | DOAJ |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-01b6386b77fa443fa910454cfa07c8182025-08-20T03:09:31ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-07-01141310.1161/JAHA.124.039750Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam StudyIan J. Neeland0Fang Zhu1Goncalo Graca2Anastasios Lymperopoulos3Gianluca Iacobellis4Ali Farzaneh5Daniel Bos6Mohsen Ghanbari7Jeffrey J. Goldberger8Maryam Kavousi9Philip Greenland10Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine Cleveland OH USADepartment of Epidemiology Erasmus MC University Medical Center Rotterdam The NetherlandsSection of Bioinformatics, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction Faculty of Medicine, Imperial College London London United KingdomDepartment of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy Nova Southeastern University Fort Lauderdale FL USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine Miller School of Medicine University of Miami Miami FL USADepartment of Epidemiology Erasmus MC University Medical Center Rotterdam The NetherlandsDepartment of Epidemiology Erasmus MC University Medical Center Rotterdam The NetherlandsDepartment of Epidemiology Erasmus MC University Medical Center Rotterdam The NetherlandsCardiovascular Division, Department of Medicine Miller School of Medicine University of Miami Miami FL USADepartment of Epidemiology Erasmus MC University Medical Center Rotterdam The NetherlandsDepartment of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago IL USABackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.124.039750atrial fibrillationcohortepicardial fatmetabolitemetabolomicspericardial fat |
| spellingShingle | Ian J. Neeland Fang Zhu Goncalo Graca Anastasios Lymperopoulos Gianluca Iacobellis Ali Farzaneh Daniel Bos Mohsen Ghanbari Jeffrey J. Goldberger Maryam Kavousi Philip Greenland Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atrial fibrillation cohort epicardial fat metabolite metabolomics pericardial fat |
| title | Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study |
| title_full | Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study |
| title_fullStr | Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study |
| title_full_unstemmed | Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study |
| title_short | Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study |
| title_sort | metabolomics profiling of epicardial adipose tissue mesa and the rotterdam study |
| topic | atrial fibrillation cohort epicardial fat metabolite metabolomics pericardial fat |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.039750 |
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