Metabolomics Profiling of Visceral Adipose Tissue

Results From MESA and the NEO Study

Ian J Neeland, Sebastiaan C. Boone, Dennis O. Mook-Kanamori, Colby Ayers, Roelof A.J. Smit, Ioanna Tzoulaki, Ibrahim Karaman, Claire Boulange, Dhananjay Vaidya, Naresh Punjabi, Matthew Allison, David M. Herrington, J. Wouter Jukema, Frits R. Rosendaal, Hildo J. Lamb, Ko Willems van Dijk, Philip Greenland, Renée de Mutsert

Research output: Contribution to journalArticle

Abstract

Background Identifying associations between serum metabolites and visceral adipose tissue ( VAT ) could provide novel biomarkers of VAT and insights into the pathogenesis of obesity-related diseases. We aimed to discover and replicate metabolites reflecting pathways related to VAT . Methods and Results Associations between fasting serum metabolites and VAT area (by computed tomography or magnetic resonance imaging) were assessed with cross-sectional linear regression of individual-level data from participants in MESA (Multi-Ethnic Study of Atherosclerosis; discovery, N=1103) and the NEO (Netherlands Epidemiology of Obesity) study (replication, N=2537). Untargeted 1H nuclear magnetic resonance metabolomics profiling of serum was performed in MESA, and metabolites were replicated in the NEO study using targeted 1H nuclear magnetic resonance spectroscopy. A total of 30 590 metabolomic spectral variables were evaluated. After adjustment for age, sex, race/ethnicity, socioeconomic status, smoking, physical activity, glucose/lipid-lowering medication, and body mass index, 2104 variables representing 24 nonlipid and 49 lipid/lipoprotein subclass metabolites remained significantly associated with VAT ( P=4.88×10-20-1.16×10-3). These included conventional metabolites, amino acids, acetylglycoproteins, intermediates of glucose and hepatic metabolism, organic acids, and subclasses of apolipoproteins, cholesterol, phospholipids, and triglycerides. Metabolites mapped to 31 biochemical pathways, including amino acid substrate use/metabolism and glycolysis/gluconeogenesis. In the replication cohort, acetylglycoproteins, branched-chain amino acids, lactate, glutamine (inversely), and atherogenic lipids remained associated with VAT ( P=1.90×10-35-8.46×10-7), with most associations remaining after additional adjustment for surrogates of VAT (glucose level, waist circumference, and serum triglycerides), reflecting novel independent associations. Conclusions We identified and replicated a metabolite panel associated with VAT in 2 community-based cohorts. These findings persisted after adjustment for body mass index and appear to define a metabolic signature of visceral adiposity.

Original languageEnglish (US)
Pages (from-to)e010810
JournalJournal of the American Heart Association
Volume8
Issue number9
DOIs
StatePublished - May 7 2019

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Metabolomics
Intra-Abdominal Fat
Netherlands
Epidemiology
Obesity
Serum
Lipids
Glucose
Triglycerides
Body Mass Index
Magnetic Resonance Spectroscopy
Amino Acids
Branched Chain Amino Acids
Gluconeogenesis
Apolipoproteins
Adiposity
Waist Circumference
Glycolysis
Glutamine
Social Class

Keywords

  • adipose tissue
  • cohort
  • metabolite
  • metabolomics
  • obesity
  • visceral adipose tissue

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Neeland, I. J., Boone, S. C., Mook-Kanamori, D. O., Ayers, C., Smit, R. A. J., Tzoulaki, I., ... de Mutsert, R. (2019). Metabolomics Profiling of Visceral Adipose Tissue: Results From MESA and the NEO Study. Journal of the American Heart Association, 8(9), e010810. https://doi.org/10.1161/JAHA.118.010810

Metabolomics Profiling of Visceral Adipose Tissue : Results From MESA and the NEO Study. / Neeland, Ian J; Boone, Sebastiaan C.; Mook-Kanamori, Dennis O.; Ayers, Colby; Smit, Roelof A.J.; Tzoulaki, Ioanna; Karaman, Ibrahim; Boulange, Claire; Vaidya, Dhananjay; Punjabi, Naresh; Allison, Matthew; Herrington, David M.; Jukema, J. Wouter; Rosendaal, Frits R.; Lamb, Hildo J.; van Dijk, Ko Willems; Greenland, Philip; de Mutsert, Renée.

In: Journal of the American Heart Association, Vol. 8, No. 9, 07.05.2019, p. e010810.

Research output: Contribution to journalArticle

Neeland, IJ, Boone, SC, Mook-Kanamori, DO, Ayers, C, Smit, RAJ, Tzoulaki, I, Karaman, I, Boulange, C, Vaidya, D, Punjabi, N, Allison, M, Herrington, DM, Jukema, JW, Rosendaal, FR, Lamb, HJ, van Dijk, KW, Greenland, P & de Mutsert, R 2019, 'Metabolomics Profiling of Visceral Adipose Tissue: Results From MESA and the NEO Study', Journal of the American Heart Association, vol. 8, no. 9, pp. e010810. https://doi.org/10.1161/JAHA.118.010810
Neeland, Ian J ; Boone, Sebastiaan C. ; Mook-Kanamori, Dennis O. ; Ayers, Colby ; Smit, Roelof A.J. ; Tzoulaki, Ioanna ; Karaman, Ibrahim ; Boulange, Claire ; Vaidya, Dhananjay ; Punjabi, Naresh ; Allison, Matthew ; Herrington, David M. ; Jukema, J. Wouter ; Rosendaal, Frits R. ; Lamb, Hildo J. ; van Dijk, Ko Willems ; Greenland, Philip ; de Mutsert, Renée. / Metabolomics Profiling of Visceral Adipose Tissue : Results From MESA and the NEO Study. In: Journal of the American Heart Association. 2019 ; Vol. 8, No. 9. pp. e010810.
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AU - Neeland, Ian J

AU - Boone, Sebastiaan C.

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AU - Ayers, Colby

AU - Smit, Roelof A.J.

AU - Tzoulaki, Ioanna

AU - Karaman, Ibrahim

AU - Boulange, Claire

AU - Vaidya, Dhananjay

AU - Punjabi, Naresh

AU - Allison, Matthew

AU - Herrington, David M.

AU - Jukema, J. Wouter

AU - Rosendaal, Frits R.

AU - Lamb, Hildo J.

AU - van Dijk, Ko Willems

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AU - de Mutsert, Renée

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N2 - Background Identifying associations between serum metabolites and visceral adipose tissue ( VAT ) could provide novel biomarkers of VAT and insights into the pathogenesis of obesity-related diseases. We aimed to discover and replicate metabolites reflecting pathways related to VAT . Methods and Results Associations between fasting serum metabolites and VAT area (by computed tomography or magnetic resonance imaging) were assessed with cross-sectional linear regression of individual-level data from participants in MESA (Multi-Ethnic Study of Atherosclerosis; discovery, N=1103) and the NEO (Netherlands Epidemiology of Obesity) study (replication, N=2537). Untargeted 1H nuclear magnetic resonance metabolomics profiling of serum was performed in MESA, and metabolites were replicated in the NEO study using targeted 1H nuclear magnetic resonance spectroscopy. A total of 30 590 metabolomic spectral variables were evaluated. After adjustment for age, sex, race/ethnicity, socioeconomic status, smoking, physical activity, glucose/lipid-lowering medication, and body mass index, 2104 variables representing 24 nonlipid and 49 lipid/lipoprotein subclass metabolites remained significantly associated with VAT ( P=4.88×10-20-1.16×10-3). These included conventional metabolites, amino acids, acetylglycoproteins, intermediates of glucose and hepatic metabolism, organic acids, and subclasses of apolipoproteins, cholesterol, phospholipids, and triglycerides. Metabolites mapped to 31 biochemical pathways, including amino acid substrate use/metabolism and glycolysis/gluconeogenesis. In the replication cohort, acetylglycoproteins, branched-chain amino acids, lactate, glutamine (inversely), and atherogenic lipids remained associated with VAT ( P=1.90×10-35-8.46×10-7), with most associations remaining after additional adjustment for surrogates of VAT (glucose level, waist circumference, and serum triglycerides), reflecting novel independent associations. Conclusions We identified and replicated a metabolite panel associated with VAT in 2 community-based cohorts. These findings persisted after adjustment for body mass index and appear to define a metabolic signature of visceral adiposity.

AB - Background Identifying associations between serum metabolites and visceral adipose tissue ( VAT ) could provide novel biomarkers of VAT and insights into the pathogenesis of obesity-related diseases. We aimed to discover and replicate metabolites reflecting pathways related to VAT . Methods and Results Associations between fasting serum metabolites and VAT area (by computed tomography or magnetic resonance imaging) were assessed with cross-sectional linear regression of individual-level data from participants in MESA (Multi-Ethnic Study of Atherosclerosis; discovery, N=1103) and the NEO (Netherlands Epidemiology of Obesity) study (replication, N=2537). Untargeted 1H nuclear magnetic resonance metabolomics profiling of serum was performed in MESA, and metabolites were replicated in the NEO study using targeted 1H nuclear magnetic resonance spectroscopy. A total of 30 590 metabolomic spectral variables were evaluated. After adjustment for age, sex, race/ethnicity, socioeconomic status, smoking, physical activity, glucose/lipid-lowering medication, and body mass index, 2104 variables representing 24 nonlipid and 49 lipid/lipoprotein subclass metabolites remained significantly associated with VAT ( P=4.88×10-20-1.16×10-3). These included conventional metabolites, amino acids, acetylglycoproteins, intermediates of glucose and hepatic metabolism, organic acids, and subclasses of apolipoproteins, cholesterol, phospholipids, and triglycerides. Metabolites mapped to 31 biochemical pathways, including amino acid substrate use/metabolism and glycolysis/gluconeogenesis. In the replication cohort, acetylglycoproteins, branched-chain amino acids, lactate, glutamine (inversely), and atherogenic lipids remained associated with VAT ( P=1.90×10-35-8.46×10-7), with most associations remaining after additional adjustment for surrogates of VAT (glucose level, waist circumference, and serum triglycerides), reflecting novel independent associations. Conclusions We identified and replicated a metabolite panel associated with VAT in 2 community-based cohorts. These findings persisted after adjustment for body mass index and appear to define a metabolic signature of visceral adiposity.

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