TY - JOUR
T1 - Metabolomics Profiling of Visceral Adipose Tissue
T2 - Results From MESA and the NEO Study
AU - Neeland, Ian J.
AU - Boone, Sebastiaan C.
AU - Mook-Kanamori, Dennis O.
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
AU - Greenland, Philip
AU - de Mutsert, Renée
N1 - Funding Information:
Dr Neeland has received honoraria, consulting and speaker’s bureau fees, and travel support from Boehringer-Ingelheim/ Lilly Alliance (significant), has received a research grant from Novo Nordisk (significant), and is a member of the scientific advisory board of AMRA Medical (modest). The remaining authors have no disclosures to report.
Funding Information:
Dr Neeland is supported by grant K23 DK106520 from the National Institutes of Health (NIH) and by the Dedman Family Scholarship in Clinical Care from the University of Texas Southwestern. MESA (Multi-Ethnic Study of Atherosclerosis) was supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI); and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences. Dr Allison was supported by funding for MESA Abdominal Body Composition Ancillary study from the NHLBI (R01-HL088451). Dr Karaman acknowledges support from the European Union PhenoMeNal Project (Horizon 2020, 654241). The Development of Combinatorial Biomarkers for Subclinical Atherosclerosis project was supported by a grant from the European Union Seventh Framework Programme (305422). The NEO (Netherlands Epidemiology in Obesity) study is supported by the participating departments, the division, and the Board of Directors of the Leiden University Medical Center, and by the Leiden University, Research Profile Area “Vascular and Regenerative Medicine.” We acknowledge support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON2014-02 ENERGISE). Dr Mook-Kanamori is supported by the Dutch Science Organization (ZonMW-VENI Grant 916.14.023). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2019/5/7
Y1 - 2019/5/7
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.
KW - adipose tissue
KW - cohort
KW - metabolite
KW - metabolomics
KW - obesity
KW - visceral adipose tissue
UR - http://www.scopus.com/inward/record.url?scp=85065315568&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065315568&partnerID=8YFLogxK
U2 - 10.1161/JAHA.118.010810
DO - 10.1161/JAHA.118.010810
M3 - Article
C2 - 31017036
AN - SCOPUS:85065315568
SN - 2047-9980
VL - 8
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 9
M1 - e010810
ER -
