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Urinary metabolic signatures of human adiposity

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ElliottRevisedTextaaa5680EditOS_inclRESPONSE_acceptedANDedited.docxAccepted version437.9 kBMicrosoft WordView/Open
SupplementaryMaterial_aaa5680_160215.docxSupporting information4.4 MBMicrosoft WordView/Open
Title: Urinary metabolic signatures of human adiposity
Authors: Elliott, P
Posma, JM
Chan, Q
Garcia-Perez, I
Wijeyesekera, A
Bictash, M
Ebbels, TMD
Ueshima, H
Zhao, L
Van Horn, L
Daviglus, M
Stamler, J
Holmes, E
Nicholson, JK
Item Type: Journal Article
Abstract: Obesity is a major public health problem worldwide. We used 24-hour urinary metabolic profiling by proton (1H) nuclear magnetic resonance (NMR) spectroscopy and ion exchange chromatography to characterize the metabolic signatures of adiposity in the U.S. (n = 1880) and UK (n = 444) cohorts of the INTERMAP (International Study of Macro- and Micronutrients and Blood Pressure) epidemiologic study. Metabolic profiling of urine samples collected over two 24-hour time periods 3 weeks apart showed reproducible patterns of metabolite excretion associated with adiposity. Exploratory analysis of the urinary metabolome using 1H NMR spectroscopy of the U.S. samples identified 29 molecular species, clustered in interconnecting metabolic pathways, that were significantly associated (P = 1.5 × 10−5 to 2.0 × 10−36) with body mass index (BMI); 25 of these species were also found in the UK validation cohort. We found multiple associations between urinary metabolites and BMI including urinary glycoproteins and N-acetyl neuraminate (related to renal function), trimethylamine, dimethylamine, 4-cresyl sulfate, phenylacetylglutamine and 2-hydroxyisobutyrate (gut microbial co-metabolites), succinate and citrate (tricarboxylic acid cycle intermediates), ketoleucine and the ketoleucine/leucine ratio (linked to skeletal muscle mitochondria and branched-chain amino acid metabolism), ethanolamine (skeletal muscle turnover), and 3-methylhistidine (skeletal muscle turnover and meat intake). We mapped the multiple BMI-metabolite relationships as part of an integrated systems network that describes the connectivities between the complex pathway and compartmental signatures of human adiposity.
Issue Date: 29-Apr-2015
Date of Acceptance: 10-Apr-2015
URI: http://hdl.handle.net/10044/1/79045
DOI: 10.1126/scitranslmed.aaa5680
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science
Start Page: 1
End Page: 16
Journal / Book Title: Science Translational Medicine
Volume: 7
Issue: 285
Copyright Statement: © 2015, American Association for the Advancement of Science. This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Translational Medicine on Vol. 7, ISsue 285, DOI: https://doi.org/10.1126/scitranslmed.aaa5680
Sponsor/Funder: National Institutes of Health
National Institutes of Health
Medical Research Council (MRC)
National Institute for Health Research
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Funder's Grant Number: 60024563 ICL
2R01HL084228-05A1
MR/L01341X/1
NF-SI-0611-10136
MC_PC_12025
RDC01 79560
PDF-2012-05-456
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
BODY-MASS INDEX
GUT MICROBES
PROLINE BETAINE
BLOOD-PRESSURE
MUSCLE MASS
BIOMARKERS
DISEASE
OBESITY
WOMEN
DIET
Adiposity
Amino Acids, Branched-Chain
Body Mass Index
Energy Metabolism
Humans
Metabolomics
Muscle, Skeletal
Obesity
Proton Magnetic Resonance Spectroscopy
Muscle, Skeletal
Humans
Obesity
Amino Acids, Branched-Chain
Body Mass Index
Energy Metabolism
Adiposity
Metabolomics
Proton Magnetic Resonance Spectroscopy
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
BODY-MASS INDEX
GUT MICROBES
PROLINE BETAINE
BLOOD-PRESSURE
MUSCLE MASS
BIOMARKERS
DISEASE
OBESITY
WOMEN
DIET
06 Biological Sciences
11 Medical and Health Sciences
Publication Status: Published
Article Number: ARTN 285ra62
Online Publication Date: 2015-04-29
Appears in Collections:School of Public Health