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J Proteome Res. 2017 Sep 1;16(9):3137-3146. doi: 10.1021/acs.jproteome.6b01062. Epub 2017 Aug 11.

Blood Metabolic Signatures of Body Mass Index: A Targeted Metabolomics Study in the EPIC Cohort.

Author information

1
International Agency for Research on Cancer , Section of Nutrition and Metabolism, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
2
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford , Richard Doll Building, Oxford OX3 7LF, United Kingdom.
3
Aarhus University , Department of Public Health, Section for Epidemiology, Bartholins Alle 2, DK-8000 Aarhus C, Denmark.
4
Danish Cancer Society Research Center , Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
5
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) , Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany.
6
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) , Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
7
Hellenic Health Foundation , Alexandroupoleos 23, Athens 11527, Greece.
8
WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept. of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School , Mikras Asias 75, Goudi GR,11527 Athens, Greece.
9
Department of Epidemiology, Harvard School of Public Health , 677 Huntington Avenue, Boston, Massachusetts 02115, United States.
10
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO) , Ponte Nuovo, Via delle Oblate n.4, Padiglione 28-A Mario Fiori, 50141 Florence, Italy.
11
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori , Via Venezian, 1, 20133 Milan, Italy.
12
Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital , Via Dante 109, 97100 ASP Ragusa, Italy.
13
Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health , St Mary's Campus, Norfolk Place, W2 1PG London, U.K.
14
HuGeF Foundation , Via Nizza 52, 10126 Turin, Italy.
15
Dipartimento di Medicina Clinica e Chirurgia, Medical School of Naples, Federico II University , Via Sergio Pansini, 5, 80131 Naples, Italy.
16
EPIC Asturias, Public Health Directorate , Asturias, Ciriaco Miguel Vigil St, 9, 33006 Oviedo, Spain.
17
Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. Granada, Hospitales Universitarios de Granada/Universidad de Granada , Cuesta del Observatorio, 4, 18011 Granada, Spain.
18
CIBER Epidemiología y Salud Pública (CIBERESP) , Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain.
19
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca , Ronda de Levante, 11, 30008 Murcia, Spain.
20
Navarra Public Health Institute , C/Leyre, 15, 31003 Pamplona, Spain.
21
IdiSNA, Navarra Institute for Health Research , C/Irunlarrea, 3, 31008 Pamplona, Spain.
22
Public Health Division of Gipuzkoa, Instituto BIO-Donostia, Basque Government , Av. Navarra 4, 20013 San Sebastian, Spain.
23
Unit of Nutrition and Cancer. Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL , Av. Gran Via de l'Hospitalet 199-203, 08908 L'Hospitalet de Llobregat, Spain.
24
Department of Clinical Sciences Malmö, Lund University , Jan Waldenströms gata 35, 20502 Malmö, Sweden.
25
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM) , PO Box 1, 3720 BA Bilthoven, The Netherlands.
26
Department of Gastroenterology and Hepatology, University Medical Center Utrecht , Room number F02.649, Internal mail no F02.618, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
27
Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya , Pantai Valley, 50603 Kuala Lumpur, Malaysia.
28
Dept of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht , STR 6.131, PO Box 85500, 3508GA Utrecht, The Netherlands.
29
Medical Research Council Epidemiology Unit, MRC Epidemiology Unit, University of Cambridge , School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, U.K.
30
Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge , Cambridge CB1 8RN, U.K.

Abstract

Metabolomics is now widely used to characterize metabolic phenotypes associated with lifestyle risk factors such as obesity. The objective of the present study was to explore the associations of body mass index (BMI) with 145 metabolites measured in blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolites were measured in blood from 392 men from the Oxford (UK) cohort (EPIC-Oxford) and in 327 control subjects who were part of a nested case-control study on hepatobiliary carcinomas (EPIC-Hepatobiliary). Measured metabolites included amino acids, acylcarnitines, hexoses, biogenic amines, phosphatidylcholines, and sphingomyelins. Linear regression models controlled for potential confounders and multiple testing were run to evaluate the associations of metabolite concentrations with BMI. 40 and 45 individual metabolites showed significant differences according to BMI variations, in the EPIC-Oxford and EPIC-Hepatobiliary subcohorts, respectively. Twenty two individual metabolites (kynurenine, one sphingomyelin, glutamate and 19 phosphatidylcholines) were associated with BMI in both subcohorts. The present findings provide additional knowledge on blood metabolic signatures of BMI in European adults, which may help identify mechanisms mediating the relationship of BMI with obesity-related diseases.

KEYWORDS:

blood; body mass index; metabolic profiling; obesity; targeted metabolome

PMID:
28758405
PMCID:
PMC6198936
DOI:
10.1021/acs.jproteome.6b01062
[Indexed for MEDLINE]
Free PMC Article

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