Abdominal obesity and circulating metabolites : A twin study approach

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Bogl , L H , Kaye , S M , Ramo , J T , Kangas , A J , Soininen , P , Hakkarainen , A , Lundbom , J , Lundbom , N , Ortega-Alonso , A , Rissanen , A , Ala-Korpela , M , Kaprio , J & Pietilainen , K H 2016 , ' Abdominal obesity and circulating metabolites : A twin study approach ' , Metabolism, clinical and experimental , vol. 65 , no. 3 , pp. 111-121 . https://doi.org/10.1016/j.metabol.2015.10.027

Title: Abdominal obesity and circulating metabolites : A twin study approach
Author: Bogl, Leonie H.; Kaye, Sanna M.; Ramo, Joel T.; Kangas, Antti J.; Soininen, Pasi; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Ortega-Alonso, Alfredo; Rissanen, Aila; Ala-Korpela, Mika; Kaprio, Jaakko; Pietilainen, Kirsi H.
Contributor organization: Department of General Practice and Primary Health Care
Diabetes and Obesity Research Program
Institute for Molecular Medicine Finland
Research Programs Unit
Department of Diagnostics and Therapeutics
Department of Psychiatry
Jaakko Kaprio / Principal Investigator
Kirsi Hannele Pietiläinen / Principal Investigator
Department of Medicine
HUS Psychiatry
HUS Internal Medicine and Rehabilitation
Developmental Psychology Research Group
Complex Disease Genetics
Genomics of Neurological and Neuropsychiatric Disorders
Genetic Epidemiology
Date: 2016-03
Language: eng
Number of pages: 11
Belongs to series: Metabolism, clinical and experimental
ISSN: 0026-0495
DOI: https://doi.org/10.1016/j.metabol.2015.10.027
URI: http://hdl.handle.net/10138/223885
Abstract: Objective. To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors. Subjects and methods. Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (r(g)) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference >= 3 kg/m(2)). Results. Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (r(g) = 0.40), glycoprotein (r(g) = 0.37), serum triglycerides (r(g) = 0.36), BCAAs (r(g) = 0.30-0.40), HDL particle diameter (r(g) = -0.33) and HDL cholesterol (r(g) = -0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins. Conclusions. A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability. (C) 2015 Elsevier Inc. All rights reserved.
Subject: Twin study
Bivariate twin model
Genetic correlation
Serum metabolites
Obesity measures
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion

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