title: Abdominal obesity and circulating metabolites: A twin study approach.
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.
  
  
  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 (rg) 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 (rg=0.40), glycoprotein (rg=0.37), serum triglycerides (rg=0.36), BCAAs (rg=0.30-0.40), HDL particle diameter (rg=-0.33) and HDL cholesterol (rg=-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.
authors.affiliation: Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland. Electronic address: leonie-helen.bogl@helsinki.fi.
authors.forename: Leonie H
authors.initials: LH
authors.lastname: Bogl
authors.affiliation: Obesity Research Unit, Research programs unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: Sanna M
authors.initials: SM
authors.lastname: Kaye
authors.affiliation: Obesity Research Unit, Research programs unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland; Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Rämö
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.affiliation: Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Hakkarainen
authors.affiliation: Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland.
authors.forename: Jesper
authors.initials: J
authors.lastname: Lundbom
authors.affiliation: Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Lundbom
authors.affiliation: Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ortega-Alonso
authors.affiliation: Obesity Research Unit, Research programs unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland; Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Aila
authors.initials: A
authors.lastname: Rissanen
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland; Oulu University Hospital, Oulu, Finland; Computational Medicine, School of Social and Community Medicine and the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.affiliation: Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland; Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland; Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: Obesity Research Unit, Research programs unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland; Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland; Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Pietiläinen
mesh_terms: D015502:Absorptiometry, Photon; D050154:Adiposity / Q000235:genetics; D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D056128:Obesity, Abdominal / Q000097:blood* / Q000235:genetics; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D055105:Waist Circumference; D055815:Young Adult
chemical_list: D000597:Amino Acids, Branched-Chain; D008074:Lipoproteins; D002097:C-Reactive Protein
keywords: Bivariate twin model; Genetic correlation; Obesity measures; Serum metabolites; Twin study