PLoS Medicine (Dec 2014)

Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change.

  • Peter Würtz,
  • Qin Wang,
  • Antti J Kangas,
  • Rebecca C Richmond,
  • Joni Skarp,
  • Mika Tiainen,
  • Tuulia Tynkkynen,
  • Pasi Soininen,
  • Aki S Havulinna,
  • Marika Kaakinen,
  • Jorma S Viikari,
  • Markku J Savolainen,
  • Mika Kähönen,
  • Terho Lehtimäki,
  • Satu Männistö,
  • Stefan Blankenberg,
  • Tanja Zeller,
  • Jaana Laitinen,
  • Anneli Pouta,
  • Pekka Mäntyselkä,
  • Mauno Vanhala,
  • Paul Elliott,
  • Kirsi H Pietiläinen,
  • Samuli Ripatti,
  • Veikko Salomaa,
  • Olli T Raitakari,
  • Marjo-Riitta Järvelin,
  • George Davey Smith,
  • Mika Ala-Korpela

DOI
https://doi.org/10.1371/journal.pmed.1001765
Journal volume & issue
Vol. 11, no. 12
p. e1001765

Abstract

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BackgroundIncreased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood.Methods and findingsWe used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16-39 y; 51% women; mean ± standard deviation BMI 24 ± 4 kg/m(2)). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (pConclusionsMendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary.