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Gustav Smith

Associate professor

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Metabolic Profiling of Obesity With and Without the Metabolic Syndrome : A Multisample Evaluation

Author

  • Lars Lind
  • Samira Salihovic
  • Johan Sundström
  • Sölve Elmståhl
  • Ulf Hammar
  • Koen Dekkers
  • Johan Ärnlöv
  • J. Gustav Smith
  • Gunnar Engström
  • Tove Fall

Summary, in English

Context: There is a dispute whether obesity without major metabolic derangements may represent a benign condition or not. Objective: We aimed to compare the plasma metabolome in obese subjects without metabolic syndrome (MetS) with normal-weight subjects without MetS and with obese subjects with MetS. Methods: This was a cross-sectional study at 2 academic centers in Sweden. Individuals from 3 population-based samples (EpiHealth, n=2342, SCAPIS-Uppsala, n=4985, and SCAPIS-Malmö, n=3978) were divided into groups according to their body mass index (BMI) and presence/absence of MetS (National Cholesterol Education Program [NCEP]/consensus criteria). In total, 791 annotated endogenous metabolites were measured by ultra-performance liquid chromatography-tandem mass spectrometry. Results: We observed major differences in metabolite profiles (427 metabolites) between obese (BMI≥30 kg/m2) and normal-weight (BMI<25 kg/m2) subjects without MetS after adjustment for major lifestyle factors. Pathway enrichment analysis highlighted branch-chained and aromatic amino acid synthesis/metabolism, aminoacyl-tRNA biosynthesis, and sphingolipid metabolism. The same pathways, and similar metabolites, were also highlighted when obese subjects with and without MetS were compared despite adjustment for BMI and waist circumference, or when the metabolites were related to BMI and number of MetS components in a continuous fashion. Similar metabolites and pathways were also related to insulin sensitivity (Matsuda index) in a separate study (POEM, n=501). Conclusion: Our data suggest a graded derangement of the circulating metabolite profile from lean to obese to MetS, in particular for metabolites involved in amino acid synthesis/metabolism and sphingolipid metabolism. Insulin resistance is a plausible mediator of this gradual metabolic deterioration.

Department/s

  • Geriatrics
  • EpiHealth: Epidemiology for Health
  • WCMM-Wallenberg Centre for Molecular Medicine
  • Heart Failure and Mechanical Support
  • Cardiovascular Epigenetics
  • Cardiology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Molecular Epidemiology and Cardiology
  • Cardiovascular Research - Epidemiology

Publishing year

2022-05-01

Language

English

Pages

1337-1345

Publication/Series

Journal of Clinical Endocrinology and Metabolism

Volume

107

Issue

5

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Endocrinology and Diabetes

Keywords

  • epidemiology
  • insulin resistance
  • metabolic syndrome
  • metabolomics
  • obesity

Status

Published

Research group

  • Geriatrics
  • Heart Failure and Mechanical Support
  • Cardiovascular Epigenetics
  • Molecular Epidemiology and Cardiology
  • Cardiovascular Research - Epidemiology

ISBN/ISSN/Other

  • ISSN: 0021-972X