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

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

doi:10.1210/clinem/dgab922

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

J Clin Endocrinol Metab. 2022 Apr 19;107(5):1337-1345. doi: 10.1210/clinem/dgab922.

Authors

Lars Lind¹, Samira Salihovic², Johan Sundström¹, Sölve Elmståhl³, Ulf Hammar¹, Koen Dekkers¹, Johan Ärnlöv^{4

5}, J Gustav Smith^{6

7

8}, Gunnar Engström⁹, Tove Fall¹

Affiliations

¹ Department of Medical Sciences, Uppsala University, Sweden.
² Inflammatory Response and Infection Susceptibility Centre, School of Medical Sciences, Örebro University, Örebro, Sweden.
³ Department of Clinical Sciences, Division of Geriatric Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
⁴ Division of Family Medicine and Primary Care, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Huddinge, Sweden.
⁵ School of Health and Social Studies, Dalarna University, Falun, Sweden.
⁶ Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital , Lund, Sweden.
⁷ The Wallenberg Laboratory/Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University and the Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁸ Wallenberg Center for Molecular Medicine and Lund University Diabetes Center, Lund University, Lund, Sweden.
⁹ Department of Clinical Sciences, Lund University, Malmö, Sweden.

PMID: 34984454
DOI: 10.1210/clinem/dgab922

Abstract

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.

Keywords: epidemiology; insulin resistance; metabolic syndrome; metabolomics; obesity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Body Mass Index
Cross-Sectional Studies
Humans
Insulin Resistance*
Metabolic Syndrome*
Obesity / complications
Sphingolipids
Waist Circumference

Substances

Sphingolipids

Abstract

Publication types

MeSH terms

Substances

Grants and funding