The metabolomic profiling of total fat and fat distribution in a multi-cohort study of women and men

• Published in: Scientific reports Vol. 13; no. 1; p. 11129
• Main Authors: Zheng, Rui, Michaëlsson, Karl, Fall, Tove, Elmståhl, Sölve, Lind, Lars
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10-07-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4017; 692/499; 692/53; Amino acids; Amino Acids, Branched-Chain; Biosynthesis; Chromatography, Liquid; Cohort analysis; Cohort Studies; Cross-Sectional Studies; Female; Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi; Health Sciences; Humanities and Social Sciences; Humans; Hälsovetenskap; Lipid metabolism; Liquid chromatography; Male; Mass spectrometry; Mass spectroscopy; Medical and Health Sciences; Medicin och hälsovetenskap; Metabolic pathways; Metabolism; Metabolites; Metabolomics; multidisciplinary; Protein biosynthesis; Protein synthesis; Public Health, Global Health, Social Medicine and Epidemiology; Replication; Science; Science (multidisciplinary); Women
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-38318-z

Currently studies aiming for the comprehensive metabolomics profiling of measured total fat (%) as well as fat distribution in both sexes are lacking. In this work, bioimpedance analysis was applied to measure total fat (%) and fat distribution (trunk to leg ratio). Liquid chromatography-mass spectrometry-based untargeted metabolomics was employed to profile the metabolic signatures of total fat (%) and fat distribution in 3447 participants from three Swedish cohorts (EpiHealth, POEM and PIVUS) using a discovery-replication cross-sectional study design. Total fat (%) and fat distribution were associated with 387 and 120 metabolites in the replication cohort, respectively. Enriched metabolic pathways for both total fat (%) and fat distribution included protein synthesis, branched-chain amino acids biosynthesis and metabolism, glycerophospholipid metabolism and sphingolipid metabolism. Four metabolites were mainly related to fat distribution: glutarylcarnitine (C5-DC), 6-bromotryptophan, 1-stearoyl-2-oleoyl-GPI (18:0/18:1) and pseudouridine. Five metabolites showed different associations with fat distribution in men and women: quinolinate, (12Z)-9,10-dihydroxyoctadec-12-enoate (9,10-DiHOME), two sphingomyelins and metabolonic lactone sulfate. To conclude, total fat (%) and fat distribution were associated with a large number of metabolites, but only a few were exclusively associated with fat distribution and of those metabolites some were associated with sex*fat distribution. Whether these metabolites mediate the undesirable effects of obesity on health outcomes remains to be further investigated.