{
  "abstract": "Background/Objectives: Metabolic syndrome (MetS) is a heterogeneous cluster of cardiometabolic risk factors whose underlying molecular heterogeneity remains incompletely understood. Methods: Targeted metabolomics (388 metabolites) and untargeted proteomics (842 proteins) were analyzed in the KORA FF4 study (n = 1921). Multivariable regression, LASSO, and Multi-Omics Factor Analysis (MOFA) were applied to identify MetS-associated signatures. As a secondary analysis, soft-clustering archetypal analysis based on 22 clinical variables was performed within the MetS subgroup (n = 582) to identify extreme clinical subphenotypes. Results: A total of 117 metabolites and 70 proteins were associated with MetS, including five metabolites and eight proteins shared across all MetS traits. Key metabolomic features comprised diacylglycerols, triglyceride score, hexoses, and branched-chain amino acids. Prominent proteins included APOC4, APOE, APOB, APOD, APOF, adiponectin, LBP, and SHBG, reflecting alterations in lipid metabolism, inflammation, and metabolic regulation. MOFA identified a latent factor strongly linked to MetS, integrating signatures of lipid metabolism, insulin resistance, and inflammation. Archetypal analysis identified extreme MetS profiles and associated with metabolites and proteins shared across all Mets. Conclusions: Integrated multi-omics analysis revealed MetS-associated molecular signatures characterized primarily by dysregulated lipid metabolism, insulin resistance, and chronic low-grade inflammation. Secondary archetypal analysis highlighted clinical heterogeneity at the extreme boundaries of MetS while supporting a shared molecular foundation. These findings highlight the value of combining clinical, metabolomics and proteomics to improve characterization of MetS heterogeneity and inform future precision risk stratification.",
  "abstract_shown": true,
  "affiliations": [
    "Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany",
    "Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany",
    "Chair of Epidemiology, Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Faculty of Medicine, Ludwig-Maximilians-University München, Marchioninistraße 15, 81377 München, Germany",
    "German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany",
    "Department of Biochemistry, Faculty of Science, Federal University of Lafia, PMB 146, Lafia 950101, Nigeria",
    "Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany",
    "Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA",
    "Bioinformatics Core, Weill Cornell Medical College, Qatar Education City, Doha P.O. Box 24144, Qatar",
    "Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany",
    "Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore",
    "Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia",
    "Metabolomics and Proteomics Core, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany",
    "Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany",
    "German Center for Diabetes Research (DZD), Partner Düsseldorf, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany",
    "Chair of Analytical Food Chemistry, TUM School of Life Sciences, Technical University of Munich, Freising-Weihenstephan, Maximus-von-Imhof-Forum 2, 85354 Freising, Germany",
    "Deutsches Herzzentrum München, Technische Universität München, 80333 Munich, Germany",
    "German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, 80336 Munich, Germany",
    "Institute of Epidemiology and Medical Biometry, University of Ulm, 89081 Ulm, Germany"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Homa Bazireh",
      "orcid": "0000-0001-5840-7063"
    },
    {
      "affs": [
        0,
        1,
        4
      ],
      "name": "Esienanwan Esien Efiong",
      "orcid": "0000-0003-2863-5772"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Jonathan Adam",
      "orcid": "0009-0001-9509-9503"
    },
    {
      "affs": [
        3,
        5
      ],
      "name": "Rui Wang-Sattler",
      "orcid": "0000-0002-8794-8229"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Karsten Suhre",
      "orcid": "0000-0001-9638-3912"
    },
    {
      "affs": [
        8,
        9,
        10
      ],
      "name": "Jerzy Adamski",
      "orcid": "0000-0001-9259-0199"
    },
    {
      "affs": [
        11
      ],
      "name": "Jutta Lintelmann"
    },
    {
      "affs": [
        12,
        13
      ],
      "name": "Sabrina Schlesinger"
    },
    {
      "affs": [
        11
      ],
      "name": "Alexander Cecil",
      "orcid": "0000-0002-1430-1790"
    },
    {
      "affs": [
        11,
        14
      ],
      "name": "Michael Witting"
    },
    {
      "affs": [
        15,
        16,
        17
      ],
      "name": "Wolfgang Koenig",
      "orcid": "0000-0002-2064-9603"
    },
    {
      "affs": [
        15,
        16
      ],
      "name": "Moritz Von Scheidt",
      "orcid": "0000-0001-7159-8271"
    },
    {
      "affs": [
        15,
        16
      ],
      "name": "Heribert Schunkert",
      "orcid": "0000-0001-6428-3001"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Annette Peters",
      "orcid": "0000-0001-6645-0985"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Harald Grallert"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Sapna Sharma",
      "orcid": "0000-0003-1039-8879"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0w4vta7n688t7.bib",
  "cited_by": 0,
  "doi": "10.3390/metabo16110821",
  "fulltext_url": null,
  "id": "0w4vta7n688t7",
  "issns": [
    "2218-1989"
  ],
  "landing_url": "https://www.mdpi.com/2218-1989/16/11/821",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Metabolomics and Mass Spectrometry Studies"
    ]
  ],
  "openalex": "W7224125157",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/0w4vta7n688t7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "10.3390/metabo16110821",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-1989/16/11/821"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Metabolomics and Mass Spectrometry Studies",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Integrative Multi-Omics Reveals Distinct Molecular Signatures of Metabolic Syndrome from KORA FF4 Study",
  "title_text": "Integrative Multi-Omics Reveals Distinct Molecular Signatures of Metabolic Syndrome from KORA FF4 Study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/0w4vta7n688t7",
  "venue": "Metabolites",
  "versions": []
}