{
  "abstract": "Glucocorticoids (GCs) are regulators of metabolism, yet how physiological GC exposure remodels adipose metabolism and its relationship with circulating biomarkers remains poorly understood. In a randomised cross-over study of individuals with primary adrenal insufficiency, near-physiological GC exposure was compared to withdrawal using integrated serum metabolomics, abdominal subcutaneous microdialysis metabolomics, and adipose tissue transcriptomics. GC exposure induced coordinated changes in adipose lipid and amino-acid metabolism. Pathway-level entropy analysis revealed GC-state-dependent transcriptional reorganisation, with concentrated organisation during exposure and diffuse organisation during withdrawal. Integrative hypergraph and topological analyses revealed GC-state-dependent reorganisation of circulating metabolite-adipose tissue relationships, with greater higher-order coordination during exposure. The circulating phenylalanine/kynurenine ratio discriminated GC state, showed the strongest shared connectivity to GC-regulated adipose networks, persisted at midnight and in an independent dose-response study, and exhibited circadian rhythmicity. These findings reveal dynamic GC regulation of adipose metabolism and identify a circulating biomarker with potential to guide personalised GC therapy.",
  "abstract_shown": true,
  "affiliations": [
    "The University of Manchester"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "K. Bennett"
    },
    {
      "name": "D. Chantzichristos"
    },
    {
      "name": "T. Garner"
    },
    {
      "name": "P.-A. Jansson"
    },
    {
      "name": "A. Meyer"
    },
    {
      "name": "E. Doman"
    },
    {
      "name": "J. McQueen"
    },
    {
      "name": "P.-A. Svensson"
    },
    {
      "name": "O. Ragnarsson"
    },
    {
      "name": "G. Johannsson"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Stevens"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3wfa2p0st1c1a.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.08.757658",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757658v1.full",
  "id": "3wfa2p0st1c1a",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757658v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "systems biology"
    ],
    [
      "openalex",
      "2712|Adrenal Hormones and Disorders"
    ]
  ],
  "openalex": "W7221076702",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757658v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3wfa2p0st1c1a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:49Z",
      "native_id": "10.64898/2026.10.08.757658",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757658v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:systems biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Higher-Order Organization Links Circulating Metabolites to Glucocorticoid Action in Human Adipose Tissue",
  "title_text": "Higher-Order Organization Links Circulating Metabolites to Glucocorticoid Action in Human Adipose Tissue",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:49Z",
  "url": "https://research.draconitic.com/paper/3wfa2p0st1c1a",
  "venue": "bioRxiv",
  "versions": []
}