{
  "abstract": "Diet-induced obesity (DIO), modeled by a high-fat diet (HFD), adversely affects circadian glucose homeostasis partly by dysregulating fasting/feeding cycles. However, its impact on circadian {beta}-cell function and relevant transcriptional programs remains unclear. To investigate this, we exposed male and female C57BL/6 mice to either chow or HFD for eight weeks and assessed behavioral (feeding/activity), physiological (glucose tolerance/insulin secretion), transcriptomic (RNA sequencing (RNA-seq)), and epigenomic (Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-seq)) circadian rhythms. Additionally, we tested whether normalizing fasting/feeding cycles via time-restricted feeding (tRF) during the dark- or light-phase of the circadian cycle could mitigate DIO's deleterious effects. DIO disrupted circadian fasting/feeding rhythms, with greater disruption in males than females (p<0.05 vs. CHOW). In males, DIO abolished circadian regulation of glucose tolerance and in vivo glucose-stimulated insulin secretion (GSIS) (p<0.05 vs. chow), whereas female mice maintained circadian glucose homeostasis. RNA-seq analysis of male islets revealed a 42.1% reduction in circadian-regulated transcripts under DIO, with weakened rhythms in key {beta}-cell pathways such as insulin secretion. Moreover, ATAC-Seq analysis indicated reduced chromatin accessibility of genes/pathways related to insulin secretion and glucose hemostasis under DIO (p<0.05 vs. chow) during both dark- or light-phase of the circadian cycle. Notably, dark-phase time-restricted feeding (tRF) restored circadian glucose tolerance, GSIS, and islet gene expression, whereas light-phase tRF enhanced {beta}-cell function during the normally inactive/light phase of the circadian cycle, further suppressing circadian rhythmicity of the islet transcriptome. Motif analysis indicated that DIO suppressed the activity of D-box transcription factors (TFs) (DBP and TEF) while enhancing the activity of ETS family TFs (ELK1, ETS2, ELF2, and GABPA), which was partly mitigated by dark-phase tRF. Our study demonstrates that DIO disrupts circadian {beta}-cell function and gene expression by dysregulating fasting/feeding cycles in male mice and reveals significant sex differences in how DIO affects circadian glucose homeostasis and {beta}-cell function.",
  "abstract_shown": true,
  "affiliations": [
    "Mayo Clinic"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "L. Zhang"
    },
    {
      "name": "S. K. Sen"
    },
    {
      "name": "K. Rakshit"
    },
    {
      "name": "T. Nguyen"
    },
    {
      "name": "K. Omori"
    },
    {
      "name": "A. Bharath"
    },
    {
      "name": "Z. Wei"
    },
    {
      "name": "A. Gaspar-Maia"
    },
    {
      "affs": [
        0
      ],
      "name": "A. V. Matveyenko"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5j9vnvgd2ggq8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.02.763239",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763239v1.full",
  "id": "5j9vnvgd2ggq8",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763239v1",
  "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",
      "physiology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763239v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5j9vnvgd2ggq8.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T00:21:33Z",
      "native_id": "10.64898/2026.11.02.763239",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763239v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:physiology",
      "subfield": "physiology"
    }
  ],
  "title": "Circadian feeding rhythm loss drives sex-specific β-cell dysfunction in diet-induced obesity",
  "title_text": "Circadian feeding rhythm loss drives sex-specific β-cell dysfunction in diet-induced obesity",
  "type": "preprint",
  "updated_at": "2026-11-05T00:20:56Z",
  "url": "https://research.draconitic.com/paper/5j9vnvgd2ggq8",
  "venue": "bioRxiv",
  "versions": []
}