{
  "abstract": "Cardiometabolic heart failure with preserved ejection fraction (HFpEF) is a heterogenous metabolic disease, which in the heart presents as left ventricle diastolic dysfunction, ventricular stiffness, and myocardial structural remodeling. Deleterious changes in cardiac metabolism are central to HFpEF pathophysiology, and proposed treatments for the disease have focused on repairing these defects. In this study, we used a preclinical mouse model that recapitulates cardiometabolic HFpEF to elucidate the molecular mechanisms driving cardiac dysfunction, and tested whether recombinant Adropin (a liver- and brain-derived endogenous peptide hormone) could reverse observed defects. We show that long-term treatment with Adropin reversed multiple markers of HFpEF-related cardiac dysfunction (including fibrosis, diastolic dysfunction, and cardiomyocyte hypertrophy). Using untargeted metabolomics, we found that Adropin treatment reduced hexosamine biosynthesis pathway activity, leading to a reduction in the O-GlcNAcylation of the cardiac fatty acid oxidation enzyme long chain acyl-CoA dehydrogenase (LCAD). Reducing LCAD O-GlcNAcylation increased LCAD activity in vitro , and reduced the accumulation of long-chain acylcarnitines in HFpEF mouse hearts in vivo. Our results suggest that Adropin may restore cardiac metabolic function in HFpEF, and that targeting this pathway may be a novel therapeutic avenue for this disease. CLINICAL PERSPECTIVE - Adropin is a circulating liver- and brain-derived peptide that regulates energy metabolism in the heart and other high metabolic-demand tissues. The plasma abundance of Adropin is decreased in diabetic, hypertensive, and aged individuals; all comorbid risk factors for the development of heart failure with preserved ejection (HFpEF). We therefore examined the potential role of Adropin in HFpEF pathophysiology. - Patients with HFpEF display significant reductions in circulating Adropin levels, matching those seen in comorbid diseases. In a mouse model of HFpEF, treatment with recombinant Adropin reduced diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy. - These data suggest that targeting the Adropin pathway may represent a new therapeutic approach in HFpEF.",
  "abstract_shown": true,
  "affiliations": [
    "Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261",
    "Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261",
    "Division of Cardiology, University of Pittsburgh, Pittsburgh, PA 15261",
    "Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, PA 15261",
    "Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA 15261",
    "Division of Classical Hematology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261",
    "Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261",
    "Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15261"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
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        1,
        2
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      "name": "Bellina A.S. Mushala"
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        1,
        2
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      "name": "Michael W. Stoner"
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    {
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        1,
        2
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      "name": "Maryam Sharifi-Sanjani"
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        2
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      "name": "Janet R. Manning"
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    {
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        1,
        2
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      "name": "Paramesha Bugga"
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    {
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        1,
        2
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      "name": "Nisha Bhattarai"
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    {
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      "name": "Brenda McMahon"
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        3
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      "name": "Amber Vandevender"
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    {
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        4
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      "name": "Steven J. Mullet"
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    {
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        2
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      "name": "Brett A. Kaufman"
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        5
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      "name": "Sruti S. Shiva"
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    {
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        6
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      "name": "Cheng Zhang"
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    {
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        7
      ],
      "name": "Eric S. Goetzman"
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    {
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        2
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      "name": "Stephen Y. Chan"
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    {
      "affs": [
        6,
        4
      ],
      "name": "Stacy L. Gelhaus"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Michael J. Jurczak"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Iain Scott"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a9sbdmzyde9vw.bib",
  "cited_by": 7,
  "doi": "10.1042/cs20261501",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735424/",
  "id": "a9sbdmzyde9vw",
  "issns": [
    "0143-5221",
    "1470-8736"
  ],
  "landing_url": "https://doi.org/10.1042/cs20261501",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
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      "openalex",
      "2705|Cardiac Fibrosis and Remodeling"
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  "pdf_url": null,
  "pmcid": "PMC13735424",
  "pmid": "42275197",
  "published": "2026-07-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a9sbdmzyde9vw.ris",
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    {
      "first_seen": "2026-11-09T12:21:06Z",
      "native_id": "PMC13735424",
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      "url": "https://doi.org/10.1042/cs20261501"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Cardiac Fibrosis and Remodeling",
      "subfield": "cardiovascular"
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  ],
  "title": "Adropin protects against cardiac remodeling and metabolic dysfunction in a male mouse HFpEF model",
  "title_text": "Adropin protects against cardiac remodeling and metabolic dysfunction in a male mouse HFpEF model",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:06Z",
  "url": "https://research.draconitic.com/paper/a9sbdmzyde9vw",
  "venue": "Clinical science (London, England : 1979)",
  "versions": []
}