{
  "abstract": "Leptin, a proinflammatory adipokine, contributes to the chronic low-grade inflammation seen in obesity, but its role in age-related inflammation, that is inflammaging, has been poorly studied. We thus tested the effect of blocking leptin receptor (LEP-R) binding in five models of inflammaging, that is replicative senescent endothelial cells, hyperglycemia-treated macrophages or endothelial cells, lipopolysaccharide (LPS)-exposed macrophages, and TCR-stimulated CD4+ T cells. In endothelial cells, leptin enhanced senescence, while leptin neutralization suppressed the senescence-associated secretory phenotype, two effects mediated in part by the mTOR pathway. In both macrophages and endothelial cells, leptin blockade blunted hyperglycemia-induced inflammation, while in macrophages, it also suppressed the LPS-induced senescent and proinflammatory phenotype. In T cells, leptin neutralization produced divergent effects, attenuating the expression of inflammatory and senescence markers in conventional T cells but not in regulatory T cells. To assess translational relevance, we measured leptin and inflammaging markers in plasma samples from two independent cohorts, one of healthy individuals (n = 121) and another of people with Type 2 diabetes (n = 93). In healthy subjects, leptin levels were higher in people with hs-CRP ≥ 3 mg/dL compared with those below such threshold, also after adjustment for BMI. Leptin levels showed BMI-adjusted positive correlations with IL-6 and hs-CRP in healthy individuals and with hs-CRP and IL-8 in people with diabetes. These findings suggest that leptin might fuel inflammaging and that its neutralization exerts anti-inflammatory effects across multiple, related models.",
  "abstract_shown": true,
  "affiliations": [
    "IRCCS MultiMedica Milan Italy.",
    "Clinic of Laboratory and Precision Medicine IRCCS INRCA Ancona Italy.",
    "Istituti Clinici Scientifici Maugeri IRCCS Cardiac Rehabilitation Unit of Bari Institute Bari Italy.",
    "Department of Clinical and Molecular Sciences (DISCLIMO) Università Politecnica delle Marche Ancona Italy.",
    "Advanced Technology Center For Aging Research IRCCS INRCA Ancona Italy.",
    "UOC Laboratory of Clinical Medicine With Specialized Areas IRCCS MultiMedica Milan Italy.",
    "Clinical Microbiology and Microbiome Laboratory Department of Biomedical Sciences For Health University of Milan Milan Italy.",
    "Department of Endocrinology IRCCS MultiMedica Milan Italy.",
    "Department of Advanced Medical and Surgical Sciences University of Campania \"Luigi Vanvitelli\" Naples Italy.",
    "UniCamillus International Medical University Rome Italy.",
    "Dipartimento Di Medicina Molecolare e Biotecnologie Mediche Università degli Studi di Napoli Federico II Naples Italy.",
    "Laboratorio Di Immunologia Istituto Degli Endotipi in Oncologia Metabolismo e Immunologia \"G. Salvatore\" Consiglio Nazionale delle Ricerche (IEOMI-CNR) Napoli Italy."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Valeria Pellegrini"
    },
    {
      "affs": [
        0
      ],
      "name": "Rosalba La Grotta"
    },
    {
      "affs": [
        0
      ],
      "name": "Alessia Metallo"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesca Carreras",
      "orcid": "0000-0002-2959-2658"
    },
    {
      "affs": [
        0
      ],
      "name": "Chiara Frigé"
    },
    {
      "affs": [
        1
      ],
      "name": "Giulia Matacchione"
    },
    {
      "affs": [
        2
      ],
      "name": "Angelica Giuliani"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Jacopo Sabbatinelli"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Fabiola Olivieri"
    },
    {
      "affs": [
        5
      ],
      "name": "Francesca Rispoli"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Lorenzo Drago"
    },
    {
      "affs": [
        7
      ],
      "name": "Cesare Celeste Berra"
    },
    {
      "affs": [
        8
      ],
      "name": "Raffaele Marfella"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Giuseppe Paolisso"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Giuseppe Matarese"
    },
    {
      "affs": [
        11
      ],
      "name": "Claudio Procaccini"
    },
    {
      "affs": [
        10
      ],
      "name": "Ilaria Spatocco"
    },
    {
      "affs": [
        10
      ],
      "name": "Giorgia Mele"
    },
    {
      "affs": [
        10
      ],
      "name": "Paola de Candia"
    },
    {
      "affs": [
        0
      ],
      "name": "Antonio Ceriello"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesco Prattichizzo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6369bef15htrc.bib",
  "cited_by": 0,
  "doi": "10.1002/mco2.71082",
  "fulltext_url": "https://europepmc.org/articles/PMC13693919",
  "id": "6369bef15htrc",
  "issns": [
    "2688-2663"
  ],
  "landing_url": "https://europepmc.org/article/MED/42921584",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Adipokines, Inflammation, and Metabolic Diseases"
    ]
  ],
  "openalex": "W7223344915",
  "pdf_url": "https://europepmc.org/articles/PMC13693919?pdf=render",
  "pmcid": "PMC13693919",
  "pmid": "42921584",
  "published": "2026-10-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6369bef15htrc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42921584",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42921584"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Adipokines, Inflammation, and Metabolic Diseases",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Leptin Neutralization Attenuates Inflammaging in Endothelial and Immune Cell Models.",
  "title_text": "Leptin Neutralization Attenuates Inflammaging in Endothelial and Immune Cell Models.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/6369bef15htrc",
  "venue": "MedComm",
  "versions": []
}