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Peer-reviewedCC BYMedComm

Leptin Neutralization Attenuates Inflammaging in Endothelial and Immune Cell Models.

  • Valeria Pellegrini1
  • Rosalba La Grotta1
  • Alessia Metallo1
  • Francesca Carreras1
  • Chiara Frigé1
  • Giulia Matacchione2
  • Angelica Giuliani3
  • Jacopo Sabbatinelli2,4
  • Fabiola Olivieri2,5
  • Francesca Rispoli6
  • Lorenzo Drago6,7
  • Cesare Celeste Berra8
9 more authors
  • Raffaele Marfella9
  • Giuseppe Paolisso9,10
  • Giuseppe Matarese11,12
  • Claudio Procaccini12
  • Ilaria Spatocco11
  • Giorgia Mele11
  • Paola de Candia11
  • Antonio Ceriello1
  • Francesco Prattichizzo1
12 affiliations
  1. 1IRCCS MultiMedica Milan Italy.
  2. 2Clinic of Laboratory and Precision Medicine IRCCS INRCA Ancona Italy.
  3. 3Istituti Clinici Scientifici Maugeri IRCCS Cardiac Rehabilitation Unit of Bari Institute Bari Italy.
  4. 4Department of Clinical and Molecular Sciences (DISCLIMO) Università Politecnica delle Marche Ancona Italy.
  5. 5Advanced Technology Center For Aging Research IRCCS INRCA Ancona Italy.
  6. 6UOC Laboratory of Clinical Medicine With Specialized Areas IRCCS MultiMedica Milan Italy.
  7. 7Clinical Microbiology and Microbiome Laboratory Department of Biomedical Sciences For Health University of Milan Milan Italy.
  8. 8Department of Endocrinology IRCCS MultiMedica Milan Italy.
  9. 9Department of Advanced Medical and Surgical Sciences University of Campania "Luigi Vanvitelli" Naples Italy.
  10. 10UniCamillus International Medical University Rome Italy.
  11. 11Dipartimento Di Medicina Molecolare e Biotecnologie Mediche Università degli Studi di Napoli Federico II Naples Italy.
  12. 12Laboratorio Di Immunologia Istituto Degli Endotipi in Oncologia Metabolismo e Immunologia "G. Salvatore" Consiglio Nazionale delle Ricerche (IEOMI-CNR) Napoli Italy.
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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.

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Cite

BibTeXRIS
BibTeX
@article{pellegrini2026leptin,
  title = {{Leptin Neutralization Attenuates Inflammaging in Endothelial and Immune Cell Models.}},
  author = {Valeria Pellegrini and Rosalba La Grotta and Alessia Metallo and Francesca Carreras and Chiara Frigé and Giulia Matacchione and Angelica Giuliani and Jacopo Sabbatinelli and Fabiola Olivieri and Francesca Rispoli and Lorenzo Drago and Cesare Celeste Berra and Raffaele Marfella and Giuseppe Paolisso and Giuseppe Matarese and Claudio Procaccini and Ilaria Spatocco and Giorgia Mele and Paola de Candia and Antonio Ceriello and Francesco Prattichizzo},
  journal = {MedComm},
  year = {2026},
  month = oct,
  doi = {10.1002/mco2.71082},
  url = {https://europepmc.org/article/MED/42921584},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Leptin Neutralization Attenuates Inflammaging in Endothelial and Immune Cell Models.
AU  - Valeria Pellegrini
AU  - Rosalba La Grotta
AU  - Alessia Metallo
AU  - Francesca Carreras
AU  - Chiara Frigé
AU  - Giulia Matacchione
AU  - Angelica Giuliani
AU  - Jacopo Sabbatinelli
AU  - Fabiola Olivieri
AU  - Francesca Rispoli
AU  - Lorenzo Drago
AU  - Cesare Celeste Berra
AU  - Raffaele Marfella
AU  - Giuseppe Paolisso
AU  - Giuseppe Matarese
AU  - Claudio Procaccini
AU  - Ilaria Spatocco
AU  - Giorgia Mele
AU  - Paola de Candia
AU  - Antonio Ceriello
AU  - Francesco Prattichizzo
PY  - 2026
DA  - 2026/10/23
JO  - MedComm
DO  - 10.1002/mco2.71082
UR  - https://europepmc.org/article/MED/42921584
AB  - 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.
SN  - 2688-2663
ER  -