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Functional decline of adipocyte precursor cells (APCs) and accumulation of senescent cells in the subcutaneous adipose tissue contributes to the progression toward T2D. LncRNAs regulate cell senescence and may be implicated in determining this abnormality in APCs. Here, we report that APCs from individuals with obesity show a gradual increase in multiple senescence markers, which worsens in parallel with the progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) or T2D. Transcriptomic analysis identified\n                    <jats:italic>PANDAR<\/jats:italic>\n                    as the top\u2010ranked lncRNA differentially expressed in APCs from individuals with obesity and T2D and non\u2010obese subjects. Q\u2010PCR confirmed\n                    <jats:italic>PANDAR<\/jats:italic>\n                    up\u2010regulation in APCs from individuals with obesity, at progressively increased levels in those who developed, respectively, IGT and T2D. Bisulfite sequencing and luciferase assays revealed that, in parallel with glucose tolerance deterioration, the \u22121317 CpG at the\n                    <jats:italic>PANDAR<\/jats:italic>\n                    promoter became hypo\u2010methylated in obesity, resulting in enhanced\n                    <jats:italic>PANDAR<\/jats:italic>\n                    induction by p53.\n                    <jats:italic>PANDAR<\/jats:italic>\n                    silencing in senescent APCs from individuals with obesity and T2D caused repression of senescence programs and cell cycle re\u2010entry.\n                    <jats:italic>PANDAR<\/jats:italic>\n                    transcription in white blood cells (WBCs) mirrored that in APCs. Also, individuals with obesity exhibited rescue of\n                    <jats:italic>PANDAR<\/jats:italic>\n                    transcription in WBCs following bariatric surgery, accompanied by enhanced methylation at the regulatory\n                    <jats:italic>PANDAR<\/jats:italic>\n                    \u22121317 CpG. In conclusion,\n                    <jats:italic>PANDAR<\/jats:italic>\n                    dysregulation is a newly identified mechanism determining the early senescence of APCs from individuals with obesity, which worsens along the progression toward T2D. In the future,\n                    <jats:italic>PANDAR<\/jats:italic>\n                    targeting may represent a valuable strategy to delay this progression.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401470r","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T11:05:43Z","timestamp":1728299143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hypomethylation at\n                    <scp>\n                      <i>PANDAR<\/i>\n                    <\/scp>\n                    promoter progressively induces senescence in adipocyte precursor cells in subjects with obesity and type 2 diabetes"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3510-7663","authenticated-orcid":false,"given":"Antonella","family":"Desiderio","sequence":"first","affiliation":[{"name":"Department of Translational Medicine Federico II University of Naples  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