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We sought to define how NR4A1 governs early adipogenesis and adipose tissue plasticity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Doxycycline\u2010inducible NR4A1\u2010overexpressing and NR4A1\u2010deficient 3T3\u2010L1 models were used to assess lipid accumulation, mitotic clonal expansion (MCE), and cell\u2010cycle dynamics. Multiomics integration (RNA\u2010seq and chromatin assays) identified NR4A1 targets. The functionality of two lead candidates, ANLN and CDC20, was tested by genetic knockdown and pharmacological inhibition. Diet\u2010induced obese mice received the NR4A1 antagonist C\u2010DIM8 alone or combined with the PPAR\u03b3 agonist rosiglitazone to evaluate adipose expansion and metabolic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      NR4A1 exerted a stage\u2010specific inhibitory effect during early differentiation, reducing expression of canonical adipogenic markers and lipid accumulation. Integrative transcriptomic and chromatin analyses identified\n                      <jats:italic>Anln<\/jats:italic>\n                      and\n                      <jats:italic>Cdc20<\/jats:italic>\n                      as direct NR4A1 targets essential for MCE. Depletion of either gene phenocopied NR4A1 overexpression, inducing G2\/M arrest and blunting of adipogenesis. Pharmacological CDC20 inhibition with Apcin suppressed preadipocyte proliferation and differentiation in a dose\u2010dependent manner. Importantly, in a diet\u2010induced obese mouse model, combined treatment with the NR4A1 antagonist C\u2010DIM8 and the PPAR\u03b3 agonist rosiglitazone promoted AP proliferation, hyperplastic adipose tissue expansion, and improved glucose tolerance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      NR4A1 functions as a transcriptional gatekeeper of adipogenic initiation by restraining the\n                      <jats:italic>Anln<\/jats:italic>\n                      \/\n                      <jats:italic>Cdc20<\/jats:italic>\n                      cell\u2010cycle program. Pharmacological modulation of the NR4A1\u2013cell\u2010cycle axis, particularly alongside PPAR\u03b3 activation, may offer a strategy to augment adipose tissue plasticity and metabolic resilience in obesity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70655","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:00:36Z","timestamp":1791007236000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of the NR4A1\u2010mediated cell cycle checkpoint enhances hyperplastic adipogenesis and glucose homeostasis in obesity"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7105-9024","authenticated-orcid":false,"given":"Wanning","family":"Qiao","sequence":"first","affiliation":[{"name":"School of Public Health (Shenzhen) Sun Yat\u2010sen University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6709-3501","authenticated-orcid":false,"given":"Cun","family":"Ku","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen) Sun Yat\u2010sen University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8821-848X","authenticated-orcid":false,"given":"G. 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