{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:03:21Z","timestamp":1784783001042,"version":"3.55.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Gastroenterol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The incidence of ulcerative colitis (UC) and obesity has risen in recent years, potentially linked through metabolic dysregulation and chronic inflammation. The nuclear receptor NR1D1 is pivotal in regulating circadian rhythms and plays a significant role in inflammation and metabolism. This study investigates the therapeutic effects and mechanisms of the NR1D1 agonist SR9009 on obesity-related UC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established a mouse model of obesity-induced UC utilizing a high-fat diet alongside dextran sulfate sodium (DSS). 32 male C57BL\/6 mice were divided into four groups: control (DZ), high-fat diet (GZ), obesity associated UC model group (UC), and SR9009 intervention group (JD), with eight mice each. We evaluated body weight, blood lipids, colonic tissue alterations, IL-1\u03b2, IL-18, macrophage polarization, and NR1D1 expression levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mice in the UC group demonstrated significantly elevated body weight, spleen index, TG, CHOL and inflammatory markers (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.01). Pathological scores of colonic tissues increased markedly (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001), with a rise in M1 macrophages (CD68\n                      <jats:sup>+<\/jats:sup>\n                      ) and a decline in M2 macrophages (CD206\n                      <jats:sup>+<\/jats:sup>\n                      ) (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). NR1D1 expression was notably downregulated (P&amp;lt;0.01). Post-SR9009 intervention, the JD group showed significantly reduced serum TG and CHOL levels (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001, 0.011), IL-1\u03b2 and IL-18 (P&amp;lt;0.001), improved colonic pathology (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001), a decrease in M1 macrophages, an increase in M2 macrophages, and an enhanced M1\/M2 ratio (P&amp;lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SR9009 mitigates intestinal inflammation in obesity associated UC by activating NR1D1, potentially modulating NF-\u03baB-related signaling, and modulating macrophage polarization (suppressing M1 and enhancing M2). These findings propose a novel strategy for targeting NR1D1 in the treatment of obesity-related ulcerative colitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgstr.2026.1762028","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:32:30Z","timestamp":1784781150000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SR9009 regulates macrophage polarization via the NR1D1\/NF-\u03baB axis to ameliorate obesity-associated ulcerative colitis"],"prefix":"10.3389","volume":"5","author":[{"given":"Zhixue","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of General Surgery, Beijing Jishuitan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Beijing Jishuitan Hospital, Capital 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