SR9009 regulates macrophage polarization via the NR1D1/NF-κB axis to ameliorate obesity-associated ulcerative colitis

Abstract Objective 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. Methods 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-1β, IL-18, macrophage polarization, and NR1D1 expression levels. Results Mice in the UC group demonstrated significantly elevated body weight, spleen index, TG, CHOL and inflammatory markers ( P