肥胖期间脂肪组织炎症的LXR调节与失调的巨细胞功能有关
Jessica Aparecida da Silva Pereira1,2,3, Gerson Profeta de Souza4,5, João V Virgilio-da-Silva1,2
1Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, State University of Campinas Institute of Biology, Campinas, Brazil.
Obesity (Silver Spring, Md.)
|December 5, 2024
概括
肝脏X受体 (LXRs) 调节肥胖症中的炎症. 缺乏LXRβ会使脂肪组织炎症恶化,而通过调节巨细胞功能来降低宁素 (NAR) 治疗,从而为胰岛素抵抗提供治疗潜力.
科学领域:
- 代谢性疾病研究研究.
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
背景情况:
- 肝X受体 (LXRs) 是胆固醇代谢和免疫反应的关键调节者.
- 肥胖相关的炎症包括胆固醇水平升高和脂肪组织巨细胞 (ATM) 现型变化.
- 在肥胖相关的脂肪组织炎症和胰岛素抵抗中,LXR异型的特定作用仍然不完全理解.
研究的目的:
- 阐明LXR异型 (LXRα和LXRβ) 在饮食诱导的肥胖相关的脂肪组织炎症和胰岛素抵抗中的不同作用.
- 在肥胖,抗胰岛素模型中研究使用纳林根因 (NAR) 的LXR调制的治疗潜力.
主要方法:
- 在体内研究中,使用NAR治疗肥胖小鼠,评估胰岛素敏感性和脂肪组织炎症.
- 在体内研究中还使用了LXRα,LXRβ和组合LXRαβ淘汰赛小鼠来评估LXR缺乏效应.
- 在体外研究中使用了野生型和LXR淘汰赛小鼠的骨髓衍生的巨细胞,用脂多糖 (LPS) 刺激,以评估NAR对巨细胞功能和新陈代谢的影响.
主要成果:
- 删除LXR以LXRβ依赖的方式加剧了脂肪组织炎症,增加了促炎性ATM标志物.
- 纳灵宁 (NAR) 被确定为巨细胞中的LXR激动剂,减少促炎性细胞因子分泌.
- 在肥胖小鼠中,NAR治疗减少了脂肪组织炎症,ATM透和单细胞存在,改善了代谢参数.
结论:
- 独特的LXR异型在调节脂肪组织炎症方面发挥着特定的作用.
- 在脂肪组织巨细胞中,LXRβ对于维持抗炎和促炎反应之间的平衡至关重要.
- 准LXRβ是一种有前途的治疗策略,用于治疗脂肪组织炎症和相关的胰岛素抵抗.
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