A1类清道夫受体在脂肪棕色化中的作用及其机制研究
DOI:
作者:
作者单位:

南京医科大学

作者简介:

通讯作者:

中图分类号:

基金项目:

国家自然科学基金项目(面上项目,重点项目,重大项目)


Studies on Class A1 Scavenger Receptor in Adipose Browning
Author:
Affiliation:

Nanjing Medical University

Fund Project:

The National natural Science Foundation of China(General Program,key Program,Major Research Plan)

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的:在寒冷刺激诱导下,探讨A1类清道夫受体(SR-A1)在脂肪棕色化进程中的作用及其机制。方法:qRT-PCR、Western blot和免疫组织化学检测正常饮食(CD)的野生型(WT)小鼠和SR-A1-/-(KO)小鼠给予寒冷刺激1、14、30 d后,皮下白色脂肪组织和棕色脂肪组织中SR-A1以及表征脂肪棕色化作用和程度指标(UCP1、Cidea、Cox8b)的表达。监测正常饮食和高脂饮食(HFD)12周的WT和KO小鼠体重变化,并使用代谢笼法监测小鼠耗氧量和产热量变化;qRT-PCR和免疫组织化学检测高脂饮食12周的WT和KO小鼠给予寒冷刺激7天后,小鼠皮下白色脂肪组织和棕色脂肪组织中UCP1、Cidea、Cox8b表达。qRT-PCR和流式细胞术检测正常饮食的WT和KO小鼠给予寒冷刺激30天后,小鼠皮下白色脂肪组织中巨噬细胞数量变化以及M1型和M2型巨噬细胞的极化情况。体外实验应用巨噬细胞条件培养基处理小鼠前脂肪细胞,qRT-PCR检测成熟脂肪细胞的棕色化程度。结果:慢性寒冷刺激下,与WT CD小鼠相比,KO CD小鼠脂肪棕色化程度明显降低。高脂饮食喂养12周后,小鼠体重明显增加。与WT HFD小鼠相比,KO HFD小鼠体重增加更加明显,耗氧量和产热量明显降低;寒冷刺激下,与WT HFD小鼠相比,KO HFD小鼠脂肪棕色化程度明显降低。寒冷刺激下,KO CD小鼠皮下白色脂肪组织中巨噬细胞数量明显增加,M1型巨噬细胞比例明显升高,M2型巨噬细胞比例明显降低。体外细胞研究发现,与WT小鼠腹腔巨噬细胞条件培养基诱导的成熟脂肪细胞相比,KO小鼠腹腔巨噬细胞条件培养基诱导的成熟脂肪细胞棕色化程度明显降低。结论:寒冷刺激下,SR-A1可以促进小鼠皮下白色脂肪组织和棕色脂肪组织产热,并且这一过程是通过M2型巨噬细胞的极化反应得以实现。

    Abstract:

    Objective: This study aims to investigate the role and mechanism of Class A1 scavenger receptor (SR-A1) in Adipose Browning induced by cold exposure. Methods: The expression of SR-A1, UCP1, Cidea and Cox8b in white adipose tissue and brown adipose tissue of wild type (WT) mice and SR-A1-/- (KO) mice fed common diet (CD) were detected by qRT-PCR, western blot and immunohistochemistry after 1, 14, and 30 days of cold exposure. The weight changes were monitored in WT and KO mice on normal and high fat diets for 16 weeks. The metabolic cage method was used to monitor the changes of O2 Consumption and heat production. The expression of UCP1, Cidea and Cox8b in white adipose tissue and brown adipose tissue of WT and KO mice fed high fat diet (HFD) for 16 weeks was detected by qRT-PCR and immunohistochemistry after 7 days of cold exposure. The number of macrophages and polarization of M1-type and M2-type macrophages in white adipose tissue of WT and KO mice after 30 days of cold exposure were detected by qRT-PCR and flow cytometry. Mouse preadipocytes were treated with macrophage conditioned medium in vitro, and the degree of Browning of mature adipocytes was detected by qRT-PCR. Results: Compared with WT CD mice, the browning of adipose induced by chronic cold exposure was significantly reduced in KO CD mice. When we exposed mice to HFD for 16 weeks, the weight of mice increased significantly. Compared with WT HFD mice, KO HFD mice had significantly higher weight, lower O2 Consumption and heat production. The Adipose Browning in KO HFD mice was significantly reduced compared with WT HFD mice after cold exposure, and the number of macrophages in subcutaneous white adipose tissue of KO CD mice increased significantly, the proportion of M1 macrophages increased significantly, the proportion of M2 macrophages decreased significantly. Compared with the mature adipocytes induced by peritoneal macrophage conditioned medium in WT mice, the Browning degree of mature adipocytes induced by peritoneal macrophage conditioned medium in KO mice was significantly reduced. Conclusion: Under cold exposure, SR-A1 promoted the Browning of white adipose tissue and brown adipose tissue subcutaneously in mice, and this effect was realized through the polarization of M2-type macrophages.

    参考文献
    相似文献
    引证文献
引用本文
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2023-04-26
  • 最后修改日期:2023-07-16
  • 录用日期:2023-10-18
  • 在线发布日期:
  • 出版日期: