| 高璐琪,司原成,康朝霞,王显云,李志菊.基于DNA甲基化技术探讨营养型肥胖小鼠脂肪细胞表观遗传的作用机制[J].,2024,(7):1228-1234 |
| 基于DNA甲基化技术探讨营养型肥胖小鼠脂肪细胞表观遗传的作用机制 |
| Based on DNA Methylation Technology to Explore the Mechanism of Action of Epigenetic Inheritance in Adipocytes of Nutritionally Obese Mice |
| 投稿时间：2023-09-26 修订日期：2023-11-04 |
| DOI：10.13241/j.cnki.pmb.2024.07.005 |
| 中文关键词: 高脂饮食 营养型肥胖 DNA甲基化 小鼠 作用机制 |
| 英文关键词: High-fat diet Nutritional obesity DNA methylation Mice Mechanism of action |
| 基金项目:国家自然科学基金项目（82260853）；贵州省基础研究（科学技术基金）项目（黔科合基础-ZK[2022]一般484）；贵州省卫生健康委科学技术基金项目（gzwkj2022-005） |
|
| 摘要点击次数: 320 |
| 全文下载次数: 233 |
| 中文摘要: |
| 摘要 目的：营养型肥胖症的作用机制较为复杂，课题组从表观遗传的角度，探究营养型肥胖鼠脂肪细胞DNA甲基化的差异变化，从新的角度研究肥胖症产生与进展的作用机制。方法：选用SPF级C57BL/6小鼠，采用高脂饮食诱导肥胖模型，喂养8周后，将达到营养型肥胖标准的小鼠设为肥胖组（M）；定期记录小鼠的体重；通过HE染色观察脂肪组织形态、ELISA检测血清中TC、TG、HDL-C和LDL-C的差异，并采用MethylRAD-seq技术检测肾周脂肪组织细胞DNA甲基化差异表达的位点与基因。结果：正常组（N）相比较，肥胖组的小鼠体重和肾周脂肪的重量明显增加（P＜0.01），肾周脂肪细胞形态发生改变，同视野下脂肪细胞数目明显变少，直径明显变大（P＜0.01）；肥胖组的TC显著升高（P＜0.01），TG显著降低（P＜0.01）。经MethylRAD-seq技术，筛查出N组和M组实验鼠中差异显著的甲基化位点共有5528个，其中上调位点3003个和下调位点2525个；DNA甲基化基因表达存在显著差异的有80个，包括表达上调44个基因和下调36个基因；GO/KEGG的富集分析显示，两组实验鼠DNA 甲基化的作用机制涉及多种生物过程、分子功能以及信号通路的调控。结论：高脂饮食诱导的营养型肥胖小鼠脂肪细胞存在表观遗传的差异变化，肥胖鼠肾周脂肪组织细胞中的基因表达及DNA甲基化有明显差异，可以在分子及基因水平上，为肥胖症及其相关疾病的发生机制提供新的研究方向。 |
| 英文摘要: |
| ABSTRACT Objective: The mechanism of action of nutritional obesity is more complex. The group explored the differential changes of DNA methylation in adipocytes of nutritionally obese mice from the perspective of epigenetic, to study the mechanism of obesity generation and progression from a new angle. Methods: SPF grade C57BL/6 mice were selected to establish a high-fat diet-induced obesity model. The mice were fed a high-fat chow for 8 weeks, and those that reached the criteria for nutritional obesity were assigned to the obese group (M). The body weights of the mice were regularly recorded. The morphology of adipose tissues was observed using HE staining. Differences in serum TC, TG, HDL-C, and LDL-C were examined using ELISA. The differences in DNA methylation of the adipocytes were analyzed using MethylRAD-seq technology to identify loci and genes with differentially expressed DNA methylation in perirenal adipose tissue cells. Results: TCompared with the normal group (N), mice in the obese group had significantly increased body weight and perirenal fat weight(P<0.01). Additionally, the morphology of perirenal adipocytes was altered, with a significantly lower number of adipocytes in the same field of view and a significantly larger diameter (P<0.01). The obese group also exhibited significantly higher TC levels (P<0.01), while TG levels were significantly lower (P<0.01). By MethylRAD-seq technology, a total of 5528 methylation sites with significant differences were identified in experimental rats from group N and group M. Among these sites, 3003 were up-regulated and 2525 were down-regulated. Additionally, 80 DNA methylation genes showed significant differences in their expression, with 44 genes being up-regulated and 36 genes being down-regulated. The GO/KEGG enrichment analysis revealed that the DNA methylation mechanism in the two groups of experimental rats is involved in various biological processes, molecular functions, and regulation of signaling pathways. Conclusion: A Epigenetic differential changes occur in adipocytes of nutritionally obese mice induced by a high-fat diet. Additionally, there are significant differences in gene expression and DNA methylation in perirenal adipose tissue cells of obese mice. These findings provide a new research direction for understanding the molecular and genetic mechanisms underlying the occurrence of obesity and its related diseases. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |
