LDLR基因敲除小鼠皮下腹股沟脂肪基因表达谱研究

Study on gene expression profile of subcutaneous inguinal white adipose in LDLR knockout mice

目的探究LDLR基因敲除(LDLR^-/-)小鼠皮下腹股沟脂肪基因表达谱的变化及差异基因涉及的生物过程和信号通路。方法采用高脂饲料喂养LDLR基因敲除小鼠的肥胖模型,利用基因芯片技术分析正常C57BL/6J小鼠与肥胖模型小鼠皮下腹股沟脂肪组织中基因表达谱的差异及差异基因涉及的信号通路。结果与正常C57BL/6J小鼠比较,LDLR基因敲除小鼠皮下腹股沟脂肪组织中差异表达基因有602个,其中上调基因有394个,下调基因308个。GO富集和Pathways分析结果显示,这些差异基因的生物过程主要有炎症反应、免疫系统过程、及T细胞增殖的正向调控;信号通路主要有B细胞受体信号通路、自然杀伤细胞介导的细胞毒性、Toll样受体信号通路和趋化因子信号通路。结论B细胞受体信号通路、自然杀伤细胞介导的细胞毒性、Toll样受体信号通路和趋化因子信号通路中的差异基因可能涉及肥胖发病的机制,为肥胖及相关代谢疾病药物的研发提供依据。

Objective To explore the changes of gene expression profile and the biological processes and signal pathways involved in different genes of subcutaneous inguinal fat in LDLR knock out(LDLR^-/-)mice.Methods The obesity model of LDLR knockout mice was fed with high fat diet.The difference of gene expression profiles and the signaling pathways involved in different genes in subcutaneous inguinal adipose tissue between normal C57BL/6J mice and obese mice were analyzed by gene chip technology.Results Compared with normal C57BL/6J mice,there were 602 differentially expressed genes in subcutaneous inguinal adipose tissue of LDLR knockout mice.There were 394 up-regulated genes and 308 down-regulated genes.GO enrichment and Pathways analysis showed that the main biological processes of these differentially expressed genes were inflammatory response,immune system process and positive regulation of T cell proliferation.The signaling pathways include B cell receptor signaling pathway,natural killer cell mediated cytotoxicity,Toll-like receptor signaling pathway and chemokine signaling pathway.Conclusion Differential genes in B cell receptor signaling pathway,natural killer cell mediated cytotoxicity,Toll-like receptor signaling pathway and chemokine signaling pathway may be involved in the pathogenesis of obesity,which provides a basis for the research and development of drugs for obesity and related metabolic diseases.