LRP16基因对脂肪细胞能量代谢相关基因表达的影响

发布时间：2018-05-29 03:15

本文选题：脂细胞 + LRP16　；参考：《中国人民解放军军医进修学院》2009年硕士论文

【摘要】： LRP16是从健康成人外周血淋巴细胞中克隆的人类基因,它在多种雌激素依赖性肿瘤中高表达。近年肿瘤组织的代谢成为研究热点,一些促癌基因,并不一定起着促进增殖、抑制凋亡的作用,它们可能通过改变肿瘤组织的代谢模式使其适应乏氧、缺少营养物质供给的环境,从而生存下去。这提示我们,促癌基因也有可能影响机体的代谢模式——目前也已有这方面的证据。另外已经证实,一些肥胖调节基因在肿瘤发生方面起着一定的作用。因此我们假设肿瘤和肥胖可能存在“共同起源”,即某些基因的过度激活(或抑制)可能会导致同时发生肿瘤和肥胖。LRP16作为与雌激素作用相关的促癌基因,很可能在机体的营养物质代谢方面也扮演一定的角色。所以本课题希望在细胞层面上证明LRP16对脂肪细胞分化、胰岛素抵抗等方面有影响。本研究共分为3部分: 一:应用基因芯片技术研究LRP16基因对成熟脂肪细胞功能影响目的:探讨LRP16基因对成熟脂肪细胞功能影响及其潜在的临床意义。方法:(1)经典脂肪细胞诱导方案诱导前脂肪细胞为成熟脂肪细胞。(2)应用高通量基因芯片分析技术,通过比较高表达LRP16的成熟脂肪细胞与正常表达组差异表达的基因,分析LRP16可能涉及的信号通路和靶基因,为进一步研究确立方向。结果:实验组与对照组间差异表达基因共有1222个,其中653个上调,569个下调。其中涉及多个与脂肪分化、胰岛素抵抗以及糖脂代谢相关的信号通路。结论:对脂肪细胞而言,LRP16总体的功能是促进(微)炎症状态,对脂肪分化、胰岛素抵抗以及糖脂代谢都有影响。二:LRPl6基因可能通过促进PGC-1α的表达增强细胞的能量代谢目的与方法:通过质粒转染使3T3-L1脂肪细胞过表达LRP16(3T3-16)。通过油红O染色,在显微镜下观察LRP16对脂肪细胞脂滴形成的影响。使用Real-time PCR技术检测3T3-16与3T3-3.1(对照组)两组脂肪细胞与产热有关的基因mRNA的相对表达量。结果:脂肪细胞诱导成熟后,使用油红O染色,经倒置显微镜观察:3T3-16组细胞着色脂滴明显少于3T3-3.1组。过表达LRP16组其过氧化物酶体增殖物激活受体共激活因子-1α、解偶联蛋白2以及肌肉型肉毒碱棕榈酰转移酶1的mRNA水平表达上调。结论:LRP16可能具有使白色脂肪细胞的能量代谢向棕色脂肪细胞特性转变的作用。三:LRP16基因对脂肪因子表达的影响目的:探讨LRP16基因对脂肪因子的影响。方法:使用Real-time PCR技术检测两组脂肪细胞的脂联素和瘦素mRNA的相对表达量。结果:过表达LRP16组其脂联素和瘦素mRNA水平表达上调。结论:LRP16基因在整体层面上可能有促进能量代谢、改善糖耐量等的作用。结论 1.LRP16对脂肪细胞总体的效应可能是促进(微)炎症状态,对脂肪分化、胰岛素抵抗以及糖脂代谢都有影响。 2.LRP16可能具有使白色脂肪细胞的能量代谢向棕色脂肪细胞特性转变的作用,在细胞层面上促进能量代谢。 3.LRP16基因在整体层面上可能有促进能量代谢、改善糖耐量等的作用。以上研究结果表明:LRP16在脂肪细胞的代谢方面发挥着重要的作用。
[Abstract]:LRP16 is a human gene cloned from the peripheral blood lymphocytes of healthy adults. It is highly expressed in a variety of estrogen dependent tumors. In recent years, the metabolism of tumor tissues has become a hot spot. Some of the oncogenes do not necessarily play a role in promoting proliferation and inhibiting apoptosis. They can be adapted to adapt the metabolic patterns of tumor tissues to adapt them. Hypoxia, the absence of an environment for the supply of nutrients, can survive. This suggests that the oncogene may also affect the metabolic pattern of the body - and there is now evidence for this. In addition, some obesity regulatory genes have been shown to play a role in the occurrence of cancer. "Common origin", that is, the overactivation (or inhibition) of certain genes may lead to the simultaneous occurrence of tumor and obesity.LRP16 as a oncogene associated with the role of estrogen, and is likely to play a role in the metabolism of nutrients in the body. Therefore, this topic hopes to demonstrate the differentiation of LRP16 on the adipocytes at the cellular level. There is an impact on Isle resistance.
This study is divided into 3 parts:
1: To study the effect of LRP16 gene on the function of mature adipocyte using gene chip technology: To explore the effect of LRP16 gene on the function of mature adipocytes and its potential clinical significance. Methods: (1) the preadipocyte before induction of classical adipocyte induction is mature adipocytes. (2) high throughput gene chip analysis technique, through comparison The differentially expressed genes expressed in the mature adipocytes of LRP16 and the normal expression group, analyzed the possible signal pathways and target genes that LRP16 might involve, and established the direction for further study. Results: there were 1222 differentially expressed genes between the experimental group and the control group, of which 653 were up and 569 down-regulated. Among them, many were associated with fat differentiation and insulin. Resistance and glycolipid signaling pathways. Conclusion: for adipocytes, the overall function of LRP16 is to promote (micro) inflammatory state and affect fat differentiation, insulin resistance, and glycolipid metabolism.
Two: the LRPl6 gene may enhance the energy metabolism of the cells by promoting the expression of PGC-1 A: transfection of 3T3-L1 adipocytes to LRP16 (3T3-16) through plasmid transfection. The effect of LRP16 on lipid droplet formation was observed under microscope by oil red O. Real-time PCR technique was used to detect 3T3-16 and 3T3-3.1 (control group) two. Results: the relative expression of adipocytes and heat producing gene mRNA. Results: after the adipocytes were induced to mature, the fat cells were stained with oil red O and observed by inverted microscope: the coloured lipid droplets in the 3T3-16 group were significantly less than that of the 3T3-3.1 group. The peroxisome proliferator activated receptor co activator -1 alpha, uncoupling protein 2 and muscle were expressed in the LRP16 group. The mRNA expression of botuline palmityl transferase 1 is up-regulated. Conclusion: LRP16 may have the role of energy metabolism in white adipocytes to the transformation of brown adipocytes. Three: the effect of LRP16 gene on the expression of fat factor
Objective: To investigate the effect of LRP16 gene on adipose factors. Methods: Real-time PCR technique was used to detect the relative expression of adiponectin and leptin mRNA in two groups of adipocytes. Results: the expression of adiponectin and leptin mRNA in the LRP16 group was up-regulated. Conclusion: the LRP16 gene may promote energy metabolism and improve the glucose tolerance on the whole layer. The role.
conclusion
The overall effect of 1.LRP16 on adipocytes may be to promote (micro) inflammatory state, and to affect fat differentiation, insulin resistance and glucose and lipid metabolism.
2.LRP16 may play a role in transforming the energy metabolism of white adipocytes into brown adipocytes, and promote energy metabolism at the cellular level.
The 3.LRP16 gene may have the role of promoting energy metabolism and improving glucose tolerance at the overall level. The above results show that LRP16 plays an important role in the metabolism of adipocytes.
【学位授予单位】：中国人民解放军军医进修学院
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R329

【参考文献】