棕色脂肪干细胞的获取及其在代谢调控中的作用和ENGRAILED1基因对棕色脂肪细胞生成的影响

发布时间：2018-03-09 12:02

本文选题：棕色脂肪干细胞　切入点：代谢调控　出处：《南京农业大学》2016年博士论文　论文类型：学位论文

【摘要】：肥胖是由于能量摄入大于能量消耗导致的一种慢性代谢病,会引起胰岛素抵抗,增加糖尿病、多囊卵巢综合症(PCOS)等众多肥胖相关的代谢疾病的风险。有研究指出,肥胖也是一型糖尿病的诱因。一型糖尿病是一种由胰岛素分泌不足导致的血糖代谢失调疾病,通过代谢调控来改善其症状是一条重要的途径。棕色脂肪(BAT)广泛存在于小型哺乳动物和人类的新生儿时期,具有高效的产热耗能特性,可以有效改善肥胖和糖脂代谢紊乱。成人体内也普遍存在功能性棕色脂肪,但它们的含量较低,并与身体质量指数(BMI)程负相关。有研究指出移植BAT可以抑制肥胖、治疗糖尿病、改善胰岛素抵抗和改善PCOS。这说明,BAT在肥胖相关代谢疾病及能量代谢紊乱导致的繁殖障碍方面具有潜在的治疗应用价值。然而,大量移植棕色脂肪并不现实。一方面是异体来源的棕色脂肪细胞可能会产生免疫排斥,另一方面是棕色脂肪细胞的来源十分有限。另外,有关人类棕色脂肪细胞的应用研究还很少。因此,如何得到足量且有活性的棕色脂肪细胞,探索棕色脂肪细胞的潜在应用成了我们关注的重点。鉴于此,本研究对如何获取足量且有活性的棕色脂肪细胞及棕色脂肪细胞的代谢调控作用进行了初步探索。本研究成功获取并分离鉴定了人类胚胎经典部位和肾周部位的棕色脂肪干细胞,并分析了它们的体外棕色化潜能和转录水平的差异,结果发现人胚胎肾周脂肪干细胞也具有良好的棕色化潜能;同时也初步探索了棕色脂肪干细胞对糖尿病的治疗作用及其体外分化后的分泌蛋白质谱特点,结果发现移植棕色脂肪干细胞可以有效改善葡萄糖耐受水平;研究了 Engrailed1基因对棕色脂肪细胞生成的影响,结果发现Engrailed1可以促进棕色脂肪细胞的生成,从基因修饰角度为如何获取更多具有活性的棕色脂肪细胞提供了思路进而为探索棕色脂肪干细胞的应用提供了基础。通过我们的研究可以揭示棕色脂肪细胞更多分子水平的特性和潜在的应用价值,并从基因修饰角度为如何获取更多具有活性的棕色脂肪细胞提供了新的思路和应用支持,为改善动物和人的糖尿病、肥胖相关代谢疾病及能量代谢失调导致的繁殖障碍提供一定的理论依据和新的技术支撑。
[Abstract]:Obesity is a chronic metabolic disease due to energy intake is greater than the energy consumption causes, can cause insulin resistance, diabetes, polycystic ovary syndrome (PCOS) risk of obesity related metabolic diseases. Studies have shown that obesity is a cause of diabetes. Diabetes mellitus is a lack of insulin secretion by glucose metabolism caused by metabolic regulation disorders, to improve the symptoms is an important way. Brown fat (BAT) widely exists in small mammals and humans during neonatal period, has characteristics of high heat consumption, can effectively improve the obesity and lipid metabolism disorders. Adults are also common functional brown fat, but their content is low, and the body mass index (BMI) process of negative correlation. Studies have shown that transplantation of BAT can inhibit obesity, diabetes, improve insulin resistance and improve This shows that PCOS., a therapeutic potential reproductive disorder BAT in obesity related metabolic disorders and metabolic disorder caused. However, a large number of brown fat transplantation is not realistic. On the one hand is the source of allogeneic brown fat cells may lead to immune rejection, on the other hand is a very limited source of brown fat cells. In addition, application study on human brown fat cells are rare. Therefore, how to obtain enough and the activity of brown fat cells, to explore the potential application of brown fat cells has become the focus of our attention. In view of this, the research on how to obtain enough and have explored the metabolism activity of brown fat and brown fat cells cells. This study successfully obtained the isolation and identification of human embryonic kidney and peripheral portion of the classic parts of brown adipose stem cells, and analyzes their The difference in browning potential and transcription level, results showed that human embryonic kidney fat stem cells also have brown potential good; also explored the therapeutic effect on diabetes and cell differentiation in vitro after protein secretion characteristics of brown fat, found that can effectively improve the glucose tolerance level of brown adipose stem cells transplantation study on the effect of Engrailed1 gene; generation of brown fat cells, the results showed that Engrailed1 can promote the formation of brown fat cells, from the angle of genetically modified to obtain more active brown fat cells provides a way to explore and provide a basis for the application of brown adipose stem cells. Through our research can reveal the characteristics of Brown more the molecular level of fat cells and potential application value, and from the perspective of gene modification for how to obtain more Active brown adipocytes provide new ideas and application support, and provide certain theoretical basis and new technical support for improving animal and human diabetes, obesity related metabolic diseases and energy metabolism disorders.

【学位授予单位】：南京农业大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R589.2

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