棕色脂肪干細胞的獲取及其在代謝調(diào)控中的作用和ENGRAILED1基因?qū)ψ厣炯毎傻挠绊?/H1>
發(fā)布時間：2018-03-09 12:02
本文選題：棕色脂肪干細胞 切入點：代謝調(diào)控 出處：《南京農(nóng)業(yè)大學》2016年博士論文 論文類型：學位論文
【摘要】：肥胖是由于能量攝入大于能量消耗導(dǎo)致的一種慢性代謝病,會引起胰島素抵抗,增加糖尿病、多囊卵巢綜合癥(PCOS)等眾多肥胖相關(guān)的代謝疾病的風險。有研究指出,肥胖也是一型糖尿病的誘因。一型糖尿病是一種由胰島素分泌不足導(dǎo)致的血糖代謝失調(diào)疾病,通過代謝調(diào)控來改善其癥狀是一條重要的途徑。棕色脂肪(BAT)廣泛存在于小型哺乳動物和人類的新生兒時期,具有高效的產(chǎn)熱耗能特性,可以有效改善肥胖和糖脂代謝紊亂。成人體內(nèi)也普遍存在功能性棕色脂肪,但它們的含量較低,并與身體質(zhì)量指數(shù)(BMI)程負相關(guān)。有研究指出移植BAT可以抑制肥胖、治療糖尿病、改善胰島素抵抗和改善PCOS。這說明,BAT在肥胖相關(guān)代謝疾病及能量代謝紊亂導(dǎo)致的繁殖障礙方面具有潛在的治療應(yīng)用價值。然而,大量移植棕色脂肪并不現(xiàn)實。一方面是異體來源的棕色脂肪細胞可能會產(chǎn)生免疫排斥,另一方面是棕色脂肪細胞的來源十分有限。另外,有關(guān)人類棕色脂肪細胞的應(yīng)用研究還很少。因此,如何得到足量且有活性的棕色脂肪細胞,探索棕色脂肪細胞的潛在應(yīng)用成了我們關(guān)注的重點。鑒于此,本研究對如何獲取足量且有活性的棕色脂肪細胞及棕色脂肪細胞的代謝調(diào)控作用進行了初步探索。本研究成功獲取并分離鑒定了人類胚胎經(jīng)典部位和腎周部位的棕色脂肪干細胞,并分析了它們的體外棕色化潛能和轉(zhuǎn)錄水平的差異,結(jié)果發(fā)現(xiàn)人胚胎腎周脂肪干細胞也具有良好的棕色化潛能;同時也初步探索了棕色脂肪干細胞對糖尿病的治療作用及其體外分化后的分泌蛋白質(zhì)譜特點,結(jié)果發(fā)現(xiàn)移植棕色脂肪干細胞可以有效改善葡萄糖耐受水平;研究了 Engrailed1基因?qū)ψ厣炯毎傻挠绊?結(jié)果發(fā)現(xiàn)Engrailed1可以促進棕色脂肪細胞的生成,從基因修飾角度為如何獲取更多具有活性的棕色脂肪細胞提供了思路進而為探索棕色脂肪干細胞的應(yīng)用提供了基礎(chǔ)。通過我們的研究可以揭示棕色脂肪細胞更多分子水平的特性和潛在的應(yīng)用價值,并從基因修飾角度為如何獲取更多具有活性的棕色脂肪細胞提供了新的思路和應(yīng)用支持,為改善動物和人的糖尿病、肥胖相關(guān)代謝疾病及能量代謝失調(diào)導(dǎo)致的繁殖障礙提供一定的理論依據(jù)和新的技術(shù)支撐。
[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.
【學位授予單位】：南京農(nóng)業(yè)大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R589.2
【參考文獻】
相關(guān)期刊論文 前6條
1 張瀚林;黃園園;李赫鐘;金萬洙;;Zic1對C_3H_(10)T_(1/2)細胞棕色脂肪分化的負調(diào)控研究(英文)[J];Science Bulletin;2015年11期
2 董忠;李剛;謝瑾;周瀅;張京;趙越;焦淑芳;;北京市成年人主要慢性病流行特征分析[J];中國公共衛(wèi)生;2010年03期
3 羅獻梅;陳代文;;棕色脂肪組織的生理功能及影響因素[J];飼料工業(yè);2007年19期
4 趙文華;翟屹;胡建平;王建生;楊正雄;孔靈芝;陳春明;;中國超重和肥胖造成相關(guān)慢性疾病的經(jīng)濟負擔研究[J];中華流行病學雜志;2006年07期
5 武陽豐,馬冠生,胡永華,李艷平,李賢,崔朝輝,陳春明,孔靈芝;中國居民的超重和肥胖流行現(xiàn)狀[J];中華預(yù)防醫(yī)學雜志;2005年05期
6 張冬梅,周智廣,胡白瑛,魏佳莉,黃干,王建平;自發(fā)酮癥起病的肥胖糖尿病患者的臨床特征及分型[J];中華內(nèi)分泌代謝雜志;2003年03期
，
本文編號：1588448
本文鏈接：http://sikaile.net/kejilunwen/jiyingongcheng/1588448.html
本文選題：棕色脂肪干細胞 切入點：代謝調(diào)控 出處：《南京農(nóng)業(yè)大學》2016年博士論文 論文類型：學位論文
【摘要】：肥胖是由于能量攝入大于能量消耗導(dǎo)致的一種慢性代謝病,會引起胰島素抵抗,增加糖尿病、多囊卵巢綜合癥(PCOS)等眾多肥胖相關(guān)的代謝疾病的風險。有研究指出,肥胖也是一型糖尿病的誘因。一型糖尿病是一種由胰島素分泌不足導(dǎo)致的血糖代謝失調(diào)疾病,通過代謝調(diào)控來改善其癥狀是一條重要的途徑。棕色脂肪(BAT)廣泛存在于小型哺乳動物和人類的新生兒時期,具有高效的產(chǎn)熱耗能特性,可以有效改善肥胖和糖脂代謝紊亂。成人體內(nèi)也普遍存在功能性棕色脂肪,但它們的含量較低,并與身體質(zhì)量指數(shù)(BMI)程負相關(guān)。有研究指出移植BAT可以抑制肥胖、治療糖尿病、改善胰島素抵抗和改善PCOS。這說明,BAT在肥胖相關(guān)代謝疾病及能量代謝紊亂導(dǎo)致的繁殖障礙方面具有潛在的治療應(yīng)用價值。然而,大量移植棕色脂肪并不現(xiàn)實。一方面是異體來源的棕色脂肪細胞可能會產(chǎn)生免疫排斥,另一方面是棕色脂肪細胞的來源十分有限。另外,有關(guān)人類棕色脂肪細胞的應(yīng)用研究還很少。因此,如何得到足量且有活性的棕色脂肪細胞,探索棕色脂肪細胞的潛在應(yīng)用成了我們關(guān)注的重點。鑒于此,本研究對如何獲取足量且有活性的棕色脂肪細胞及棕色脂肪細胞的代謝調(diào)控作用進行了初步探索。本研究成功獲取并分離鑒定了人類胚胎經(jīng)典部位和腎周部位的棕色脂肪干細胞,并分析了它們的體外棕色化潛能和轉(zhuǎn)錄水平的差異,結(jié)果發(fā)現(xiàn)人胚胎腎周脂肪干細胞也具有良好的棕色化潛能;同時也初步探索了棕色脂肪干細胞對糖尿病的治療作用及其體外分化后的分泌蛋白質(zhì)譜特點,結(jié)果發(fā)現(xiàn)移植棕色脂肪干細胞可以有效改善葡萄糖耐受水平;研究了 Engrailed1基因?qū)ψ厣炯毎傻挠绊?結(jié)果發(fā)現(xiàn)Engrailed1可以促進棕色脂肪細胞的生成,從基因修飾角度為如何獲取更多具有活性的棕色脂肪細胞提供了思路進而為探索棕色脂肪干細胞的應(yīng)用提供了基礎(chǔ)。通過我們的研究可以揭示棕色脂肪細胞更多分子水平的特性和潛在的應(yīng)用價值,并從基因修飾角度為如何獲取更多具有活性的棕色脂肪細胞提供了新的思路和應(yīng)用支持,為改善動物和人的糖尿病、肥胖相關(guān)代謝疾病及能量代謝失調(diào)導(dǎo)致的繁殖障礙提供一定的理論依據(jù)和新的技術(shù)支撐。
[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.
【學位授予單位】：南京農(nóng)業(yè)大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R589.2
【參考文獻】
相關(guān)期刊論文 前6條
1 張瀚林;黃園園;李赫鐘;金萬洙;;Zic1對C_3H_(10)T_(1/2)細胞棕色脂肪分化的負調(diào)控研究(英文)[J];Science Bulletin;2015年11期
2 董忠;李剛;謝瑾;周瀅;張京;趙越;焦淑芳;;北京市成年人主要慢性病流行特征分析[J];中國公共衛(wèi)生;2010年03期
3 羅獻梅;陳代文;;棕色脂肪組織的生理功能及影響因素[J];飼料工業(yè);2007年19期
4 趙文華;翟屹;胡建平;王建生;楊正雄;孔靈芝;陳春明;;中國超重和肥胖造成相關(guān)慢性疾病的經(jīng)濟負擔研究[J];中華流行病學雜志;2006年07期
5 武陽豐,馬冠生,胡永華,李艷平,李賢,崔朝輝,陳春明,孔靈芝;中國居民的超重和肥胖流行現(xiàn)狀[J];中華預(yù)防醫(yī)學雜志;2005年05期
6 張冬梅,周智廣,胡白瑛,魏佳莉,黃干,王建平;自發(fā)酮癥起病的肥胖糖尿病患者的臨床特征及分型[J];中華內(nèi)分泌代謝雜志;2003年03期
，本文編號：1588448
本文鏈接：http://sikaile.net/kejilunwen/jiyingongcheng/1588448.html
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