Embelin对脂肪生成及高脂饮食诱导小鼠肥胖的影响
发布时间：2018-09-19 17:54
【摘要】：背景与目的:近几十年来,伴随着人类生活方式的改变和社会经济发展,全球范围内的肥胖率呈现持续上升趋势。肥胖是一种慢性疾病,是指由于机体脂肪细胞体积肥大或数量增加导致的机体体重超过标准体重的20%及以上或者体重指数25kg/m2的病理状态。是糖尿病、心脑血管疾病、骨关节病、癌症等慢性病和社会心理障碍的重要危险因素,被世界卫生组织列为威胁人类健康的十大疾病之一。因此,肥胖需要积极预防和治疗。Embelin(恩贝素)是从紫金牛科(Myrsinaceae.Isoln)植物中提取的一种醌类化合物。已有文献研究表明其对于高脂饮食诱导的肥胖及其相关并发症有预防作用。本研究旨在于探讨Embelin是否通过抑制脂肪生成从而抑制肥胖。方法:1.分别用二甲基亚砜(DMSO)和不同浓度的Embelin处理骨髓基质细胞系ST2和间充质干细胞系C3H10T1/2,而后对处理过的细胞进行成脂诱导,通过油红O染色、q RT-PCR和Western blotting等方法从细胞分化程度、脂肪生成相关基因m RNA表达水平及相关蛋白质表达水平来评估embelin对ST2和C3H10T1/2细胞脂肪生成的影响;2采用4周龄的雄性C57BL/6小鼠,通过饲喂高脂饲料构建小鼠肥胖模型,喂养同时皮下注射不同剂量的Embelin,造模过程中记录各组小鼠体重,造模成功后处死实验组与对照组小鼠,分离腹股沟脂肪组织称取并记录其重量,以此确定Embelin对肥胖的影响;3、分离实验组与对照组小鼠附睾脂肪组织,提取RNA,逆转录,通过q RT-PCR检测脂肪组织中脂肪生成关键转录因子和标记基因的表达水平;4、各组小鼠尾静脉取血进行口服糖耐量试验,以此来评估embelin能否改善肥胖相关的糖耐量减低;5、检测小鼠血清胰岛素和葡萄糖浓度,进行HOMA-IR分析,以确定embelin能否改善肥胖相关的胰岛素抵抗。结果:1、油红O染色表明Embelin对骨髓基质细胞系ST2和间充质干细胞系C3H10T1/2细胞脂肪生成有抑制作用,q RT-PCR和Western blotting结果表明Embelin能抑制脂肪生成标记基因固醇调节元件结合蛋白1(sterol regulatory element-binding protein-1,Srebp-1)、已酰辅酶A羧化酶1(acetyl-Co A carboxylase 1,Acc1),脂肪酸合成酶1(fatty acid synthase,Fasn)和硬脂酰辅酶A脱氢酶1(stearoyl-Co A desaturase,Scd1)的表达,且有一定剂量依赖性;2、模型组(即高脂饲料喂养组)小鼠较对照组(即普通饲料喂养组)小鼠体重明显增加,造模成功,而饲喂高脂饲料伴随embelin皮下注射组小鼠的体重较对照组明显降低,同时对照组小鼠腹股沟脂肪垫重量明显重于高脂饲料喂养伴随皮下注射embelin组,且有一定的剂量依赖关系,表明embelin能抑制小鼠肥胖;3、注射Embelin组脂肪生成关键转录因子和标记基因srebp-1、Acc1、Fasn、Scd1表达水平均较对照组低,说明Embelin能够在体内抑制脂肪生成;4、各组小鼠尾静脉取血口服糖耐量试验显示模型组空腹血糖较对照组显著升高,血糖峰值亦明显升高,T120min时间点血糖值仍明显高于对照组,说明肥胖小鼠存在糖耐量损伤。而Embelin处理组血糖浓度变化与对照组相比无显著差异。表明Embelin可改善肥胖小鼠的糖耐量损伤;5、各组小鼠HOMA-IR(稳态胰岛素评估指数)分析显示,模型组HOMA-IR大于embelin组,说明embelin能改善肥胖小鼠的胰岛素抵抗。结论:1、Embelin对ST2细胞和C3H10T1/2细胞脂肪生成有抑制作用;2、Embelin能抑制脂肪生成从而抑制肥胖;同时Embelin能改善肥胖相关的糖耐量减低和胰岛素抵抗。
[Abstract]:BACKGROUND & OBJECTIVE: In recent decades, with the change of human life style and the development of social economy, the obesity rate has been on the rise all over the world. Obesity is a chronic disease, which means that the body weight exceeds 20% or more of the standard body weight or body mass index (BMI) due to the hypertrophy or increase of adipocytes. The pathological state of 25 kg/m2 is an important risk factor for diabetes, cardiovascular and cerebrovascular diseases, osteoarthropathy, cancer and other chronic diseases and psychosocial disorders. It is listed by the World Health Organization as one of the ten diseases threatening human health. Therefore, obesity needs active prevention and treatment. Embelin (Embelin) is a plant from Myrsinaceae. Isoln. A kind of quinone compound was extracted from human bone marrow stromal cells (BMSCs). It has been reported that it can prevent obesity induced by high fat diet and its related complications. The purpose of this study was to investigate whether Embelin can inhibit obesity by inhibiting fat production. Methods: 1. BMSCs were treated with dimethyl sulfoxide (DMSO) and different concentrations of Embelin, respectively. Stem cell line ST 2 and mesenchymal stem cell line C3H10T1/2 were induced to adipogenesis. The effects of Embelin on adipogenesis of ST 2 and C3H10T1/2 cells were evaluated by oil red O staining, Q RT-PCR and Western blotting. Four-week-old male C57BL/6 mice were fed with high-fat diet to establish obesity model in mice. Different doses of Embelin were injected subcutaneously at the same time. The weight of mice in each group was recorded during the modeling process. After successful modeling, the mice in the experimental group and the control group were sacrificed. 3. Isolate the epididymal adipose tissue of experimental group and control group, extract RNA, reverse transcription, detect the expression of key transcription factors and marker genes in adipose tissue by Q RT-PCR; 4. Blood samples from tail vein of each group were taken for oral glucose tolerance test to evaluate whether Embelin can improve obesity-related glucose tolerance. Results: 1. Oil red O staining showed that Embelin could inhibit adipogenesis of bone marrow stromal cell line ST 2 and mesenchymal stem cell line C3H10T1/2 cells, Q RT-PCR and Western blotting results table. Embelin inhibited the expression of sterol regulatory element-binding protein-1 (Srebp-1), acetyl-Co A carboxylase-1 (Acc-1), fatty acid synthase-1 (Fasn) and stearoyl-Co A dehydrogenase-1 (Scd-1) in adipogenic markers. 2. The weight of mice in the model group (i.e. the high-fat diet group) was significantly higher than that in the control group (i.e. the common diet group), and the weight of mice fed with high-fat diet and subcutaneous injection of Embelin was significantly lower than that in the control group. Meanwhile, the weight of groin fat pad in the control group was significantly heavier than that in the high-fat diet group. The expression levels of key transcription factors and marker genes srebp-1, Acc1, Fasn and Scd1 were lower in the Embelin group than in the control group, indicating that Embelin could inhibit fat production in vivo. The blood glucose tolerance test showed that the fasting blood glucose and the peak blood glucose in the model group were significantly higher than those in the control group, and the blood glucose level at T120 min was still significantly higher than that in the control group, indicating that there was impaired glucose tolerance in obese mice. 5. The HOMA-IR analysis showed that HOMA-IR in model group was higher than that in Embelin group, indicating that Embelin could improve insulin resistance in obese mice. Belin can improve obesity related impaired glucose tolerance and insulin resistance.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.2
本文编号：2250888
[Abstract]:BACKGROUND & OBJECTIVE: In recent decades, with the change of human life style and the development of social economy, the obesity rate has been on the rise all over the world. Obesity is a chronic disease, which means that the body weight exceeds 20% or more of the standard body weight or body mass index (BMI) due to the hypertrophy or increase of adipocytes. The pathological state of 25 kg/m2 is an important risk factor for diabetes, cardiovascular and cerebrovascular diseases, osteoarthropathy, cancer and other chronic diseases and psychosocial disorders. It is listed by the World Health Organization as one of the ten diseases threatening human health. Therefore, obesity needs active prevention and treatment. Embelin (Embelin) is a plant from Myrsinaceae. Isoln. A kind of quinone compound was extracted from human bone marrow stromal cells (BMSCs). It has been reported that it can prevent obesity induced by high fat diet and its related complications. The purpose of this study was to investigate whether Embelin can inhibit obesity by inhibiting fat production. Methods: 1. BMSCs were treated with dimethyl sulfoxide (DMSO) and different concentrations of Embelin, respectively. Stem cell line ST 2 and mesenchymal stem cell line C3H10T1/2 were induced to adipogenesis. The effects of Embelin on adipogenesis of ST 2 and C3H10T1/2 cells were evaluated by oil red O staining, Q RT-PCR and Western blotting. Four-week-old male C57BL/6 mice were fed with high-fat diet to establish obesity model in mice. Different doses of Embelin were injected subcutaneously at the same time. The weight of mice in each group was recorded during the modeling process. After successful modeling, the mice in the experimental group and the control group were sacrificed. 3. Isolate the epididymal adipose tissue of experimental group and control group, extract RNA, reverse transcription, detect the expression of key transcription factors and marker genes in adipose tissue by Q RT-PCR; 4. Blood samples from tail vein of each group were taken for oral glucose tolerance test to evaluate whether Embelin can improve obesity-related glucose tolerance. Results: 1. Oil red O staining showed that Embelin could inhibit adipogenesis of bone marrow stromal cell line ST 2 and mesenchymal stem cell line C3H10T1/2 cells, Q RT-PCR and Western blotting results table. Embelin inhibited the expression of sterol regulatory element-binding protein-1 (Srebp-1), acetyl-Co A carboxylase-1 (Acc-1), fatty acid synthase-1 (Fasn) and stearoyl-Co A dehydrogenase-1 (Scd-1) in adipogenic markers. 2. The weight of mice in the model group (i.e. the high-fat diet group) was significantly higher than that in the control group (i.e. the common diet group), and the weight of mice fed with high-fat diet and subcutaneous injection of Embelin was significantly lower than that in the control group. Meanwhile, the weight of groin fat pad in the control group was significantly heavier than that in the high-fat diet group. The expression levels of key transcription factors and marker genes srebp-1, Acc1, Fasn and Scd1 were lower in the Embelin group than in the control group, indicating that Embelin could inhibit fat production in vivo. The blood glucose tolerance test showed that the fasting blood glucose and the peak blood glucose in the model group were significantly higher than those in the control group, and the blood glucose level at T120 min was still significantly higher than that in the control group, indicating that there was impaired glucose tolerance in obese mice. 5. The HOMA-IR analysis showed that HOMA-IR in model group was higher than that in Embelin group, indicating that Embelin could improve insulin resistance in obese mice. Belin can improve obesity related impaired glucose tolerance and insulin resistance.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.2
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相关期刊论文 前2条
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2 鞠大鹏;詹丽杏;;脂肪细胞分化及其调控的研究进展[J];中国细胞生物学学报;2010年05期
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