Irisin对脂肪细胞的脂解和自分泌作用及其与PCOS患者骨密度和身体成分的关联性研究

发布时间：2018-03-05 09:31

本文选题：irisin　切入点：脂解　出处：《吉林大学》2016年博士论文　论文类型：学位论文

【摘要】：2012年初,有人发现irisin作为一种与运动相关的肌因子和脂肪因子,可以使白色脂肪细胞“棕色化”,并且与肥胖及其相关代谢疾病有密切的联系。因此,这种内分泌因子引起科学界和医学界的广泛关注。已经知道,irisin可以增加脂肪细胞中UCP1蛋白的表达,并且可以在体外促进成骨细胞的分化,但是,关于irisin对脂肪细胞的脂解影响的研究还不透彻,而且,irisin对脂肪细胞的自分泌的影响尚未被研究。另外,多囊卵巢综合症是一种与肥胖有关的代谢异常的内分泌疾病,其发病机理目前还不甚清楚,irisin是否与PCOS患者的身体成分有关也有待进一步的研究。基于这些研究背景,本文展开如下研究:首先,建立一个有效的大肠杆菌的表达和纯化GST-irisin的体系,通过对CCK-8和解偶联蛋白1的mRNA的检测从而验证融合蛋白的生物活性。实验数据表明,GST-irisin可以调控脂解相关基因甘油三酯脂肪酶和激素敏感性脂肪酶的m RNA表达和脂肪酸结合蛋白4的蛋白量,从而在3T3-L1脂肪细胞中增加甘油的释放并减少脂滴的积累。此外,外源GST-irisin可以通过调节FNDC5的表达量,进而促进它的自分泌。GST-irisin还可以调控3T3-L1脂肪细胞的葡萄糖摄取。综上,重组GST-irisin可以促进脂类分解和自分泌,本文推测它可以用于防治肥胖及其相关代谢疾病。其次,招募52名多囊卵巢综合症患者和39名对照者,并对其血清中的性激素、空腹胰岛素和C肽进行测定。采用ELISA实验测定空腹血清irisin和脂联素浓度,利用双能X线骨密度仪对其身体成分和骨密度进行测定。检测数据表明,与对照组相比,多囊卵巢综合征患者具有不同的身体成分。虽然PCOS组血清irisin水平有所降低,但是没有统计学差异,PCOS患者的脂联素水平明显降低,体内irisin水平与BMI没有相关性。统计分析表明,对照组中的irisin与骨密度正相关,而在PCOS组中校正年龄和BMI后,irisin与骨密度呈负相关。此外,PCOS组中瘦体重显著影响irisin的水平。在两组中没有发现脂联素与身体成分和骨密度之间的相关性。因此,本文认为,PCOS患者中异常分布的身体成分可能影响体内的irisin水平,同时,不同器官之间通过irisin互相“串话”,并且irisin与PCOS的病程发展有关。
[Abstract]:In early 2012, it was found that irisin, as a muscle factor and fat factor associated with exercise, can "brown" white fat cells and be closely associated with obesity and related metabolic diseases. The endocrine factor has attracted widespread attention in the scientific and medical fields. It has been known that UCP1 protein expression in adipocytes can be increased and that it can promote osteoblast differentiation in vitro, but, The effect of irisin on adipocytes is not well studied, and the effect of irisin on adipocyte autocrine has not been studied. In addition, polycystic ovary syndrome (PCOS) is a metabolic disorder associated with obesity. It is not clear that the pathogenesis of PCOS is related to the body composition of patients with PCOS. Based on these research background, the following studies are carried out in this paper: first of all, To establish an effective system for the expression and purification of GST-irisin in Escherichia coli. The bioactivity of the fusion protein was verified by the detection of mRNA of CCK-8 and uncoupling protein 1. The experimental data showed that GST-irisin could regulate the expression of mRNA and lipase of triglyceride lipase and hormone sensitive lipase. Fatty acid binding protein 4 protein, In addition, exogenous GST-irisin could regulate the glucose uptake of 3T3-L1 adipocytes by regulating the expression of FNDC5, thereby promoting its autocrine, GST-irisin, which could increase the release of glycerol and decrease the accumulation of lipid droplets in 3T3-L1 adipocytes. In addition, exogenous GST-irisin could also regulate the glucose uptake of 3T3-L1 adipocytes by regulating the expression of FNDC5. Recombinant GST-irisin can promote lipid decomposition and autocrine. We speculate that it can be used to prevent and treat obesity and related metabolic diseases. Secondly, 52 patients with polycystic ovary syndrome and 39 controls were recruited and their serum sex hormones were determined. Fasting insulin and C-peptide were measured. Fasting serum irisin and adiponectin concentrations were measured by ELISA test, and body composition and bone mineral density were measured by dual energy X-ray absorptiometry. Although the serum irisin level in PCOS group was decreased, there was no significant difference in adiponectin level, and there was no correlation between irisin level and BMI. Irisin in the control group was positively correlated with bone mineral density. In the PCOS group, there was a negative correlation between the corrected age and the bone mineral density (BMD) after BMI. In addition, the lean weight in the BMI group significantly affected the level of irisin. There was no correlation between adiponectin and body composition and bone mineral density in the two groups. Therefore, there was no correlation between adiponectin and body composition and bone mineral density. It is suggested that the abnormal distribution of body components in PCOS patients may affect the level of irisin in the body, at the same time, the different organs talk to each other through irisin, and irisin is related to the course of PCOS.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R711.75

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