钙信号通过IP3通路对正常与肥胖小鼠脂解作用的影响

发布时间：2018-02-26 16:25

本文关键词： IP3 膳食钙胞内钙脂肪沉积　出处：《西北农林科技大学》2011年硕士论文　论文类型：学位论文

【摘要】：钙在动物脂肪代谢中发挥着重要作用,膳食钙被证实有抗肥胖的作用,在对其作用机制的研究中,人们认为外源钙以膳食形式摄入体内,会改变体内细胞的钙浓度,使钙信号发生变化,从而引发一系列生物学效应。通过IP3通路钙库可以使胞内钙离子浓度升高,引起钙信号改变,但是目前对胞内钙浓度变化的研究主要集中在肌肉收缩和心血管疾病上,有关脂肪代谢的研究几乎没有。本研究以小鼠为实验动物,分别在肥胖和正常状态下用药物处理,小鼠随机分为对照组、去甲肾上腺素(NE)组、肝素组、钙组、钙+NE组和钙+肝素组。分析指标包括:体重、采食量、组织重、血脂水平、组织钙含量和组织中脂代谢相关基因mRNA和蛋白表达。旨在观察钙库和膳食钙引发的胞内钙浓度变化对脂肪代谢的影响。结果如下: 1.试验发现,肝素和膳食钙处理肥胖小鼠有显著的减肥效果(P0.01),减少体脂含量(P0.01),血清中TG和TC含量显著降低(P0.01),HDL-C水平却升高(P0.01),并且PPARγ、FAS和IP3R1的mRNA水平均降低(P0.01),HSLmRNA水平显著升高(P0.01),C/EBPα的mRNA水平无明显变化;去甲肾上腺素处理肥胖小鼠,效果与肝素相反,明显削弱减肥作用(P0.01);相比对照组,肝素组、钙组、钙+NE组和钙+肝素组的PPARγ、C/EBPα和FAS的蛋白表达量有所减少,ATGL的表达量有所增加;NE组的PPARγ、C/EBPα和FAS的蛋白表达量增大,而在ATGL上的蛋白表达量下降。膳食钙有显著减肥效果(P0.01),但钙+NE组的减肥效果弱于钙组(P0.01),钙+肝素组的减肥效果强于膳食钙的处理效果(P0.01)。说明IP3通路激活可引起胞内钙离子升高,脂肪蓄积增加;反之,脂肪蓄积减少。通过IP3通路,膳食钙可抑制胞内钙离子增加。 2.结果表明,NE、肝素和膳食钙处理正常小鼠,都表现出了对小鼠的体质量的抑制作用(P0.01),减少了附睾脂肪和肾周脂肪的重量(P0.01),增加了棕色脂肪组织重量(P0.01),血清中TG和TC含量显著降低(P0.01),HDL-C水平却升高(P0.01);NE可以增加IP3R1mRNA的表达量(P0.01),肝素和钙抑制了IP3R1mRNA的表达(P0.01)。NE、肝素和膳食钙的FAS、PPARγ和C/EBPα的mRNA均表现极显著下降(P0.01),HSL的mRNA表达显著上升(P0.01);NE组、肝素组、钙组、钙+NE组和钙+肝素组的PPARγ、C/EBPα和FAS的蛋白含量降低;NE组、肝素组、钙组、钙+NE组和钙+肝素组的ATGL蛋白含量升高。说明膳食钙通过IP3通路可抑制胞内钙离子增加,对动物体的脂肪代谢有抑制作用;动物体棕色脂肪组织可以极大的限制肥胖的发生。
[Abstract]:Calcium plays an important role in animal fat metabolism. Dietary calcium has been proved to have anti-obesity effect. In the study of its mechanism, it is believed that exogenous calcium intake in vivo will change the calcium concentration of cells in vivo. Through the IP3 pathway, calcium can increase the intracellular calcium concentration and cause the change of calcium signal. However, the current studies on intracellular calcium concentration mainly focus on muscle contraction and cardiovascular disease, and there are few studies on fat metabolism. In this study, mice were treated with drugs in obese and normal conditions. The mice were randomly divided into three groups: control group, NE group, heparin group, calcium group, calcium NE group and calcitonin group. The effects of calcium intake, tissue weight, blood lipid level, tissue calcium content and lipid metabolism-related genes mRNA and protein expression on lipid metabolism were observed in order to observe the effects of calcium pool and calcium induced changes in intracellular calcium concentration on lipid metabolism. 1. The experiment found that. Heparin and dietary calcium treatment could significantly reduce the weight loss of obese mice (P 0.01), decrease body fat content (P 0.01), decrease serum TG and TC (P 0.01), but increase HDL-C (P 0.01). However, the mRNA levels of PPAR 纬 FAS and IP3R1 decreased significantly (P 0.01) and HSL mRNA level increased significantly (P 0.01%), while the mRNA level of P0.01C / EBP 伪 did not change significantly. Compared with control group, heparin group, calcium group, heparin group, noradrenaline treated obese mice, the effect was contrary to heparin, significantly weakened the weight loss effect of P0.01, compared with control group, heparin group, calcium group, The protein expression of PPAR 纬 -C / EBP 伪 and FAS in calcium NE group and calcium heparin group was decreased. The expression of PPAR 纬 -C% EBP 伪 and FAS in NE group was increased, and the protein expression of PPAR 纬 -C% EBP 伪 and FAS increased in NE group. However, the protein expression on ATGL decreased. Dietary calcium had a significant effect on weight loss, but the effect of calcium NE group was weaker than that of calcium group P0.01, and that of calcium heparin group was stronger than that of dietary calcium treatment. The results showed that activation of IP3 pathway could cause the activation of IP3 pathway. Intracellular calcium increased, Fat accumulation increased, whereas fat accumulation decreased. Dietary calcium inhibited the increase of intracellular calcium ion through IP3 pathway. 2. The results showed that normal mice were treated with heparin and dietary calcium. All of them showed inhibitory effect on the body weight of mice, decreased the weight of epididymal fat and perirenal fat, increased the weight of brown adipose tissue and increased the weight of brown adipose tissue. The levels of TG and TC in serum decreased significantly the level of HDL-C of P0.01C, but increased the level of P0.01C, which increased IP3R1mRNA. The expression of IP3R1mRNA was inhibited by heparin and calcium. The mRNA of FASPPAR 纬 and C / EBP 伪 in heparin and dietary calcium decreased significantly. The protein contents of PPAR 纬 C / EBP 伪 and FAS in heparin group, calcium group, calcium NE group and calcium heparin group decreased in NE group, heparin group and calcium group, respectively. The content of ATGL protein in calcium NE group and calcium heparin group was increased, which indicated that dietary calcium could inhibit the increase of intracellular calcium ion through IP3 pathway and inhibit fat metabolism in animals, while brown adipose tissue in animal body could greatly limit the occurrence of obesity.
【学位授予单位】：西北农林科技大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363

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