發(fā)布時間：2018-06-01 11:04

  本文選題：高脂膳食 + 肥胖��； 參考：《江南大學》2015年碩士論文

【摘要】：目的:高脂膳食條件下不同個體對肥胖表現(xiàn)出不同的易感性,但具體機制未明。甲狀腺激素是機體能量代謝和脂質(zhì)代謝的重要調(diào)節(jié)因子,其代謝可能受到micro RNAs的調(diào)節(jié)。因此,本文主要從micro RNAs影響甲狀腺激素代謝角度探討了肥胖和肥胖抵抗機體表型差異出現(xiàn)的可能原因。通過飼喂高脂膳食建立肥胖和肥胖抵抗表型,探究高脂膳食誘導的甲狀腺激素代謝及相關micro RNAs的表達差異對小鼠肥胖和肥胖抵抗表型產(chǎn)生的可能影響。方法:120只C57BL/6雄性小鼠分別飼喂正常膳食(n=30,C組)和高脂膳食(n=90,HFD組)。7周時根據(jù)小鼠體重將HFD組分為肥胖組(體重最高的1/3,DIO)和肥胖抵抗組(體重最低的1/3,DIO-R)。分組后從C組、DIO組和DIO-R組中隨機選出10只分別在7周、17周和27周時處死以評價甲狀腺激素在高脂膳食飼喂早期、中期和晚期時對小鼠肥胖易感性的影響。用CLAMS動物代謝監(jiān)測系統(tǒng)測定小鼠的代謝狀況,分別測定血漿中甲狀腺激素水平和血脂水平。7周時對小鼠的肝臟進行micro RNAs測序,并采用熒光定量PCR驗證各個周期中甲狀腺激素代謝相關micro RNAs的m RNA水平,同時測定肝臟中Ⅰ型脫碘酶(D1)和甲狀腺激素受體β(TRβ)以及脂代謝相關基因的m RNA水平。Western blot測定小鼠肝臟中D1和TRβ的蛋白水平。分別對小鼠肝臟中micro RNAs的水平和D1、TRβ的表達及肝臟中micro RNAs的水平和血漿中甘油三酯(TG)、總膽固醇(TC)含量進行相關性分析。結果:高脂膳食短期飼喂(7周)時,DIO組的體重比C組的體重高了1.2倍以上,達到了肥胖的標準即造模成功,而C組和DIO-R組體重無顯著差異(P0.05)。根據(jù)測序結果篩選出三組小鼠肝臟中差異表達并能作用于甲狀腺激素代謝的micro RNAs:靶作用于D1翻譯過程的mi R-383,靶作用于TRβ轉(zhuǎn)錄過程的mi R-34a和mi R-146b。高脂膳食短期飼喂時,DIO組和DIO-R組肝臟中mi R-383,mi R-34a和mi R-146b的水平均低于C組。與DIO-R組相比,DIO組的血漿甲狀腺素(T4)和甲狀腺激素(T3)水平,肝臟中D1的蛋白水平和FAS的表達顯著高于DIO-R組,而TRβ的m RNA和蛋白水平及CPT1α、PGC1α和CYP7A1的表達顯著低于DIO-R組(P0.05)。DIO組的血漿TG水平顯著高于DIO-R組(P0.05),而兩組間TC水平無顯著差異(P0.05)。高脂膳食飼喂中期(17周)時,DIO組肝臟中mi R-383、mi R-34a和mi R-146b的表達均顯著高于DIO-R組,且D1,TRβ蛋白水平和血漿T3水平均顯著低于DIO-R組(P0.05)。DIO組肝臟中FAS的表達仍顯著高于DIO-R組;而DIO組肝臟中CPT1α、PGC1α和CYP7A1的的表達顯著低于DIO-R組(P0.05)。DIO組的體重、血漿TG水平和TC水平均顯著高于DIO-R組(P0.05)。高脂膳食飼喂后期(27周)時,DIO組肝臟中mi R-383顯著高于DIO-R組,肝臟中D1的蛋白水平和血漿T3水平顯著低于DIO-R組(P0.05)。三組小鼠肝臟中mi R-34a、mi R-146b和TRβ及CPT1α、PGC1α和CYP7A1的表達無顯著差異(P0.05)。DIO組的體重、FAS的表達量、TG、TC和LDL-C含量均顯著高于DIO-R組(P0.05)。相關性分析表明:肝臟中mi R-383和D1的蛋白水平呈顯著負相關(P0.05);肝臟中mi R-34a和TRβ的m RNA水平及蛋白水平均呈顯著負相關(P0.05);肝臟中mi R-146b和TRβ的m RNA水平及蛋白水平均呈顯著負相關(P0.05)。肝臟中mi R-34a和血漿中TG和TC含量均呈顯著正相關(P0.05);mi R-146b和血漿中TG和TC含量均正相關,但不顯著(P0.05);mi R-383和血漿中TG含量顯著正相關(P0.05),而mi R-383和血漿中TC含量正相關但不顯著(P0.05)。結論:高脂膳食飼喂在不同周期對DIO-R和DIO組小鼠肝臟中甲狀腺激素代謝相關micro RNAs表達的影響是不同的。與DIO-R組相比,高脂膳食飼喂早期DIO組小鼠肝臟中mi R-383的表達受到抑制,使得肝臟中D1的表達升高;而到高脂飼喂中期和后期時DIO組小鼠肝臟中mi R-34a和mi R-146b的表達升高,使得肝臟中TRβ的表達受到抑制。DIO-R和DIO組小鼠肝臟中mi R-383,mi R-34a和mi R-146b表達的不同變化使T3靶基因中脂代謝相關基因的表達出現(xiàn)差異,最終導致DIO組小鼠體重顯著高于DIO-R組,出現(xiàn)了肥胖和肥胖抵抗表型的差異。
[Abstract]:Objective: under the condition of high fat diet, different individuals have different susceptibility to obesity, but the specific mechanism is not clear. Thyroid hormone is an important regulator of the body's energy metabolism and lipid metabolism, and its metabolism may be regulated by micro RNAs. Therefore, this paper mainly discusses the obesity and fertilizer from the effect of micro RNAs on the metabolic angle of thyroid hormone. The possible causes of the phenotypic difference of fat resistance. Establish obesity and obesity resistance phenotype by feeding high fat diet, explore the possible effects of high fat diet induced thyroid hormone metabolism and the difference of micro RNAs expression on the obesity and obesity resistance phenotype of mice. Methods: 120 male C57BL/6 mice were fed to normal. Dietary (n=30, C) and high fat diet (group n=90, HFD) were divided into obese group (the highest weight 1/3, DIO) and the obesity resistance group (the lowest weight 1/3, DIO-R) according to the weight of the mice (the highest weight 1/3, DIO) and the obese group (the HFD group) at.7 weeks. The 10 rats were randomly selected from the C group, the DIO group and the 27 weeks to evaluate the thyroid hormone in the high fat diet. The effects of early, middle and late stage on the susceptibility to obesity in mice. The metabolic status of mice was measured by CLAMS animal metabolism monitoring system. The serum thyroid hormone level and blood lipid level were measured by micro RNAs sequencing at.7 weeks respectively. The fluorescence quantitative PCR was used to verify the thyroid hormone metabolism related MI in each cycle. The level of M RNA in cro RNAs and the determination of the level of D1 and TR beta in the liver of mice were measured by M RNA level.Western blot in the liver of type I deiodine (D1) and thyroid hormone receptor beta (TR beta), and the level of M RNA in the lipid metabolism related genes. Results: the content of triglyceride (TG) and total cholesterol (TC) was analyzed. Results: when high fat diet was fed for 7 weeks, the weight of group DIO was more than 1.2 times higher than that of group C, and the standard of obesity was successful, while the weight of C group and DIO-R group had no significant difference (P0.05). According to the sequencing results, the difference tables of liver in three groups of mice were screened. The micro RNAs: target that can function in the thyroid hormone metabolism acts on the MI R-383 of the D1 translation process. When the target is fed on the MI R-34a and MI R-146b. high fat diet of the TR beta transcriptional process, the levels of the DIO group and the DIO-R group are lower than those in the group. The level of D1 protein and FAS expression in the liver were significantly higher than that of the DIO-R group, while the expression of M RNA and protein level and CPT1 a, PGC1 alpha and CYP7A1 in TR beta was significantly lower than that of the DIO-R group (P0.05), but there was no significant difference between the two groups. During the period (17 weeks), the expression of MI R-383, MI R-34a and MI R-146b in the liver of the group DIO was significantly higher than that in the DIO-R group, and the expression of D1, TR beta and plasma T3 were significantly lower than that in the DIO-R group. The body weight, plasma TG level and TC level were significantly higher than that in group DIO-R (P0.05). In the late stage of high fat diet (27 weeks), the MI R-383 in the liver of DIO group was significantly higher than that in the DIO-R group. The level of D1 in the liver and the level of T3 in the liver were significantly lower than that in the DIO-R group (P0.05). The expression of the liver in the three groups of mice was no more than that of the DIO-R group. The weight of the significant difference (P0.05) group.DIO, the expression of FAS, the content of TG, TC and LDL-C were significantly higher than that of the DIO-R group (P0.05). The correlation analysis showed that the level of MI R-383 and D1 protein in the liver was negatively correlated (P0.05), and there was a significant negative correlation between the liver and the level of the egg white. There was a significant negative correlation between the level of RNA and the protein level (P0.05). The content of TG and TC in the liver was significantly positively correlated with the content of TG and TC in the plasma (P0.05), MI R-146b was positively correlated with the TG and TC content in plasma, but was not significant (P0.05). 5) conclusion: the effect of high fat diet feeding on the expression of thyroid hormone metabolism related micro RNAs in the liver of DIO-R and DIO mice was different in different cycles. Compared with the DIO-R group, the expression of MI R-383 in the liver of early DIO mice was inhibited, and the expression of D1 in the liver was increased, while high fat diet was used in the middle and late stage of high fat feeding. The expression of MI R-34a and MI R-146b in the liver of the DIO group increased, making the expression of TR beta in the liver inhibited mi R-383 in the liver of the.DIO-R and DIO mice, and the difference in the expression of the lipid metabolism related genes in the target gene. The difference between obesity and obesity resistance phenotypes.
【學位授予單位】：江南大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R589.2

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本文編號：1963958