【摘要】：目的:肥胖是由于能量攝入和能量消耗的長(zhǎng)期不平衡造成的,然而因高能量攝入?yún)s產(chǎn)生肥胖抵抗的現(xiàn)象的個(gè)體在人群和不同動(dòng)物種類中都普遍存在,但其發(fā)生機(jī)制尚不明確。因此,本研究采用C57BL/6J小鼠建立高脂飲食誘導(dǎo)的肥胖動(dòng)物模型(Diet-induced obesity,DIO)和肥胖抵抗動(dòng)物模型(Diet-induced obesity resistance,DIO-R),探討棕色脂肪組織的非顫性產(chǎn)熱功能變化在高脂飲食誘導(dǎo)肥胖或肥胖抵抗中的作用及機(jī)制。方法:選取8周齡健康雄性C57BL/6J小鼠,隨機(jī)分成低脂飲食組(LFD)和高脂飲食組(HFD),在自由進(jìn)食和飲水條件下,低脂組小鼠喂養(yǎng)低脂飼料,高脂飲食組喂養(yǎng)高脂飲食,每周記錄體重。喂養(yǎng)至第10周時(shí),高脂飲食組小鼠體重顯著高于低脂對(duì)照組(≥Mean+3SD)者定義為肥胖敏感小鼠;高脂飲食喂養(yǎng)后體重仍低于上述標(biāo)準(zhǔn)者(Mean+3SD)定義為肥胖抵抗小鼠。第11周測(cè)定各組小鼠每日進(jìn)食量,每類小鼠隨機(jī)分出一組進(jìn)行急性冷刺激處理(4℃,6小時(shí))后處死,收集棕色脂肪組織(Brown adipose tissue,BAT)和皮下脂肪組織(Subcutaneous adipose tissue,SAT),采用HE染色觀察各組織脂肪細(xì)胞形態(tài)、脂質(zhì)沉積程度;Real-time PCR檢測(cè)脂肪組織目標(biāo)基因表達(dá)水平(UCP1,PGC-1αand PRDM-16),免疫組織化學(xué)染色觀察皮下脂肪組織UCP-1表達(dá)情況。結(jié)果:高脂喂養(yǎng)第10周,根據(jù)體重與低脂對(duì)照組比較結(jié)果,將高脂飲食組分為DIO鼠與DIO-R鼠。檢測(cè)其連續(xù)五天進(jìn)食量顯示,DIO鼠與DIO-R鼠平均每日能量攝入量均顯著高于對(duì)照組。對(duì)脂肪組織的HE染色后觀察發(fā)現(xiàn),與低脂組相比,無(wú)論是常溫下還是冷刺激6小時(shí)后,DIO鼠BAT與SAT中可觀察到大脂肪空泡與更大的脂肪細(xì)胞輪廓,明顯大于對(duì)照組與DIO-R鼠;DIO-R鼠BAT與SAT和低脂組相比,無(wú)論是常溫下還是冷刺激6小時(shí)后,都無(wú)明顯差異;在BAT中,DIO鼠在常溫下ucp-1的m RNA水平高于低脂組,在急性冷刺激下,ucp-1表達(dá)水平并沒(méi)有發(fā)生改變,而DIO-R鼠無(wú)論是在常溫下還是冷刺激下UCP-1的表達(dá)水平明顯上調(diào),且DIO-2的m RNA表達(dá)水平明顯高于其他組;常溫下和冷刺激下,DIO-R鼠Prdm-16的m RNA表達(dá)水平高于低脂組;在冷刺激下,對(duì)照組與DIO組都有很明顯的增高,而DIR鼠并沒(méi)有發(fā)生變化。在SAT中,無(wú)論常溫下還是冷刺激下,DIO-R鼠的UCP-1表達(dá)水平明顯高于對(duì)照組和DIO鼠;其次DIO-R鼠的PGC-1α基因m RNA表達(dá)水平與UCP-1表達(dá)相一致,無(wú)論是常溫還是冷刺激下,都是明顯高于對(duì)照鼠和DIO鼠;而DIO鼠中PGC-1α基因m RNA表達(dá)水平是低于正常鼠;無(wú)論是常溫還是冷刺激下,DIO與DIR鼠的Prdm-16基因的m RNA表達(dá)高于對(duì)照組;常溫下,DIO-R鼠DIO-2基因m RNA表達(dá)水平高于對(duì)照組和DIO鼠。其次是免疫組化結(jié)果,與DIO-R鼠皮下脂肪ucp-1的m RNA相一致,無(wú)論是冷刺激還是常溫,DIO-R鼠皮下脂肪ucp-1表達(dá)明顯高于其他組。結(jié)論:本研究結(jié)果提示棕色脂肪組織非顫性產(chǎn)熱功能的增強(qiáng)及皮下脂肪組織“米色化”水平的提高是高脂飲食誘導(dǎo)肥胖抵抗小鼠保持較小體重增加的一個(gè)重要原因,具體的機(jī)制有待進(jìn)一步探索。
[Abstract]:Objective: obesity is caused by the long-term imbalance of energy intake and energy consumption. However, individuals who produce obesity resistance due to high energy intake are common in both population and different animal species, but their mechanism is not clear. Therefore, this study uses C57BL /6J mice to establish high fat diet induced obese animal models. Diet-induced obesity (DIO) and obesity resistant animal model (Diet-induced obesity resistance, DIO-R), explore the role and mechanism of the change of non tremor heat producing function of brown adipose tissue in high fat diet induced obesity and obesity resistance. Methods: 8 Zhou Lingjian healthy male C57BL/6J mice were selected and randomly divided into low fat diet group (LFD) and high In the fat diet group (HFD), low fat diet group was fed low fat diet and high fat diet group was fed a high fat diet, and the weight was recorded every week in the low fat diet group. The body weight of the high fat diet group was significantly higher than that of the low fat control group (> Mean+3SD) in the high fat diet group at tenth weeks. The standard person (Mean+3SD) was defined as a obese resistance mouse. The daily intake of diet was measured in each group of mice in eleventh weeks. Each group was randomly assigned to death after acute cold stimulation (4, 6 hours), and the brown fat tissue (Brown adipose tissue, BAT) and subcutaneous fat tissue (Subcutaneous adipose tissue, SAT) were collected and observed by HE staining. The morphology of adipocyte and the degree of lipid deposition in each tissue; Real-time PCR was used to detect the expression level of target gene of adipose tissue (UCP1, PGC-1 alpha and PRDM-16). The expression of UCP-1 in subcutaneous adipose tissue was observed by immunohistochemical staining. Results: high fat feeding was used for tenth weeks, and the high fat diet group was divided into DIO mice and D groups according to the results of weight and low fat control group. The average daily intake of IO-R mice for five days showed that the average daily energy intake of both DIO and DIO-R mice was significantly higher than that in the control group. After HE staining of adipose tissue, compared with the low fat group, the large fat vacuoles and larger adipocyte silhouette could be observed in BAT and SAT in DIO rats, no matter at normal temperature or 6 hours of cold stimulation. Compared with the control group and the DIO-R rat, the BAT of the DIO-R rat was not significantly different from the SAT and low fat groups for 6 hours at normal temperature or cold stimulation. In BAT, the m RNA level of DIO rats at normal temperature was higher than that of the low fat group. The expression level of UCP-1 did not change under the acute cold stimulation, while the DIO-R rats were at normal temperature or cold stings. The expression level of UCP-1 was obviously up-regulated, and the expression level of M RNA in DIO-2 was significantly higher than that in other groups. The m RNA expression level of Prdm-16 in DIO-R rats was higher than that in low fat group under normal temperature and cold stimulation. Under cold stimulation, the control group and DIO group were significantly higher, while DIR mice did not change. In SAT, under normal temperature or cold stimulation, The expression level of UCP-1 in DIO-R rats was significantly higher than that of the control and DIO mice, and the m RNA expression level of the PGC-1 a gene in the second DIO-R mice was the same as that of the UCP-1 expression. Both the normal and the cold stimuli were significantly higher than those of the control rats and DIO mice. The expression of M RNA in the Prdm-16 gene of DIR mice was higher than that in the control group. At normal temperature, the expression level of M RNA of DIO-2 gene in DIO-R rats was higher than that of the control group and the DIO rat. The results suggest that the enhancement of the non tremor function of the brown adipose tissue and the improvement of the "Beige" level of the subcutaneous adipose tissue are an important reason for the high fat diet to induce the weight gain of the obese resistance mice, and the specific mechanism needs to be further explored.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R589.2

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