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標題: | 山苦瓜對睪丸剔除小鼠之不同區塊脂肪組織的雄激素效應 The Depot-specific Androgen-like Effects of Wild Bitter Gourd on the Adipose Tissues of Orchidectomized Mice |
作者: | Yu-Jen Wang 王昱仁 |
指導教授: | 黃青真(Ching-Jang Huang) |
關鍵字: | 山苦瓜,睪丸剔除,雄激素受器,脂肪組織區塊差異,褐化, wild bitter gourd,castration,androgen receptor,WAT depot difference,browning, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 已知雄激素可以透過其受器 (Androgen Receptor, AR) 影響脂肪組織。流行病學及臨床研究結果顯示,缺乏或是較低雄激素濃度與代謝異常相關。唯雄激素缺乏動物模式實驗,卻有正反兩面不同之結果。本實驗室過去的研究,觀察到飲食補充山苦瓜全果凍乾粉 (BGP) 可促進小鼠白色脂肪組織褐化,並且在細胞模式中發現BGP萃物可活化AR。
本實驗旨在探討在缺乏內源性雄激素的狀況下,山苦瓜如何影響脂肪組織的代謝調節和基因表現,以及其對於不同區塊脂肪組織 (depot) 的效應。我們使用經過睪丸剔除手術 (Castration, Cast) 或假手術 (Sham) 的C57BL/6J公鼠,餵食高蔗糖飼料 (以AIN-93G飼料調整,含50% w/w 蔗糖)共23週,其中睪丸剔除鼠分為不補充 (Cast組)、飲食補充5% BGP (Cast+BGP) 或0.007%丙酸睪固酮 (Cast+TP)等三組。 經過23週試驗飼料餵食後,Cast+BGP組的體重顯著輕於Cast組及Sham組,而後兩組之間沒有統計差異。Cast+BGP組之鼠蹊部皮下脂肪 (Inguinal White Adipose Tissue, IWAT) 以及腎周圍脂肪 (Retroperitoneal White Adipose Tissue, RWAT) 之絕對重量與相對重量,均顯著低於Cast組。Cast+BGP組與Cast+TP組之攝食效率與能量效率顯著低於Sham 與Cast組。Sham組比起Cast組有顯著較高的血清三酸甘油酯,而Cast+BGP則是顯著的低於Sham組與Cast+TP組。而胰島素與總膽固醇方面,去除睪丸的Cast、Cast+BGP、Cast+TP三組顯著的低於Sham組,且三組間無顯著差異。AR的下游基因,特別是Fkbp5,在各區塊脂肪組織中,Sham組有顯著比Cast組高的表現量。而Srebf1、Cd36也在各區塊中皆觀察到Sham組有比Cast組高的mRNA表現量。BGP+Cast組之RWAT Fkbp5、Srebf1、Cd36與副睪脂肪 (Epididymal White Adipose Tissue, EWAT) 之Ar、Igf1、Srebf1、Cd36表現量與Sham組無顯著差異。在RWAT與IWAT中,Ccl2的表現量都是Sham組顯著的高於去除睪丸的三組。此外,只有在RWAT中能觀察到Sham組有比Cast組顯著高的IL6和IL10 mRNA表現量。 BGP在不同的區塊脂肪組織有不同的影響。在RWAT中,Cast+BGP組有較Cast組高的Fkbp5 mRNA表現,但是卻在IWAT中有較低表現。同時,只在RWAT中看到BGP促進TNFα, IL6, IL4和IL10 mRNA表現的作用。只有在IWAT, Cast+BGP組比起Sham組有顯著較高的Ucp1 mRNA表現量,暗示BGP有促進此塊脂肪褐化之作用。但是卻只在RWAT中能夠有與Sham組無顯著差異的Ucp2表現。有關Adipogenesis的基因部分,相較於Cast組,補充BGP組有顯著較高RWAT Cebpα mRNA的表現量,以及較高EWAT中 Pparγ之表現量。此外,在EWAT中,Cast+BGP組有顯著小於Cast組的平均脂肪細胞大小。最後,我們所測量的BAT幾種基因表現在組間並沒有明顯的差異。 總結以上,我們發現對於不同脂肪組織區塊,從AR、脂質代謝、褐化、脂肪細胞分化及發炎等相關基因表現,雄激素的缺乏以及山苦瓜的給予有不一樣的效果。而從我們的結果看來,山苦瓜除了有透過AR之調控,也有其他非透過AR之調控機制。 It has been shown that androgen status can affect white adipose tissues (WAT) through the cognate receptor, androgen receptor (AR). Although epidemiological and clinical studies observed an association between metabolic disorder and hypogonadism, conflicting results have been reported in animal studies. Previous results in our lab showed that bitter gourd extract interacted with AR in vitro. This experiment was designed to examine effects of wild bitter gourd powder (lyophilized whole fruit powder of Momordica Charantia, BGP) on various WAT depots in androgen deficiency using the orchidectomized mouse model. Male C57BL/6J mice were sham-operated or castrated and fed a high sucrose diet (HS, modified from AIN-93G comprising 50% w/w sucrose). Castrated mice were supplemented without (Cast) or with 5% BGP (Cast+BGP) or 0.007% testosterone propionate (Cast+TP). After 23 weeks of feeding, the Cast+BGP group had significantly lower body weight than Sham and Cast groups, and the latter two groups did not differ. The Cast+BGP group also showed significantly lower RWAT and IWAT weights (absolute and relative) compared to the Cast group. Cast+BGP and Cast+TP groups had significantly lower feed efficiency and energy efficiency compared to Sham and Cast groups. Sham mice had significantly higher serum triglyceride (TG) than the Cast group, while the Cast+BGP group showed significantly lower TG than Sham and Cast+TP groups. Cast, Cast+BGP, and Cast+TP groups had comparable serum insulin and total cholesterol levels, which were significantly lower than those of the Sham group. The Sham group had significantly higher AR downstream gene expressions, especially Fkbp5, than that of the Cast group in all three WAT depots. The mRNA expressions of Srebf1 and Cd36 also tended to follow androgen status and showed higher level in the Sham group than in the Cast in all depots. The mRNA expressions of Fkbp5, Srebf1, Cd36 in the RWAT and that of Ar, Igf1, Srebf1, Cd36 in EWAT of the Cast+BGP group were comparable to those of the Sham group. In RWAT and IWAT, Ccl2 mRNA expression was significantly higher in the Sham group than in the Cast group, but higher IL6 and IL10 mRNA expressions in Sham group than in Cast group were only observed in RWAT. BGP exerted different effects on different depots. While the Cast+BGP group had significantly higher Fkbp5 mRNA expression in RWAT, this group showed down-regulation of this gene in IWAT, compared to the CAST group. BGP up-regulated TNFα, IL6, IL4 and IL10 mRNA expressions only in RWAT but not other depots. Ucp1 mRNA was up-regulated only in the IWAT of the Cast+BGP, compared to the Sham group, implying enhanced browning in this depot. On the other hand, Ucp2 mRNA of RWAT was up-regulated in the Cast+BGP group to a level comparable to that of the Sham group. As for adipogenic genes, the Cast+BGP group showed significantly higher mRNA expressions of Cebpα in RWAT and Pparγ in EWAT than those of the Cast group. This group also had significantly lower mean adipocyte sizes than Cast group. In conclusion, androgen deficiency and dietary BGP supplementation showed depot-specific impacts on mRNA expressions of genes related to AR signaling, adipogenesis, lipid metabolism and inflammation in the white adipose tissues. Based on our results, some of the BGP effect might be through AR, but others might not. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70877 |
DOI: | 10.6342/NTU201802497 |
全文授權: | 有償授權 |
顯示於系所單位: | 生化科技學系 |
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