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標題: Lucidone作用於抑制脂質新生及減緩高油脂飼料造成的肥胖與代謝失調之效果
Effects of lucidone on suppressing adipogenesis and attenuating obesity and consequent metabolic disorders in high-fat diet mice
作者: 謝瑀心
Hsieh, Yu-Hsin
關鍵字: 紅果釣樟;Lindera erythrocarpa Makino;脂質新生;高油脂飼料誘導肥胖;Adipogenesis;Diet-induced obesity
出版社: 生物科技學研究所
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The incidence of obesity has increased dramatically worldwide over the last few decades because of the life style changes. Obesity is associated with an increased risk of a spectrum of diseases, including malignancy, heart disease, cerebrovascular disease, type 2 diabetes, hypertension, hyperlipidemia and others. In this study, we investigated the effects of lucidone, an extract from the fruit of Lindera erythrocarpa Makino, in vitro on anti-adipogenesis in 3T3-L1 cells and in vivo on high-fat diet (60% energy from fat) induced obesity in C57BL/6 mice. Our data showed that lucidone suppressed adipogenesis in 3T3-L1 cells in a dose dependent manner and reduced the transcriptional levels of several adipogenic genes, including PPAR-gamma, C/EBP-alpha, LXR-alpha, LPL, aP2, GLUT4 and adiponectin, without affecting cell cycle. A group of 5-week-old male C57BL/6 mice fed a high-fat diet supplemented with lucidone at a dosage of 138.75 mg/kg for 12 weeks showed lowered body and liver weights, decreased food efficiency, and lowered levels of serum cholesterol, TG, glucose and insulin. Dissection of adipose tissue from lucidone-fed mice showed reductions in the average and proportions of fat-cell size. At the molecular level, the adipocytic GLUT4 and CD36 levels were induced by dietary lucidone that may contribute to the improvement of insulin sensitivity, hyperglycemia and hyperlipidemia. Adiponectin, which was highly induced in LSH/H mice, may be a vital factor that promotes energy expenditure and alleviates body weight gain. Moreover, systemic analysis of hepatic gene expression profile showed that dietary lucidone modulates some gene expression involved in lipid and glucose metabolism. Taken together, this study reveals the potential of lucidone as a nutraceutical for preventing obesity and consequent metabolic disorders under unhealthy eating habits.

由於人們生活及飲食習慣的改變,已開發國家的肥胖人口數量在過去幾十年間正急劇增加。肥胖已知會提高罹患多種疾病的風險,包括惡性腫瘤、心臟病、腦血管疾病、第二型糖尿病、高血壓和高血脂等等。在本篇研究中,我們選擇來自紅果釣樟(Lindera erythrocarpa Makino)果實的活性成分lucidone作為目標天然物,在體外試驗中發現lucidone能夠在不影響細胞週期的情況下有效抑制脂質新生,且其效果與劑量呈現正相關;進一步分析其分子層次的影響發現lucidone能夠抑制多種參與脂質形成之基因的表現量,包括PPAR-gamma, C/EBP-alpha, LXR-alpha, LPL, aP2, GLUT4 以及adiponectin。體內試驗方面,持續十二週以高油脂飼料餵食五週齡C57BL/6之雄性小鼠並同時補充lucidone (138.75毫克/每公斤體重),相較於單純餵食高油脂飼料之控制組,攝取lucidone明顯減緩小鼠的體重變化,減少肝臟及脂肪組織重量,降低飼料效率,以及減少血液中的膽固醇、三酸甘油脂、胰島素及血糖濃度。脂肪組織之切片顯示,餵食lucidone能夠有效降低脂肪細胞的平均大小及其分佈比例。分子層次上,lucidone能夠誘導脂肪組織的GLUT4和CD36之表現,此現象可能有助於提高胰島素的敏感性,改善高血糖和高血脂的狀況。同時,lucidone明顯誘發adiponectin的表現量,此現象可能在提高能量代謝上扮演一定之重要的角色,藉以降低體內的能量儲存進而減緩體重增加。最後,我們利用微陣列分析lucidone對肝臟基因表現的影響,發現其影響不同基因參與脂質及糖類代謝的多條生化途徑,包括膽固醇生合成、脂肪酸合成、脂肪酸氧化作用。綜合以上發現,本篇研究顯示lucidone具有相當高的潛力開發為植物藥,應用於預防不健康飲食習慣所造成的肥胖,進而改善由肥胖所引發的代謝功能失調。
其他識別: U0005-2808201310005800
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