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標題: | 探討中國橄欖水萃物對高脂飲食或高脂飲食合併STZ誘導代謝異常小鼠之肥胖與胰島素敏感性的影響 The effects of Chinese olive water extract on obesity and insulin sensitivity in C57BL/6 mice under high-fat diet treatment with or without STZ |
作者: | Chia-Yu Lin 林佳諭 |
指導教授: | 謝淑貞 |
關鍵字: | 高脂飲食,肥胖,胰島素阻抗,脂肪新生,脂質合成, high fat diet,obesity,insulin resistance,adipogenesis,lipogenesis, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 肥胖是因能量攝取和消耗間不平衡,造成脂肪組織的脂質過度累積,進而導致體內脂質代謝異常,而肥胖目前已是全世界盛行的代謝失調疾病。脂質堆積主要有兩種型態:脂肪細胞增生(hyperplasia)與脂肪細胞肥大(hypertrophy)。脂肪細胞數目增加,需經脂肪新生 (adipogenesis),分化成成熟的脂肪細胞。在成熟脂肪細胞內,脂質累積受到脂質合成(lipogenesis)與脂解作用(lipolysis)的調控。脂質過度堆積則會導致脂肪細胞發炎並產生局部胰島素阻抗,增加釋出游離脂肪酸,對肝臟與肌肉組織造成脂肪毒性,進而導致空腹血糖異常、高胰島素血症等全身性胰島素阻抗病徵。中國橄欖富含多酚類化合物,以沒食子酸 (gallic acid) 及鞣花酸 (ellagic acid)為主,並具護肝、抗氧化、抗發炎等生物活性,然而其改善肥胖及胰島素阻抗之功效與可能機制尚未明瞭。因此本研究將以高脂飲食或高脂飲食合併低劑量STZ誘導之C57BL/6小鼠,探討中國橄欖水萃物(COE)的介入對於肥胖與胰島素敏感性的影響,結果顯示COE的介入具有減少小鼠體重、附睪脂肪脂質堆積與改善空腹血糖上升之效果。而脂肪組織基因表現結果顯示,COE的介入會減少脂肪新生相關(C/ebpα、Pparγ、Srebp-1c)與脂質代謝相關(Fas、Scd-1、Dgat等)基因mRNA表現量;亦減少ACC和FAS之蛋白質表現。代謝異常小鼠上升之空腹血糖、血中胰島素與HOMA-IR等胰島素抗性指標於COE介入後顯著降低,而初步結果也顯示給予COE的小鼠骨骼肌細胞膜上葡萄糖轉運蛋白(GLUT4)有較高的表現。綜合以上,我們推測COE可能透過干擾動物脂肪組織之脂肪新生、減少脂質合成,並增加肌肉葡萄糖攝取能力,進而達到抗肥胖、改善高血糖與胰島素敏感性的效果。而3T3-L1前脂肪細胞實驗結果顯示COE的給予可減少脂肪細胞內油滴大小及分布面積。此外,長時間給予COE可抑制C/ebpα、Pparγ與Srepbp-1c mRNA表現,其中只有PPARγ蛋白質表現量在長時間處理COE後減少。然而,COE對脂肪新生轉錄因子蛋白質表現量之影響與mRNA表現或表觀結果之影響不一致的情形,我們推測可能有其他轉譯後層次的調控機制參與干擾脂肪新生。 Obesity results from the unbalance of energy intake and expenditure, which leads to lipid over-accumulation in adipose tissues, and then it impairs the lipid metabolism in the body. Nowadays, obesity has become one of the most prevalent metabolic diseases in the world. There are two major types of lipid accumulation:adipocyte hyperplasia and adipocyte hypertrophy. The increase in cell number requires adipogenesis, a process of preadipocyte differentiating into mature adipocyte. In mature adipocyte, lipid accumulation is regulated by lipogenesis and lipolysis. Obesity causes inflammations in adipose tissue, leading to local insulin resistance and an increased flux of free fatty acids from adipocytes to other tissues. Increased flux of free fatty acid leads to lipotoxicity in the liver and muscle, which contributes to systemic insulin resistance with impaired fasting blood glucose and hyperinsulinemia. Chinese olive contains high contents of polyphenolic compounds, among which gallic acid and ellagic acid are the most dominant ones. Moreover, it has been reported to have many bioactivities, including hepatoprotective, anti-oxidative, and anti-inflammatory effects. However, whether it could improve the complications of obesity as well as insulin resistance, and its possible mechanisms remain unknown. Hence, the aims of recent study is to investigate the ameliorative effects of chinese olive water extract (COE) on obesity and insulin sensitivity in C57BL/6 mice under high-fat diet (HFD) treatment with or without streptozotocin (STZ). COE could markedly reduce the increased body weight and epididymal white adipose tissue (eWAT) mass. In addition, COE decreased the symptoms of insulin resistance, including fasting blood glucose, plasma insulin levels, and HOMA-IR. We further demonstrated that COE not only downregulated the mRNA levels of adipogenesis- related (C/ebpα, Pparγ, and Srebp-1c) and lipid metabolism-related (Fas, Scd-1, Dgat, etc.) genes, but also suppressed the protein levels of ACC and FAS in eWAT. It was found that an increase in the protein expression of glucose transporter (GLUT4) on skeletal muscle cell membrane under COE supplement. Taken together, it seems that COE may improve obesity, hyperglycemia, and insulin sensitivity through interfering with adipogenesis, inhibiting lipogenesis in eWAT, and increasing glucose uptake in muscle. In 3T3-L1 preadipocytes, COE reduced the size and distribution of lipid droplets. The mRNA levels of C/ebpα, Pparγ, and Srepbp-1c genes were down-regulated, while only the protein expression of PPARγ was decreased under long-term administration of COE. However, inconsistency between the effect of COE on the expression of adipogenic transcription factors and that on the expression of adipogenic transcription factor genes or fat mass reduction allow us to infer that there might be some post-translational regulation mechanisms involved in interfering with adipogenesis. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70477 |
DOI: | 10.6342/NTU201803161 |
全文授權: | 有償授權 |
顯示於系所單位: | 食品科技研究所 |
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