請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/94741
標題: 大花咸豐草萃取物經由GATA-3調控CRT來抑制3T3-L1前脂肪細胞脂質生成
作者: 張以芳
關鍵字: 大花咸豐草萃取物
脂質生成
出版社: 獸醫學系暨研究所
摘要: 第二型糖尿病及心血管疾病等代謝性疾病常會併發肥胖,而開發減肥藥一直存在著安全與藥效相互衝突的問題,因此從天然物中篩選安全又能調控脂質代謝的化合物,逐漸成為調控脂質代謝藥物開發的首選。Calreticulin (CRT)為內質網中的鈣離子攜帶蛋白,負責細胞內鈣離子恆定,及活化下游因子Calcineurin (CaN)來抑制脂肪細胞的分化。本實驗室首先利用大花咸豐草萃取物的polyacetylene 成分Cytopiloyne (CP)研究影響CRT調控脂肪細胞的分化。我們將3T3-L1前脂肪細胞培養在含有誘導分化因子3-isobutyl-1-methylanthine(IBMX)、Dexamethasone (DEX)、Insulin培養液中,發現CP能夠抑制脂肪細胞分化及降低分化指標PPARγ、C/EBPα、aP2、adiponectin的表現;接著利用Western blotting及電生理技術,證明CP能增加CRT表現及胞內鈣濃度;並利用CaN抑制劑FK506確定CP是透過CRT途徑來調控脂肪細胞分化;我們更進一步使用SiRNA技術發現CP是藉由GATA-3來調控CRT表現。此研究說明CP為一藉由新機制來調控脂肪細胞分化的新穎結構。 There is a lot of metabolism disease could cause obesity, like type 2 diabetes and cardiovascular disease. It is always existing conflict between safety and efficacy in developing anti obesity drugs. Extract herbal compounds which inhibited adipogenesis with safty are gradually become the priority choice of anti obesity drugs developing. Calreticulin (CRT) is a major Ca2+ - buffering protein in the lumen of endoplasmic reticulum, which control intracellular calcium homeostasis and activate the calcineurin (CaN), a downstream factor of CRT, to inhibit the differentiation of adipocyte. We use cytopiloyne (CP), a polyacetylene of Bidens pilosa, to confirm the anti adipogenesis effect through regulate CRT expression in adipocyte. First, we culture the 3T3-L1 preadipocyte in the medium, which is containing induced differentiation factor, 3-isobuty-1-methulanthine (IBMX), dexamethasone (DEX) and insulin. We find that CP can inhibit the differentiation of adipocyte and get lower adipogenic marker expression, such as PPARγ, C/EBPα, aP2, adiponectin. Then, use western blotting and electrophysiology to prove that CP can increase CRT expression and intracellular calcium concentration. FK506, a CaN inhibitor, reversed the anti-adipogenesis effect on CP incubated 3T3-L1 preadipocyte. These results confirmed that CP inhibited adipogenesis through CRT pathway. Finally, a GATA-3 siRNA experiments indicated that CP enhance CRT expression was GATA-3 dependent. This study shows that CP is a novel phytocompound, which offered a new anti-adipogenesis mechanism.
URI: http://hdl.handle.net/11455/94741
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