Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/20301
標題: 發酵產物對於瘦體素基因刪除鼠透過餵食高脂飼料所誘導脂肪肝症狀之影響
The effects of fermented products on high fat diet-induced fatty liver syndrome in leptin-defective knockout mice
作者: 蔡至倫
Tsai, Chih-Lun
關鍵字: ob/ob肥胖鼠
ob/ob mice
非酒精性脂肪肝
脂肪合成基因
HepG2肝癌細胞株
non-alcoholic fatty liver disease
lipid synthesis gene
HepG2 livr cancer cell line
出版社: 生命科學系所
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摘要: 脂肪肝係指肝臟內蓄積的脂肪含量超過肝臟重量5% 者稱之。在病因上主要分為酒精性脂肪肝 (AFLD)及非酒精引起的脂肪肝 (NAFLD)。後者大多為肥胖、胰島素阻抗、第二型糖尿病所引起。根據最新的研究指出,非酒精性脂肪肝盛行率約為16-23%。而有相當比例會慢慢地變成肝纖維化、肝硬化、肝炎甚至是肝癌的發生,至今仍無確切有效之治療藥物。本研究利用瘦體 (leptin)被刪除的ob/ob肥胖鼠並餵食60%高脂飼料,作為非酒精性脂肪肝動物模式,以六週齡大的小鼠進行實驗,管餵處理發酵產物(fermented product) (140 mg/kg of body weight per day),分為四組: (1) ob/ob小鼠+ ddH2O肥胖控制組、(2) ob/ob小鼠+ fermented product處理組、(3) WT小鼠+ ddH2O 正常控制組、與 (4) WT小鼠+ fermented product處理組 (n=6),實驗進行四個星期。從實驗結果可知,餵食發酵產物之ob/ob肥胖鼠處理組相較ob/ob肥胖鼠餵食去離子水控制組,無論在肝臟脂肪外觀、H&E染色與油紅染色等結果,及肝臟油滴堆積情形,都有明顯減少與改善的情況,且肝臟中三酸甘油酯與膽固醇含量也有下降的趨勢 (p<0.05);此外,我們發現ob/ob肥胖鼠餵食發酵產物處理組相對於ob/ob肥胖鼠餵食去離子水控制組,脂肪合成途徑的三個調控基因,包括sterol regulatory element-binding protein-1 (SREBP-1)、 fatty acid synthase (FAS) 與 acetyl-CoA carboxylase (ACC)表現量明顯較低 (p<0.05); 而以濃縮純化後之發酵產物處理經脂肪酸 (fatty acid)誘導HepG2肝細胞累積細胞內油滴,其三個脂肪合成基因的mRNA表現量也有顯著降低 (p<0.05)。因此我們推測發酵產物可藉由抑制脂肪合成基因路徑,抑制肝臟脂肪堆積,進而改善非酒精性脂肪肝徵狀,基於以上理由,我們認為此發酵產物具有開發為治療與預防非酒精性脂肪肝之功能成份的潛力。
Fatty liver disease has been defined as intrahepatic triglyceride (IHTG) content >5% of liver volume or liver weight in animal or human being. Fatty liver is commonly associated with obesity, insulin resistance, and diabetes. It is estimated that about 16-23% of population exhibits the syndrome of the non-alcoholic fatty liver disease (NAFLD) in world wide. Severe fatty liver is sometimes accompanied by steatohepatitis or develop hepatocellular carcinoma. To date, there is still no effective therapy to treat NAFLD, so the focus of current investigations has been on the development of effective components or functional products with bioactivities. In this study, we used leptin gene knockout ob/ob mice as a NAFLD animal disease model. Six-week-old ob/ob mice were administered with fermented product (140 mg/kg of body weight per day) for four weeks. Four experimental groups were designed as followed: (1) ob/ob mice treated with ddH2O group, (2) ob/ob mice treated with fermented product group, (3) WT mice treated with ddH2O group, and (4) WT mice treated with fermented product group (n=6). After oral administration, fermented product treatment improves fatty liver syndrome by inhibiting liver lipogenesis gene expression, and decreasing the contents of cholesterol and triacylglyceride (TG) in liver (p<0.05). In addition, the result showed that treatment with fermented product has significantly reduced oil drops in liver tissue examed by H&E stain and oil red stain. Furthermore, we found that fermented product treatment with ob/ob mice markedly decreased the expression of sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) gene that was an effect on reducing lipogenesis gene (p<0.05). Fatty acid-riched HepG2 cell culture treated with the peptide fractions from fermented product also decrease lipogenesis gene expression. We speculated that fermented product improve the NAFLD throught the inhibition of lipogenesis pathway. In conclusion, our data suggested that peptides derived from fermented product may have potentials for clinical applications in the prevention or treatment of NAFLD.
URI: http://hdl.handle.net/11455/20301
其他識別: U0005-2408201214474800
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2408201214474800
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