過多的脂肪堆積在肝臟中,輕者會造成脂肪肝,重者還會導致脂肪性肝臟發炎(steatohepatitis)、肝臟纖維化(liver fibrosis)及肝硬化(liver cirrhosis)。而脂肪肝又會牽涉到許多代謝疾病(metabolic syndrome),如高血壓(hypertension)、高血脂症、高膽固醇症、糖尿病,因此開發具化學預防或治療成分的天然物,嚴然成為目前預防或治療脂肪肝性疾病重要的研究方向。桑椹萃取物已被證實具有降血脂及抗粥狀動脈硬化等疾病之成效,因此本篇欲進一步探討桑椹萃取物對抑制肝臟脂肪堆積是否也有相似之功效。本論文以細胞模式和動物模式探討桑椹萃取物對於減少肝臟脂肪堆積之作用與機制,分別以油酸和高油脂飲食 (high fat diet, HFD) 誘導細胞實驗及動物之肝臟脂肪堆積。結果證實桑椹萃取物確實可降低血液和肝臟脂質 (三酸甘油脂、膽固醇、脂肪酸) 堆積的現象,並使高油脂飲食組動物體重增加情形趨緩。亦發現桑椹萃取物能降低脂質生成酵素及其轉錄因子之表現,例如FAS、ACC、HMGCoR、GPAT、SREBPs等,並使促進脂質代謝酵素及其轉錄因子之表現,如CPTI、PPARα,達到降低肝臟脂質堆積的效果。本研究推論,桑椹萃取物主要是透過AMPK (AMP-activated kinase) 之傳訊路徑調控上述這些蛋白質,達到降低肝臟脂肪堆積之效果。研究結果顯示桑椹萃取物對於開發成為預防及治療脂肪肝的保健食品具有相當的潛力。
Excess fat accumulated in the liver, the lighter will cause fatty liver, the serious one will also cause steatohepatitis, liver fibrosis and liver cirrhosis. Fatty liver will involve a lot of metabolic syndrome, such as obesity, hypertension, dyslipidemia and diabetes. Therefore, develop the natural thing with chemistry preventing or treatment composition has already become an important direction for treat the fatty liver disease. Mulberry extracts (MWE、MAE and MPE) have been known to reduce blood lipid and prevent atherosclerosis. However, the effects of mulberry extracts on regulating hepatic lipid metabolism are unclear. To better understand the functions and mechanisms of mulberry extracts in reducing hepatic lipid accumulation, the fat overload conditions both in cell culture and an animal experimental model were performed. In this study, mulberry extracts were further confirmed that they could regulate serum and hepatic lipid contents (e.g. triglyceride, cholesterol, and free fatty acid) and reduce the rate of body weight in mice. Furthermore, mulberry extracts also could decrease the expression of lipogenic enzymes, such as FAS, ACC, HMG-CoA reductase, SREBP, GPAT and increase the expression of CPTI and PPARα proteins, which are critical regulators of hepatic lipid metabolism. The results show that mulberry extracts are able to reduce the hepatic lipid accumulation through the AMPK (AMP-activated protein kinase) signaling pathway. These observations suggested that mulberry extracts have potentiality in developing the health food for preventing and remedying fatty liver.