肥胖，為體內脂肪過度累積造成的現象，雖不是疾病，但卻與人體許多疾病密切相關。本研究目的在於探討遠志與冬瓜皮萃取物是否具有抑制脂肪累積之功效。我們使用3T3-L1脂肪細胞與高脂飼料誘發小鼠肥胖，進行抑制脂肪累積功效實驗，並透過次世代基因定序方法，分析小鼠肝臟基因表現與腸道菌相分布，進而了解兩種萃取物抑制脂肪累積之可能機轉。透過細胞實驗證實，遠志與冬瓜皮萃取物皆具有抑制脂肪生成、降低三酸甘油脂含量與促進脂肪脂解酶活性，且不具有細胞毒性。活體實驗證實，高脂飼料誘發肥胖鼠於餵食遠志或冬瓜皮萃取物五周後，其體型外觀、體重增加量、三酸甘油脂含量與肝臟損傷程度，皆有明顯改善現象。進一步透過分析各組小鼠肝臟基因表現，相較於僅餵食高脂飼料組小鼠，發現餵食遠志與冬瓜皮萃取物五周後，小鼠肝臟參與脂肪與膽固醇合成代謝的基因表現量皆有明顯改變。遠志萃取物具有促進轉錄因子PPARα基因表現，顯示其具有促進脂肪分解的功效，同時，遠志萃取物亦抑制發炎因子IL-1β基因表現，顯示其具有降低因肥胖造成慢性發炎反應的功效。冬瓜皮萃取物抑制脂肪累積的機轉則與遠志不盡相同，冬瓜皮萃取物主要改變參與膽汁合成的基因表現。此外，實驗發現兩種萃取物皆具有改變腸道菌相的效果，相較於僅餵食高脂飼料組別，遠志與冬瓜皮萃取物皆可提高 Bacteriodetes / Firmicutes細菌比例，同時亦可增加Proteobacteria 細菌與減少 Deferribacteres細菌數量。根據這些實驗結果，遠志與冬瓜皮萃取物，兩者皆具有開發為抑制脂肪累積之保健品或藥物的潛力。

Obesity, an excessive accumulation of lipid in the body, is closely associated with many important human disorders. The aim of this study is to investigate whether a Polygala tenuifolia extract (PTE) or a Benincasa hispida extract (BHE) possesses an anti-obesity activity and how it affects liver gene expression and gut microbiota. We used 3T3-L1 adipocytes and a high-fat diet-induced obesity mouse model to determine the effects of these extracts on lipid accumulation. Next generation sequencing analysis of liver gene expression and gut microbiota profiles on both of the treatments were conducted to elucidate the possible mechanisms. Treatment of fully differentiated 3T3-L1 adipocytes with either PTE or BHE inhibited lipid accumulation through reducing lipid formation and triglyceride content, and increasing lipase activity. No cytotoxicity was observed by both treatments. After 5 weeks of both treatments, the weight gain, serum triglyceride content and liver steatosis in the high fat diet-induced obese mice were all reduced. Liver transcriptomic analysis revealed that expression of genes involved in lipid and cholesterol metabolism was altered significantly. PTE inhibited lipid accumulation via inducing the expression of the master transcription factor PPARα and attenuating the chronic inflammation of the obesity. On the other hand, BHE inhibited lipid accumulation via regulating bile acid synthesis or composition. In addition, treatment with PTE and BHE elevated the Bacteriodetes/Firmicutes ratio in the gut, enriched the Proteobacteria population and reduce the Deferribacteres populations. These results indicate that both PTE and BHE have potential to be developed into anti-obesity food supplements and therapy.

中文摘要.................2
Abstract................3
Introduction............5
Materials and Methods..11
Results................19
Discussion.............48
Conclusion.............54
References.............57
Additional files.......68

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