- 學位論文
探討芝麻木質素的抗肥胖潛力：芝麻素和芝麻酚透過 PPARγ訊號傳遞調節脂肪生成之研究
Exploring the Potential of Sesame Lignans in Combating Obesity: The Study of Sesamin and Sesamolin, and their Modulation of Adipogenesis through PPARγ Signaling
摘要
本研究探討芝麻中兩種主要木質素-芝麻素和芝麻酚的抗肥胖機制。這兩種木質素存在於芝麻籽中，具有抗發炎、抗癌和神經保護活性，並對肝臟、心血管疾病和代謝症候群具有益處。儘管芝麻素和芝麻酚已有廣泛的研究，但針對它們在抗肥胖方面的作用機制仍缺乏深入的研究。因此，本研究旨在闡明芝麻素和芝麻酚對脂肪生成的調控作用，並以3T3-L1細胞作為模型系統並假設芝麻素和芝麻酚透過調節過氧化物酶體增殖物活化受體 γ (PPARγ) 抑制脂肪生成。本研究深入探討芝麻素和芝麻酚對脂質聚集、三酸甘油脂形成以及關鍵脂肪生成轉錄因子，包括 PPARγ 和 CCAAT/enhancer-binding protein alpha (C/EBPα)的表達量之效應。此外，本研究還探討有關芝麻素和芝麻酚對下游目標蛋白如脂肪酸結合蛋白4 (FABP4)、激素敏感性脂肪酶 (HSL)、脂蛋白脂肪酶 (LPL) 和葡萄糖轉運蛋白4 (GLUT4) 的影響。研究結果顯示，芝麻素和芝麻酚能夠依劑量降低脂肪分化、三酸甘油脂形成，以及 PPARγ 和 C/EBPα 的 mRNA 和蛋白質表達量。此外，經這些木質素作用後的已分化3T3-L1 和 HepG2 細胞中觀察到葡萄糖吸收的減少，相關實驗亦證實芝麻素和芝麻酚與 PPARγ 有直接交互作用，並可抑制其轉錄活性。值得注意的是，芝麻素和芝麻酚能夠降低分化3T3-L1 細胞中與有絲分裂原活化蛋白激酶 (MAPK) 信號途徑相關的成分的磷酸化。本研究深入探討芝麻素和芝麻酚抗肥胖效應的分子機制，發現芝麻素和芝麻酚透過 MAPK 信號途徑下調 PPARγ 及其下游基因的作用，其結果有助於未來相關研究並能夠應用在肥胖管理與治療上。
並列摘要
This study presents a comprehensive exploration of the anti-obesity effects of sesamin and sesamolin, two predominant lignans found in sesame seeds, known for their anti-inflammatory, anti-cancer, and neuroprotective properties, and their benefits in liver, cardiovascular diseases, and metabolic syndrome. Despite existing research, there has been a lack of thorough investigation into their specific mechanisms in combating obesity. This study therefore aimed to elucidate the regulatory effects of sesamin and sesamolin on adipogenesis, using 3T3-L1 cells as a model system. The central hypothesis was that sesamin and sesamolin inhibit adipogenic differentiation through the modulation of peroxisome proliferator-activated receptor γ (PPARγ). The research involved a detailed examination of the effects of these lignans on lipid accumulation, triglyceride formation, and the expression levels of key adipogenic transcription factors, including PPARγ and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, the impact of these lignans on downstream targets such as fatty acid binding protein 4 (FABP4), hormone-sensitive lipase (HSL), lipoprotein lipase (LPL), and glucose transporter 4 (GLUT4) were also investigated. A significant finding of this research was the dose-dependent reduction in adipogenic differentiation, triglyceride formation, and mRNA and protein expression levels of PPARγ and C/EBPα by sesamin and sesamolin. Furthermore, an attenuation of glucose uptake by these lignans in differentiated 3T3-L1 and HepG2 cells were observed, suggesting a direct interaction with PPARγ, inhibiting its transcriptional activity. Notably, sesamin and sesamolin were also found to decrease the phosphorylation levels of components within the mitogen-activated protein kinase (MAPK) signaling pathway in differentiated 3T3-L1 cells. This study contributes to the field by providing a deeper understanding of the molecular mechanisms underpinning the potential anti-obesity effects of sesamin and sesamolin. It highlights the role of these lignans in downregulating PPARγ and its downstream genes through the MAPK signaling pathway, offering valuable insights for future research and potential therapeutic applications in obesity management.