不同化學組成含量之多甲氧基類黃酮抑制脂肪細胞 新生及減緩高脂飲食誘導小鼠之肥胖

Different chemical compositions of polymethoxyflavones (PMFs) inhibit adipogenesis in 3T3-L1 preadipocytes and suppress obesity in high-fat diet-feeding C57BL/6 mice

張瑋恬(Wei-Tien Chang)

指導教授 ： 潘敏雄

國立臺灣大學/生物資源暨農學院/食品科技研究所/碩士(2019年)

https://doi.org/10.6342/NTU201904161

摘要

隨著社會經濟環境急速變遷與飲食習慣的改變，造成肥胖情形與日俱增 。肥胖將導致罹患許多代謝機能異常疾病的發生，世界衛生組織已將肥胖列為一種慢性疾病且衍生出 〝Globesity〞 (全球肥胖) 一詞，由此可見如何預防肥胖為全世界健康重要課題之一。多甲氧基類黃酮 (Polymethoxyflavones, PMFs) 存在於柑橘類的果皮中，研究發現其具有廣泛的生物活性，如抗發炎、抗癌、抗氧化等功效，目前PMFs抑制脂肪細胞分化的機制尚未清楚，因此本研究以細胞及動物模式探討PMFs抑制脂肪形成的功效和分子機制。細胞實驗加入誘導劑，誘導3T3-L1前脂肪細胞分化，並處理不同含量的PMFs分析其抑制脂肪細胞分化的活性。Oil Red O染色結果顯示PMFs可抑制脂肪細胞油滴的形成。在動物實驗方面，餵食不同含量濃度PMFs-A、B、C可以減少高油脂飲食誘導肥胖小鼠體重以及性腺、腹部脂肪重量的增加，性腺脂肪切片顯示其脂肪細胞大小也有顯著性的縮小，而肝臟切片結果亦可看出脂肪空泡的數量和大小減少；整體又以PMFs-C的效果最為顯著，其次為PMFs-A及PMFs-B。西方墨點法結果顯示PMFs可以透過增加pAMPK的表現量降低脂肪細胞分化轉錄因子C/EBPα和PPARγ減少脂肪酸的形成，進而減少三酸甘油脂的合成。綜合上述結果顯示，PMFs具有抑制脂肪新生作用之功效，並改善高脂飲食誘導之肥胖，能減緩體脂肪生成及脂肪肝的發生，具有開發成不易形成體脂肪的保健食品之潛力，且有趣的是雖然在減少體重上以PMFs-C最為顯著，但在體脂肪率結果顯示不同含量的PMFs皆有顯著減少體脂肪生成之功效。此一發現未來是否可以與現今健康議題；老年人的肌少症做連結，藉由補充不同含量之PMFs達到增加肌肉量、提升代謝能力進而減少體脂肪生成有待更多研究來評估證實。

關鍵字

肥胖 ； 脂肪細胞新生作用 ； 多甲氧基類黃酮 (PMFs) ； 高脂飲食

並列摘要

Obesity problems are associate with the rapid changing social and economic environment. Obesity leads to the occurrence of metabolic syndromes. World Health Organization identifies emphasize the important obesity as a chronic disease and the term, ‘Globesity’ the compound word, made of global and obesity , was created. Polymethoxyflavones (PMFs) are found in citrus peel. Some research have suggested that PMFs have anti-inflammatory, anti-cancer, anti-oxidation and other biological activities. However, the inhibitory mechanisms of adipocyte differentiation by PMFs are still unclear. Therefore, this study used in vitro and in vivo models to explore PMFs’ inhibitory effects on the formation of lipid in adipocytes. In the in vitro study, 3T3-L1 preadipocytes were induced inducer mix (DMI) and treated with different compositions of PMFs to evaluate its inhibitory effects on adipocytes differentiation. Results of Oil Red O staining showed that PMFs can inhibit the formation of oil droplets in fat cells. Results of the in vivo study showed that feeding high-fat diet-induced obese mice with different compositions of PMFs-A, B, C reduced their body weight gain, perigonadal fat weight and retroperitoneal fat weight. Gonadal fat biopsy showed a significant decrease in fat cell size, furthermore, histological staining of liver sections showed reduced numbers and sizes of fat vacuoles.；The effect of PMFs-C was the most significant, and PMFs-B effect was greater than PMFs-A. Results of western blot showed that PMFs lowered the fat cell differentiation transcription factor C / EBPα and PPARγ, while increased the amount of pAMPKα, which in turn reduced the synthesis of triglycerides. Based on these results, that PMFs may inhibit hypertrophy in adipocyte, improved high-fat diet-induced obesity and retarded body fat formation and occurrence of fatty liver. Our results showed that PMFs had the potential to be developed into a functional health food that could alleviate the formation of body and liver fats. Interestingly, although PMFs-C were the most significant on weight loss, different compositions of PMFs on body fat ratio results showed significant reductions in body fat production. Whether this finding can be linked to today's health issues or to the myasthenia of the elderly, and by supplementing different compositions of PMFs to increase muscle mass and increase metabolic capacity to reduce body fat production is yet to be confirmed.

並列關鍵字

Obesity ； Adipogenesis ； Polymethoxyflavones (PMFs) ； High-fat diet

參考文獻

Aguirre, L., Fernandez-Quintela, A., Arias, N., & Portillo, M. P. (2014). Resveratrol: anti-obesity mechanisms of action. Molecules, 19(11), 18632-18655.

Bays, H. E., Gonzalez-Campoy, J. M., Bray, G. A., Kitabchi, A. E., Bergman, D. A., Schorr, A. B., Henry, R. R. (2008). Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther, 6(3), 343-368.

Berg, A. H., Combs, T. P., & Scherer, P. E. (2002). ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab, 13(2), 84-89.

Bradford, P. G. (2013). Curcumin and obesity. Biofactors, 39(1), 78-87.

Choi, S. Y., Hwang, J. H., Ko, H. C., Park, J. G., & Kim, S. J. (2007). Nobiletin from citrus fruit peel inhibits the DNA-binding activity of NF-kappaB and ROS production in LPS-activated RAW 264.7 cells. J Ethnopharmacol, 113(1), 149-155.