Coleus forskohlii萃取物及Garcinia indica萃取物於高脂飲食誘導肥胖的小鼠中具有減緩肥胖及調節腸道菌相的功效

Coleus forskohlii extract and Garcinia indica extract attenuated obesity and modulated gut microbiota in mice with high-fat diet

石苡昂(Yi-Ang Shih)

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(2018年)

https://doi.org/10.6342/NTU201802753

摘要

肥胖被認為是長期熱量的攝取和消耗間的不平衡所導致，且與第二型糖尿病、高血壓、冠狀動脈心臟病以及癌症等多種疾病高度相關，是全球引起死亡的第五大風險因素。因此，如何預防及延緩肥胖已為全球性健康議題。文獻指出，Coleus forskohlii中的Forskolin是一種腺苷酸環化酶 (adenylyl cyclase) 的促進劑，可促進脂肪細胞進行脂肪分解 (Lipolysis) 的速率而具有減緩肥胖之功效。另外， Garcinia indica萃取物中的Garcinol則在3T3-L1細胞實驗當中被發現到，可透過抑制脂肪細胞新生 (adipogenesis) 的方式而具有抗肥胖之潛力。近年來許多研究皆指出腸道菌群能夠影響宿主對於營養物質的吸收和能量分佈，因此腸道菌群在肥胖及代謝症候群等疾病的發病機制中扮演著重要的角色。因此，本研究採用Coleus forskohlii萃取物 (CFE)、Garcinia indica萃取物 (GIE) 及兩種萃取物之混合物，以3T3-L1細胞實驗及高脂飲食誘導小鼠肥胖的動物模式，探討單獨或是混合給予此兩種萃取物是否可以透過抑制脂肪細胞新生或是促進脂肪分解兩種不同路徑來達到抗肥胖之功效，亦或藉由腸道菌相之影響進而改善肥胖之狀況。細胞實驗結果顯示，CFE會促進3T3-L1脂肪細胞的脂解作用，GIE則會抑制3T3-L1前脂肪細胞的分化及減少油滴生成，而混合物組之結果與單獨CFE及GIE的組別相似。動物實驗結果顯示，CFE可藉由活化cAMP-dependent路徑促進C57BL/6小鼠之脂解作用，GIE則可抑制脂肪細胞新生相關轉錄因子PPARγ及C/EBPα之蛋白質表現量，且兩者皆具有促進脂肪酸β-氧化的效果，因此可達到抑制小鼠體重增加、減少白色脂肪組織重量的現象，此外CFE及GIE也具有降低血液中總膽固醇和三酸甘油酯及改善脂肪肝的效果，其中CFE組於此些方面的效果最好，而混合物組之效果則僅與GIE組相似，顯示CFE及GIE的組合對於抗肥胖功效並不具有協同作用。腸道菌相方面，CFE及GIE可減少腸道中Firmicutes/Bacteroidetes之比例，增加Ruminococcaceae科、Bacteroides屬及Lactobacillus reuteri等有益菌種之比例，並降低壞菌Desulfovibrio屬之比例。綜合上述結果，CFE對於減少脂肪堆積、降低血脂及改善脂肪肝具有較佳之效果，並能調節腸道菌相，因此具有抗肥胖之潛力。

關鍵字

肥胖 ； Coleus forskohlii ； Garcinia indica ； 脂肪分解 ； 脂肪細胞新生 ； β-氧化 ； 腸道菌相

並列摘要

Obesity is caused by an imbalance between long-term caloric intake and energy expenditure, and is highly correlated with various diseases such as type 2 diabetes, hypertension, coronary heart disease, and cancer, making it the fifth leading risk for global deaths. Therefore, how to prevent obesity has become a global health issue. Forskolin from Coleus forskohlii is a promoter of adenylate cyclase that promotes the breakdown of stored fats in fat cells, and may aid in weight loss. Garcinol is a polyprenylated benzophenone derivative obtained from Garcinia indica. Previous study has showed that garcinol can inhibit cell proliferation and adipogenesis in 3T3-L1 cells, and may have anti-obesity potential. In recent years, many studies have pointed out that the gut microbiota can affect the host's absorption of nutrients and energy distribution, so the gut microbiota may play an important role in the pathogenesis of obesity and metabolic syndrome. Therefore, in this study, we want to investigate the anti-obesity effects of Coleus forskohlii extract (CFE), Garcinia indica extract (GIE), and a mixture of these two extracts in 3T3-L1 cell model and high-fat diet (HFD)-induced obesity animal model. In addition, we would like to find out whether these two extracts can improve obesity through the influence of intestinal flora or not. The results showed that CFE promotes the lipolysis of 3T3-L1 adipocytes, while GIE decreased triacylglyceride content of 3T3-L1 adipocytes. The results of the mixture group were similar to those of CFE and GIE alone. In animal experiments, CFE promoted lipolysis in C57BL/6 mice by activating cAMP-dependent pathway, while GIE decreased protein level of adipogenesis-related transcription factors PPARγ and C/EBPα, and both of which promote fatty acid β-oxidation can therefore suppress the weight gain of mice and reduce the weight of white adipose tissue. In addition, CFE and GIE also have the effect of lowering total cholesterol and triacylglyceride levels in the blood and improving fatty liver. The CFE group is the most effective on these aspects, and the effects of mixture are similar to the GIE group, indicating that the combination of CFE and GIE does not have synergistic effect on anti-obesity. In terms of gut microbiota, CFE and GIE could decrease Firmicutes /Bacteroidetes ratio, increase beneficial bacteria such as Ruminococcaceae, Bacteroides and Lactobacillus reuteri, and decrease harmful Desulfovibrio compared with HFD-treated group. Based on the above results, CFE has a better effect on reducing fat accumulation, improving hyperlipidemia and fatty liver, and it can also regulate the gut microbiota. As a result, CFE has the potential to be developed as anti-obesity therapeutic agent.

並列關鍵字

Obesity ； Coleus forskohlii ； Garcinia indica ； Lipolysis ； Adipogenesis ； β-oxidation ； Gut microbiota

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