| 摘要: | 肥胖可增加??病、心血管疾病、高血壓、膽囊疾病及癌症等疾病發病?，因此預防肥胖，已成為重要身體保健議題。脂肪細胞?目增加，指由前脂肪細胞分化成為成熟脂肪細胞之過程，稱為脂肪細胞生合(adipogenesis)，過?增加adipogenesis，在肥胖及肥胖相關疾病病因上扮演重要角色。前脂肪細胞分化為成熟脂肪細胞過程中，細胞形態由前脂肪細胞之紡錘型轉變為脂肪細胞的圓球型。此外，相較於前脂肪細胞，成熟脂肪細胞增加脂質新生作用及胰島素敏感?，並增加表現脂肪細胞特定蛋白質，包括：與脂肪細胞分化相關轉?因子peroxisome proliferator-activated receptor γ (PPARγ)、 CCAAT/enhancer binding proteins (C/EBPs) α和β、及adipose differentiation and determination factor 1/sterol regulatory element binding protein-1c (ADD1/SREBP1c)，與脂肪代謝相關酵素及蛋白質glycerol-3-phosphate dehydrogenase (GPDH)、fatty acid synthase (FASN)、acetyl-CoA carboxylase (ACC) 、aP2、perilipin。現今已知肥胖與慢性發炎反應有關，肥胖會增加吞噬細胞侵入脂肪組織?目，而吞噬細胞分?物質 (macrophage-secreted factors)增加脂肪細胞分?TNF-α、IL-6、和 resistin等促發炎adipokines、?低adiponectin和PPARγ表現，及增加NF-κB活化。此外，脂肪細胞發炎亦會減少脂肪細胞Glut 4 及insulin receptor substrate-1表現?，抑制Akt磷酸化，?低胰島素誘發脂肪細胞Glut 4轉移至細胞膜、減少脂肪細胞glucose uptake及抑制脂肪水解作用能?等胰島素阻抗現象。研究發現，肥胖引起的脂肪細胞發炎與第2型??病、心血管疾病及代謝症候群等與肥胖有關的病症發生有密?關係。香菜 (Coriandrum sativum L.) 又名芫荽、胡荽，台灣各地均有栽培。本實驗室研先前究結果證實95%酒?之香菜莖及?萃出物可經由抑制Lipopolysaccharide (LPS)誘發轉?因子NF-κB 活化及MPAKs 磷酸化之作用，抑制LPS 誘發吞噬細胞RAW264.7 發炎反應。由液相層析質譜儀分析證實95%酒?之香菜莖及?萃出物富含rutin。為??解香菜酒?萃出物保健功效，本研究計畫目的在評估香菜酒?萃出物對調控adipogenesis 及RAW264.7 macrophage conditional medium 誘發脂肪細胞發炎反應及胰島素阻抗之影響及對減少高脂飲食誘發小鼠肥胖之功效。此研究計劃實驗結果有助於?解香菜酒?萃出物對抗肥胖及預防第二型??病、心血管疾病及代謝症候群等與肥胖有關的病症發生之功效。此外，由本實驗室研究先前結果可知rutin 為香菜酒?萃出物中含?最多的天然植物化合物，故本研究計畫加入rutin 處?組，以評估rutin 是否為香菜酒?萃出物具保健功效之重要天然植物化合物。
Obestiy is a major public health problem and is a significant risk factor for many serious illnesses such as heart disease, type 2 diabetes hypertension, gallbladder disease and cancer. Adipognesis is the process by which mature fat cells are formed from preadipocytes. During adipocyte differentiation, cell concert from a fibroblastic to a spherical shape. Compared with preadipocyte, the ability of de nova lipogenesis and insulin sensitivity were increased in mature adipocytes. The mature adipocytes increase the expression of transcription factors such as peroxisome proliferator-activated receptorγ (PPARγ), CCAAT/enhancer binding proteins α and β, adipose differentiation and determination factor 1/sterol regulatory element binding protein-1c and the enzymes and proteins related to lipid metabolism such as glycerol-3-phosphate dehydrogenase, fatty acid synthase, acetyl-CoA carboxylase , aP2, and perilipin. Obesity is a chronic inflammatory response and obesity with enlarged fat cells is associated with an increased number of macrophages in the adipose tissue surrounding individual adipocytes. The macrophage-secreted factors released from macrophage could induced increased release proinflammatory mediators such as TNF-α, IL-6 and resistin and decreased the expression of adiponectin and PPARγ and increase the activation of NF-κB. Additionally, adipocyte inflammation decreased the expression of Glut 4 and IRS-1 and the Akt phosphorylation and decrease the insulin induced Glut 4 translocation and glucose uptake by adipocyte which is related to insulin resistance. Data from our lab have showed that the both leaf and stem of Coriandrum sativum ethanolic extract (CSEE) decreased lipopolysaccharide (LPS)-induced NO and prostaglandin E2 production, as well as inducible nitric oxide synthase, cyclooxygenase-2 and pro-interleukin-1β expression. Moreover, our data demonstrated that the inhibitory activity of Coriandrum sativum on LPS-induced inflammatory responses, at least in part, is caused by Coriandrum sativum modulating the NF-κB activation and mitogen-activated protein kinase pathway. Liquid chromatography/Mass spectrometry analysis in this report showed that rutin concentrations in stem and leaf of CSEE were 130.5 and 42.0 μg/g, respectively. In order to know the health benefits of SCEE, the objective of this study proposal is to explore the role of CSEE on modulating adipogenesis and RAW264.7 macrophage conditional medium induced adipocyte inflammation and insulin resistance. The result of this proposal could elute the role of CSEE on prevention of obesity, type 2 diabetes, heart disease and metabolic syndrome. |
