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標題: | 影響3T3-L1細胞株分泌細胞激素之食材對高油飲食小鼠的免疫調節作用 Effects of dietary factors on cytokines profile of 3T3-L1 cell and their in vivo effects on immune regulatory in mice fed high-fat diet |
作者: | Zhi-Xiong Kang 康智雄 |
指導教授: | 林璧鳳(Bi-Fong Lin) |
關鍵字: | 胰島素抗性,發炎反應,M2 巨噬細胞,Th1免疫反應, insulin resistance,inflammation,M2 macrophage,Th1 immune response, |
出版年 : | 2009 |
學位: | 碩士 |
摘要: | 肥胖者體內處於低程度發炎現象而導致了胰島素抗性,脂肪組織內的巨噬細胞型態也影響著胰島素敏感性,有研究指出脂肪細胞所分泌的IL-4會促進M2巨噬細胞生成而具有抗發炎增加胰島素敏感性的功效。本研究首先以3T3-L1脂肪細胞株,篩選具促進IL-4分泌量及降低lipopolysaccharide (LPS) 刺激下 IL-6與MCP-1促發炎細胞激素分泌量之抗胰島素抗性潛力食材樣品。篩選結果顯示,苦瓜(bitter gourd powder, BGP)、靈芝免疫調節蛋白(Ganoderma microsporum immunomodulatory protein, GMI)及食品級靈芝免疫調節蛋白 (f-GMI)均可顯著促進IL-4分泌且抑制成熟脂肪細胞IL-6與MCP-1。
正常飲食 (AIN-76) 情況下,給予C57BL/6J小鼠餵食GMI後具有降低血糖的效果。但在高油飲食誘發肥胖的動物模式下,餵食BGP、GMI與f-GMI,5週後發現f-GMI與BGP都具有降低空腹血糖的功效,而BGP更具有降低HOMA-IR index的能力。 In vivo,體重與脂肪組織IL-4基因表現量達顯著負相關 (r = -0.46, p=0.0001) ,血糖與脂肪組織IL-4基因表現量兩項指標也有顯著負相關 (r = -0.31, p=0.01),顯示體重及血糖增加會降低脂肪組織IL-4的表現量;體重與脾臟分泌IL-4含量也呈顯著負相關 (r = -0.28, p =0.01),顯示肥胖者體內較傾向Th1免疫反應。在脂肪組織,BGP與f-GMI均可顯著促進IL-4表現及M2 巨噬細胞生成,肝臟中M2 巨噬細胞生成的現象也顯著較HF組高。在高油飲食誘發胖小鼠肥胖模式下,餵食BGP與f-GMI的小鼠脾臟細胞在Con A刺激下,IFN-gamma 及IL-2分泌量顯著下降,顯示此兩食材樣品均有助於改善肥胖小鼠體內傾向Th1免疫反應的情形。綜合以上實驗結果得知,BGP及f-GMI可能藉由提高IL-4表現量,促進脂肪組織及肝臟M2 巨噬細胞生成;以及降低Th1細胞激素IFN-gamma及IL-2而具有改善肥胖發炎及胰島素抗性的現象。 Obesity is associated with low-grade system inflammation that results in insulin resistance. Adipose tissue macrophage (ATM) phenotype switch could affect insulin sensitivity. Adipocyte-derived IL-4 could promote M2 macrophage phenotype switch as well as ameliorate insulin resistance. First, using 3T3-L1 cell culture, potential dietary components which could increase IL-4 secretion as well as inhibit LPS-stimulated pro-inflammatory cytokines, IL-6 and MCP-1, were identified. The results showed BGP (Bitter gourd poeder, BGP), GMI(Ganoderma Modulatory Immunoglobulin, GMI) and f-GMI (Food Ganoderma Modulatory Immunoglobulin, f-GMI) could inhibit pro-inflammation cytokines secretion and increase IL-4 secretion. These dietary components were subsequently tested to verify their ability to ameliorate insulin resistance. In vivo, GMI improved blood sugar of C57BL/6J mice that were fed the AIN-76 diet with 50% sucrose. Improvement of fasting blood sugar could be observed in C57BL/6J mice that were fed a 30% fat diet supplemented with BGP or f-GMI for 5 weeks. BGP also decreased HOMA-IR index. BGP increased IL-4 mRNA expression in adipose tissue as well as M2 phenotype switch in adipose tissue and liver. f-GMI increased M2 phenotype switch in adipose tissue. In liver, f-GMI increased M2 phenotype switch and IL-4 mRNA expression. BGP and f-GMI significantly lowered IFN-gamma and IL-2 secretion from Con A-stimulated splenocytes. Furthermore, negative correlations were observed between body weight and IL-4 mRNA expression in adipose tissue (r = -0.46, p =<0.0001), and between blood sugar and IL-4 mRNA expression in adipose tissue (r = -0.31, p =0.01). The results show high body weight and blood sugar could inhibit IL-4 mRNA expression in adipose tissue. There was also a negative correlation between body weight and IL-4 secretion from splenocyte (r = -0.28, p =0.01), which suggests that obesity is prone to Th1 immune response. In conclusion, BGP and f-GMI increase M2 phenotype switch in adipose tissue and liver through IL-4 secretion. BGP and f-GMI could reduce IFN-gamma and IL-2 secretion from Con A-stimulated splenocytes. The aforementioned dietary components ameliorate insulin resistance through their inhibition of Th1 immune response abilities. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43596 |
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