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| 題名: | 苦瓜籽油延緩體脂肪生成機制研究
Mechanistic studies on the anti-adiposity effect of bitter melon seed oil |
| 作者: | 張怡君 |
| 貢獻者: | 營養學系碩士班 |
| 關鍵詞: | c9, t11, t13-CLN;苦瓜籽油(BMSO);降體脂;PKA
Cis9, trans11, trans13-conjugated linolenic acid (c9, t11, t13-CLN);Bitter melon seed oil (BMSO);Anti-adiposity;PKA |
| 日期: | 2011-07-27 |
| 上傳時間: | 2011-10-17 16:52:05 (UTC+8) |
| 出版者: | 中國醫藥大學 |
| 摘要: | 苦瓜 ( Bitter melon；Momordica Charantia ) 在亞洲地區是一種日常食用蔬菜，也普遍用於降血糖。本實驗室先前已證實苦瓜全果凍乾粉有抗肥胖作用。另外在細胞實驗中，利用3T3-L1前脂肪細胞模式發現苦瓜籽中富含的特殊脂肪酸cis9, trans11, trans13-conjugated linolenic acid (c9, t11, t13-CLN)可抑制前脂肪細胞增生、分化並促進前脂肪細胞凋亡。為探討苦瓜的降體脂功能是否來自c9, t11, t13-CLN，我們選擇苦瓜籽油(Bitter melon seed oil; BMSO)為動物實驗材料，因它有高達50%的c9, t11, t13-CLN。先前給予不同劑量(5、10 及 15%) BMSO予小鼠 11週，證實BMSO比起大豆油更能有效抑制高脂飲食誘發肥胖，且呈現劑量反應關係。本研究擬在動物實驗進一步探討：(1) BMSO降體脂時間點、(2)BMSO降體脂作用機制、（3）BMSO對葡萄糖代謝安全性。
實驗一將C57BL/6J八週齡公小鼠分為兩組：大豆油組(30% soybean oil；HS)及苦瓜籽油組(15% soybean oil + 15% BMSO；HB)，分別飼養1、2、5、11 wk犧牲，結果發現攝取BMSO一週即見降體脂功效(包括皮下及內臟脂肪)，並持續至第5週，但意外的是11週功效減弱，此同時也發現飼料中c9, t11, t13-CLN降解，暗示了BMSO降體脂功效極可能來自於c9, t11, t13-CLN。分析第1、2與5週肝臟AMPK與PKA磷酸化蛋白，發現BMSO不影響肝臟AMPK活化，但第1與2週可見PKA活化增加；另外BMSO介入可見到脂肪組織出現crown-like structure (CLS)，伴隨脂肪組織TNF?捊W加及細胞凋亡，雖然也可能貢獻BMSO降體脂功效，但也引發長期補充BMSO對胰島素敏感性之關切。實驗二則將C57BL/6J小鼠分為對照組(22.5% soybean oil；HS)與實驗組(11.25% soybean oil + 11.25% BMSO；HB與HY)，HB與HY使用不同來源苦瓜品種(花蓮農改場提供)，飼養1、5與11 週犧牲。結果顯示，兩品系BMSO同樣補充一週即可見體脂降低，穩定持續至11週且功效相當。禁食血糖與胰島素顯示BMSO相較於大豆油至少不會惡化胰島素抗性。同時觀察到血清 TG與NEFA降低、肝臟TG也有降低趨勢。肝臟PKA活化再次於BMSO補充初期得證，伴隨肝臟fatty acid synthase (FAS) activity降低及acyl-CoA oxidase (ACO)活性增加，顯示肝臟lipogenesis下降及促進脂肪酸?珖韙?野i貢獻於BMSO降體脂。在脂肪組織發現BMSO介入使ACC磷酸化增加、perilipin蛋白質總量下降，推測BMSO也使脂肪組織lipogenesis下降並促進脂解。總合言之，BMSO確實可降體脂，其作用機制涉及活化PKA傳訊、改變肝臟與脂肪組織脂質代謝或促進生熱。
Bitter malon (Momordica charantia) is a vegetable commonly used in the asia countries, which is also well-known for its blood glucose-reducing effect. We have previously shown that the lyophilized bitter melon whole fruit is effective in anti-obesity. In an in vitro study using 3T3-L1 as an adipogenic model, cis9, trans11, trans13-conjugated linolenic acid (c9, t11, t13-CLN), a fatty acid presents at high levels in bitter melon seed oil, was found to inhibit proliferation and differentiation of preadipocytes and is apoptotic to preadipocytes. To test whether the bitter melon-mediated anti-adiposity effect is associated with c9, t11, t13-CLN, bitter melon seed oil (BMSO), which contains 50% c9, t11, t13-CLN, was used in animal feeding study. Two animal experiments were conducted in the present study aimed at investigating: (1) the time effect of BMSO associated anti-adiposity function, (2) the possible working mechanism, (3) the safety concerns of BMSO on glucose metabolism.
In Experiment I, C57BL/6J mice were divided into soybean oil group (30% soybean oil; HS group) and BMSO group (15% soybean oil + 15% BMSO; HB group). Mice were sacrificed after feeding experimental diets for 1, 2, 5 and 11 weeks. The body fat was significantly reduced in mice subjected to BMSO diet for 1, 2 and 5 weeks (vs. HS group). However, BMSO-mediated anti-adiposity effect was attenuated at 11 weeks. At this time point, we found c9, t11, t13-CLN was degraded in the BMSO diet. The unexpected accident suggested that BMSO–mediated anti-adiposity function might come from c9, t11, t13-CLN. At 1 and 2 weeks interventions, activation of cAMP-dependent protein kinase (PKA), but not AMPK, in liver was observed in HB group (vs. HS group). In addition, the presence of crown-like structure, accompanied with an increased TNF-?? production and cell apoptosis in adipose tissue were detected in HB group. This result provoked a deep concern regarding insulin sensitivity after a long-term BMSO intervention, even it display a prominent effect on anti-adiposity. In Experiment II, C57BL/6J mice were divided into three groups: control group (22.5% soybean oil, HS) and experiment groups (11.25% soybean oil + 11.25% BMSO; HB and HY). Two different strains of bitter melon seed (black and yellow coat) were used in HB and HY groups, respectively. Mice were sacrificed after feeding experimental diets for 1, 5 and 11 weeks. Results showed that BMSO significantly decreased adipose tissue weight from 1 week of intervention through the whole study period, regardless HB or HY was used. The fasting serum glucose and insulin levels showed the BMSO supplement conveyed no further deterioration on insulin sensitivity compared to HS group. The serum levels of TG and NEFA as well as the liver content of TG in BMSO groups tended to be lower than HS group. Again, BMSO groups showed a significant increase in PKA phosphorylation in liver at 1 week of intervention. A reduction in fatty acid synthase (FAS) and an increase in acyl-CoA oxidase (ACO) activities were observed in liver of BMSO supplementation groups, indicating a suppressed lipogenesis and an increased fatty acid β-oxidation might contribute to the anti-adiposity function of BMSO. In adipose tissue, we saw acetyl-CoA carboxylase (ACC) phosphorylation was increased, and total perilipin protein was decreased in BMSO groups, indicating a suppressed lipogenesis and enhanced lipolysis were also involved in BMSO’s effect. Overall, the working mechanism relevant to the anti-adiposity of BMSO could be attributed to an activation of PKA signaling pathway, which altered lipid metabolism in liver and adipose tissue, and promoted thermogenesis. |
| 顯示於類別: | [營養學系暨碩士班 ] 博碩士論文
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