| 摘要: | 在亞洲，苦瓜（Bitter melon; Momordica charantia）為廣泛使用的食材。已有研究指出，苦瓜具降血糖、降血脂和抗發炎的作用，但其作用機制與功能性成分仍不明確。近來，有研究顯示苦瓜可活化Peroxisome proliferator - activated receptor (PPAR)α和γ，暗示苦瓜在預防和治療代謝症候群上具有應用之潛力。目前臨床廣泛使用之Thiazolidinedione (TZD)治療糖尿病藥物雖可改善胰島素敏感性，但卻具有肥胖的副作用。因此，本研究擬利用體內模式探討山苦瓜對於改善大鼠腹部體脂堆積和胰島素敏感性之功效並與TZD藥物做比較。
實驗採用40隻6週齡雄性Wistar大鼠，其中34隻先以含30%奶油的高脂飲食餵食3週誘導肥胖後，分成4組。BM組(含5%山苦瓜凍乾粉之高脂飲食)、EAE組(含0.25%山苦瓜凍乾粉乙酸乙酯萃物之高脂飲食)、HF組(高脂對照)及TZD組(含0.01% Pioglitazone之高脂飲食做為正對照)。另外6隻大鼠餵食含5%新鮮大豆油（LF組）做低脂對照。分組餵食9週後犧牲，分別取腹膜後脂肪、副睪脂肪和腹股溝脂肪秤重代表腹部脂肪堆積。取腹膜後脂肪和副睪脂肪進一步分析脂肪細胞大小、三酸甘油酯和DNA含量、脂質生合成酵素活性和脂解速率與脂肪細胞分化相關基因表現。在實驗期間，每隔3週採取尾巴血測量禁食血糖及胰島素。
結果顯示，TZD組在體重上顯著高於LF組(p < 0.05)，此結果與TZD藥物肥胖的副作用相符合。在腹部脂肪重量方面，HF組、EAE組和TZD組都顯著高於LF組(p < 0.006)，而BM組與LF組無顯著差異，表示山苦瓜凍乾粉可以改善高脂飲食誘導的腹部體脂堆積。分離自腹膜後脂肪和副睪脂肪的脂肪細胞，其大小比例分佈的結果顯示，BM組與HF組相較之下，有較多小的以及較少大的脂肪細胞。此外，BM組脂肪組織三酸甘油酯堆積有減少的傾向。Glycerol – 3 - phosphate dehydrogenase (G3PDH)是脂肪細胞中重要的脂質合成酵素。BM組與LF組副睪脂肪中G3PDH活性，皆顯著低於TZD組(p < 0.05)。在北方點墨定量結果中，BM組副睪脂肪的ADD1 / SREBP1c調控脂肪酸生合成之轉錄因子mRNA顯著低於TZD組(p < 0.05)。HF組在高脂飲食下會誘發高胰島素血症，但此現象不發生在TZD組和BM組。
以上這些結果指出山苦瓜如同TZD藥物可改善高脂飲食誘發之高胰島素血症，但相較於TZD有肥胖的副作用，山苦瓜反而抑制腹部體脂堆積。並且山苦瓜的降體脂作用可能與抑制脂質生合成有關。然而，本研究中使用的山苦瓜凍乾粉乙酸乙酯萃物也許劑量不足，並沒有呈現如山苦瓜凍乾粉之效用。
In Asia countries, bitter melon (Momordica charantia; BM) is a commonly used vegetable. It had been reported that the bitter melon has hypoglycemic, hypolipidemia and anti - inflammatory effects. But its mechanism and functional component are still unknown. Recently, bitter melon was found to activate both peroxisome proliferator - activated receptor (PPAR) α and γ which may be valuable in prevention and amelioration of metabolic syndrome. The clinically used antidiabetic drug TZD (thiazolidinedione) is effective in ameliorating insulin resistance, but has side effect of obesity.
In this study, the effect of wild BM lyophilized powder on anti - adiposity and insulin sensitivity in high fat diet fed rats was evaluated and compared with the antidiabetic drug TZD. We used forty Wistar male rats at the age of 6 weeks. Thirty-four rats were fed with high fat high sugar diet containing 30% butter to induce obesity, then divided into four groups: BM (a high fat diet containing 5% wild BM lyophilized powder), EAE (a high fat diet containing 0.25% EA extract from wild BM lyophilized powder), HF (a high fat diet serve as a high fat control), and TZD (a high fat diet containing 0.01% clinically used antidiabetic drug - pioglitazone, serve as a positive control). For comparison, six rats fed with a low fat diet containing 5% soybean oil serve as LF group. After 9 weeks, rats were sacrificed and abdominal fat including retroperitoneal, epididymal, and injuinal fat were excised and weighted. Epididymal and retroperitoneal fat were also used for determination of adipocyte size, triglycerides and DNA contents. The activities of enzymes participate in lipogenesis and lipolysis, and the genes expression of adipocyte differentiation markers were also determined in epididymal and retroperitoneal fat pads. At wk 0, 3, 6, 9, fasting blood was collected from tail for glucose and insulin determination.
Our results showed, the body weight gain of TZD group of rats was significantly higher than that of LF group of rats (p < 0.05), and this was in accordance with the well - known TZD side effect of obesity. HF, EAE and TZD group of rats also showed a significantly (p < 0.006) higher abdominal fat accumulation (retroperitoneal, epididymal and injuinal fat) than LF group, but there was no significant difference between BM and LF groups of rats. This result indicated that wild BM lyophilized powder was effective in inhibiting abdominal fat accumulation induced by high fat diet. The distribution of adipocytes size, isolated from retroperitoneal and epididymal fat, showed there were more smaller cells and less larger cells in BM group of rats when compared with those of HF group of rats. In addition, the triglycerides contents in adipose tissue of BM group of rats tended to be lowered. In epididymal fat, the activity of glycerol – 3 - phosphate dehydrogenase (G3PDH) which is an important lipogenic enzyme in adipose tissue, was comparable between BM and LF, and significantly lower than TZD group of rats (p < 0.05).
Northern blot showed that ADD1 / SREBP1c mRNA, a transcription factor for regulating fatty acid synthesis, was significantly lower in BM group of rats than TZD group of rats (p < 0.05) in epididymal fat. Hyperinsulinemia induced by high fat diet was only observed in HF , but not in TZD and BM group of rats.
These results indicate wild bitter melon, as well as TZD, could ameliorate insulin resistance induced by high fat diet. In contrast to the well - known obesity side effect of TZD, wild bitter melon is more beneficial in inhibiting abdominal fat accumulation. The anti - adiposity effect of wild bitter melon may be related to the inhibition of lipogenesis. However, the dose of EA extract from wild BM lyophilized powder used in this study (0.25%) may be too low to show its effect. |
