長期餵食山苦瓜對高脂飲食誘導肥胖小鼠代謝異常及白色脂肪組織褐化相關基因表現之效應

The Effects of Wild Bitter Gourd on High-Fat Diet Induced Metabolic Disorder and the Expression of Browning-Related Genes in White Adipose Tissue of C57BL/6J Mice

鄒尚瑀(Shang-Yu Zou)

指導教授 ： 黃青真

國立臺灣大學/生命科學院/生化科技學系/碩士(2016年)

https://doi.org/10.6342/NTU201602470

摘要

肥胖起因於長期能量攝取大於消耗，體內累積過多脂肪。而肥胖患者中，又以腹部肥胖者有較高機率罹患糖尿病、高血脂症及心血管疾病。代謝症候群指高血壓、高血糖、腹部肥胖與血脂異常等症狀至少三項存在者，未經適當控制則有極高風險轉為第二型糖尿病及心血管疾病。目前許多研究證實苦瓜具有抗肥胖及改善代謝異常之潛力。本實驗室發現餵食C57BL/6J小鼠山苦瓜全果凍乾粉之高糖飲食25週後，能促進白色脂肪褐化相關基因表現。目前研究認為，白色脂肪褐化可增加個體熱量消耗，對抗肥胖。苦瓜具有多項生理活性，其中所含之三萜類化合物具有血糖調節能力，並以不帶醣基之形式調節效果較佳。過去於3T3-L1脂肪細胞模式中，發現山苦瓜酸水解產物之正己烷萃物能改變促褐化效果。本論文旨在探討山苦瓜及其水解產物，改善高脂飲食誘發肥胖小鼠之代謝異常及促進脂肪褐化之效果。
本實驗以高脂飲食誘發C57BL/6J小鼠肥胖15週，再分5組分別餵食高脂飼料 (HF組)、高脂飼料添加3%山苦瓜粉 (3%BGP組)、高脂飼料添加3%水解山苦瓜粉 (3%BGPa組)、高脂飼料添加5%山苦瓜粉 (5%BGP組) 及高脂飼料添加5%水解山苦瓜粉 (5%BGPa組) 餵食20週，另以飼養期間全程餵食chow diet之C組作為正常對照組。結果顯示，短期 (11週) 攝入3%水解山苦瓜及5%山苦瓜及其水解產物可有效降低血糖; 長期 (20週) 攝入則有降低體重增加之效果。短期及長期攝入3%及5%山苦瓜及其水解產物皆可有效降低血清中總膽固醇。進一步分析 脂肪基因表現，5%山苦瓜可促進棕色脂肪組織 (BAT) 中產熱功能及粒線體生合成基因表現，並增加腎周圍脂肪 (RWAT) 中生熱及粒線體生合成基因表現。5%水解山苦瓜則可促進副睪脂肪組織 (EWAT) 褐化指標及粒線體生合成基因表現。綜合以上，山苦瓜及其水解產物能促進棕色脂肪產熱功能及白色脂肪褐化基因之表現，並降低血清總膽固醇及增加胰島素敏感度，改善小鼠肥胖及代謝異常情形。

關鍵字

肥胖 ； 山苦瓜 ； 褐化 ； 粒線體 ； 三萜類化合物 ； 水解

並列摘要

Obesity is defined as abnormal or excessive body fat accumulation due to excessive energy intake and less energy expenditure. Abdominal obesity is a risk factor for metabolic disorder related to diabetes, hyperlipidemia and cardiovascular diseases. Metabolic syndrome is the clustering of various risk factors those predictive higher risks of type 2 diabetes and cardiovascular diseases. Numerous studies have demonstrated that bitter melon (Momordica charantisa) has potential for ameliorating obesity and metabolic syndrome. Previous studies showed that mice fed high sucrose diet supplemented with bitter gourd powder (BGP) for 25 weeks had higher mRNA expression of genes related to browning in white adipose tissue, which is considered an effective way to increase energy expenditure and combat obesity. Bitter melon is known to have a number of health benefits. For instance, the triterpenoids in bitter melon, especially aglycone forms, have been shown to activate AMPK and increase glucose uptake in adipocytes and myocytes. It has been demonstrated the hexane extracts of acid-hydrolyzed BGP has been shown to induce “browning” related mRNA expressions in the 3T3-L1-cell model. In this study, we aimed to examine the effects of BGP and its hydrolysis product on ameliorating metabolic disorders and stimulating adipose tissue browning of high fat diet induced obese mice.
C57BL/6J mice were fed the high fat diet for 15 weeks and then assigned into 5 groups, including: HF group (fed the high fat diet), 3%BGP group (fed the high fat diet supplemented with 3%BGP), 3%BGPa group (fed the high fat diet supplemented with 3% hydrolyzed BGP), 5%BGP group (fed the high fat diet supplemented with 5%BGP), and 5%BGPa group (fed the high fat diet supplemented with 5% hydrolyzed BGP). They were fed the respective test diets for 20 week. Another group of mice fed a chow diet throughout the 35 weeks periods served as the normal control.
Compared to the HF group, mice in the 3%BGPa, 5%BGP and 5%BGPa groups had significantly lower serum glucose at 11 weeks, and significantly lower body weight gain after 20 weeks. Serum cholesterol level of 3%BGP, 3%BGPa, 5%BGP and 5%BGPa groups were significantly lower than those of the HF group at 11 and 20 week. The mRNA expressions of thermogenic and mitochondrial biogenic genes in BAT and RWAT of the 5%BGP were significantly higher than the HF group. In addition, mice fed the 5%BGPa diet showed significantly higher mRNA expression of beige markers and mitochondrial biogenic genes in EWAT.
In conclusion, BGP and hydrolyzed BGP up-regulated the expression of thermogenic genes in BAT and brown-related genes in visceral white adipose tissue, reduced serum cholesterol and increased insulin sensitivity. Results of this study support the effects of BGP and its hydrolysis product on ameliorating the diet-induced obesity and metabolic disorder, and presumably can promote browning in mice.

並列關鍵字

obesity ； bitter melon ； browning ； mitochondria ； triterpenoids ； hydrolysis

參考文獻

謝婉郁 (2005)。山苦瓜改善血糖血脂代謝異常之效應探討。國立臺灣大學微生物與生化學研究所。

黃婷妮 (2010)。山苦瓜萃物暨其區分物之腸泌素效應。國立臺灣大學生命科學院生化科技學系。

蔣汶龍 (2014)。探討山苦瓜對飲食誘導肥胖模式小鼠骨骼肌粒線體增殖之影響。國立臺灣大學生命科學院生化科技學系。

林德岳 (2013)。山苦瓜萃取暨其酵素水解最佳化與三萜類成分之探討。國立臺灣大學生命科學院生化科技學系。

王柏凱 (2015)。山苦瓜酸水解萃物影響3T3-L1前脂肪細胞褐化相關基因mRNA的表現量。國立臺灣大學生命科學院生化科技學系。