山苦瓜改善高脂飲食誘發小鼠代謝異常、脂肪肝與肝相關基因 mRNA 表現

Wild bitter gourd ameliorates high-fat diet induced metabolic disorder, fatty liver and hepatic mRNA expressions of related genes in C57BL/6J mice.

10.6342/NTU201601776

董又慈

山苦瓜 ； 肝臟 ； 脂質代謝 ； 粒線體 ； 非酒精性脂肪肝 ； wild bitter gourd ； liver ； lipid metabolism ； mitochondria ； non-alcoholic fatty liver

臺灣大學生化科技學系學位論文

2016年

碩士

黃青真

繁體中文

隨著飲食及生活習慣的改變，近年來，全球肥胖與代謝異常盛行率急遽增加，肥胖者有較高風險罹患代謝症候群、非酒精性脂肪肝、第二型糖尿病等許多慢性疾病，因此如何有效控制已成為公共衛生之重要議題。過去研究指出，山苦瓜含有活化 PPARα 的活性分子， PPARα 主要參與肝臟脂質代謝調控：促進脂肪酸氧化、減少脂肪堆積、促進脂肪酸運輸等。此外，山苦瓜能透過多種機制進行血糖調節。近期本實驗室 in vivo 研究顯示餵食 5% 山苦瓜能藉由促進肝臟脂肪酸代謝、副睪脂褐化、促進肌肉與白色脂肪組織粒線體生合成及活性以增加能量消耗，有效改善高糖或高脂飲食造成的肥胖、胰島素抗性等症狀。 本研究先以高脂飲食誘導 C57BL/6J 公鼠產生肥胖後再給予 3% 或 5% 之花蓮四號山苦瓜全果凍乾粉 (BGP) 或其水解產物 (BGPa) ，探討肥胖後補充山苦瓜對血糖、血脂、肝臟脂質代謝與粒線體活性相關 mRNA 表現量等之影響，以及藉由內源性酵素水解前處理對山苦瓜功效之影響。結果顯示在高脂飲食誘發肥胖後添加山苦瓜於高脂飲食中能顯著改善高脂飲食造成的肥胖、高血糖、高膽固醇血症、非酒精性脂肪肝等代謝失調情形，無論有無經過水解處理，山苦瓜皆可以藉由活化肝臟 PPARα 促進脂肪酸氧化相關基因表現以改善肝臟脂質堆積情形。經水解後更可能藉由活化 LXRα 促進膽酸合成酵素基因表現，使其改善肝臟膽固醇堆積之效果提升。此外，水解後之山苦瓜改善高脂飲食對肝臟粒線體生合成、融合與分裂相關基因 mRNA 表現的降低情形顯著優於未處理之山苦瓜。 綜合以上，山苦瓜可以藉由促進肝臟脂肪酸分解及促進粒線體活性以舒緩高脂飲食造成的代謝壓力，以內源性酵素水解醣基後使山苦瓜減少肝臟膽固醇堆積及增加肝臟粒線體活性相關 mRNA 表現之效果提升，使其更能有效改善肥胖造成的非酒精性脂肪肝。

The prevalence of obesity and metabolic disorders over the world increases in recent decades, as a result of changes in the diet and life style. Obesity are linked to high risks of many chronic diseases, such as metabolic syndrome, non-alcoholic fatty liver disease, and type 2 diabetes, etc. It has thus become a key issue in public health. Previous studies demonstrated that wild bitter gourd extracts activate PPARα in a transactivation assay and active compounds have been identified. PPARα is known to regulate hepatic lipid metabolism by up-regulating genes of some metabolic pathway and leading to enhanced fatty acid oxidation, less fat accumulation, etc. In addition, wild bitter gourd can improve hyperglycemia through various mechanisms. Recent in vivo studies in our lab demonstrated that mice fed 5% wild bitter gourd powder (BGP) increased the energy expenditure by promoting hepatic fatty acid metabolism, browning of epididymal white adipose tissue and the function of mitochondria in skeletal muscle and white adipose tissue; thus, wild bitter gourd can ameliorate the obesity and the insulin resistance resulting from a high-sugar or high-fat diet. This study aims to examine effects of wild bitter gourd supplementation to high-fat diet induced obese mice on serum glucose and lipid, as well as the mRNA expressions of the hepatic lipid metabolism and hepatic mitochondrial function. Five groups of C57BL/6J male mice were fed an AIN-93G modified high-fat diet for 15 weeks and then followed by supplementing 0%, 3% BGP, 5% BGP, 3% hydrolyzed BGP (BGPa) or 5% BGPa in high-fat diet respectively. Our data suggests that the supplement of wild bitter gourd improve metabolic disorders induced by the high-fat diet, including obesity, hyperglycemia, hypercholesterolemia, and non-alcoholic fatty liver disease. BGP and BGPa can both decrease the hepatic lipid accumulation by increasing the mRNA expression levels of genes related to fatty acid oxidation through activating hepatic PPARα. Noticeably, only BGPa can up-regulate the mRNA expression level of the gene related to bile acid synthesis possibly by activating hepatic LXRα. These data suggested that BGPa might have additional benefit improving the hepatic cholesterol accumulation. In addition, the function of BGPa to ameliorate the down-regulated mRNA expression level of genes related to mitochondrial biogenesis, fusion and fission due to the high-fat diet is significantly better than BGP. In conclusion, wild bitter gourd may alleviate the metabolic disorder from the high-fat diet by facilitating the hepatic fatty acid catabolism and promoting mitochondrial activity. Also, wild bitter gourd hydrolyzed by its endogenous glucosidase enhances its ability to improve the hepatic cholesterol accumulation and increase the mRNA expression level of genes related to hepatic mitochondrial function. Based on this, BGPa ameliorates the obesity-induced non-alcoholic fatty liver more effectively than BGP.

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