2010-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/670393摘要：根據2008年國民營養調查顯示，台灣地區49.7%的男性與34.7%的女性有過重或肥胖的問題。此外，因肥胖而引起的相關代謝疾病更造成每年高達兩百一十六億台幣醫療支出的耗損。因此，若能了解肥胖引發的代謝疾病致病機轉，不僅能維護國人健康，更有助於減少國家的醫療支出。 肥胖相關的代謝疾病之中，以心血管疾病最引起關注。除因心血管疾病高居國人十大死因第二位之外，肥胖患者常好發的心肌肥大，又是心臟衰竭的主要症狀。若能釐清肥胖與心肌肥大的關連，將可間接降低心血管疾病死亡的比例。脂締素具有保護心臟的功效，但肥胖者血液中脂締素濃度偏低。故本計劃以adipoR1轉基因小鼠為模型，藉由增加脂締素受體1的表現，強化脂締素對心肌細胞的影響，藉此探討脂締素在心肌肥大所扮演的角色。 計劃目的： 1. 建立飲食引起肥胖的小鼠模型 2. 釐清正常心肌細胞與肥大心肌細胞的分子機制 3. 研究脂締素及其受體抑制心肌細胞肥大之可能機制 4. 產製大量表現adipoR1基因的心肌細胞 5. 尋找可能參與之蛋白質及其生物活性探索 6. 尋找可以提高心肌細胞內adipoR1表現的不飽和脂肪酸種類 本研究結果將可釐清脂締素在改善心肌肥大的作用機制，進一步提供心衰治療的可能新方向。 <br> Abstract: According to National Nutrition Survey 2008, 49.7% of male and 34.7% of female are overweight or obese in Taiwan. Furthermore, annual medical costs of obesity-induced metabolic diseases accounts for NT 21.6 billions of the national healthcare expenditure. As a result, to find out the pathogenesis of obesity-induced metabolic disease not only promotes the public health but also reduce the national medical expenditure. Cardiovascular disease is the most concerning issue among all the obesity-induced diseases due to its second place of the leading causes of death in Taiwan. In addition, myocardial hypertrophy, often observed in the obese subjects, is the major symptom of heart failure. To clarify the relationship between obesity and myocardial hypertrophy might indirectly decrease the death caused by cardiovascular diseases. Adiponectin is reported as cardioprotective. However, obese patients have a lower plasma adiponectin than the healthy subjects do, suggesting less protection in the hearts of obese patients. Therefore, the adipoR1 transgenic mice model will be used in this project, over-expression of adipoR1 to amplify the effect of adiponectin on cardiomyocytes will be applied to study the role of adiponectin on myocardial hypertrophy. The major goal for this project is: 1. To establish the mouse model of diet-induced obesity 2. To elucidate the differences of molecular regulation between healthy and hypertrophic cardiomyocytes 3. To study the effect of adiponectin and adipoR1 on the inhibition of myocardial hypertrophy 4. To overexpress adipoR1 gene in cardiomyocytes 5. To explore the novel proteins and study their bioactivity on cardiomyocytes 6. To explore the possible unsaturated fatty acids with the ability to increase the adipoR1 expression in the cardiomyocytes The results of this project will elucidate the protective mechanism of adiponectin and adipoR1 against myocardial hypertrophy, and may provide the potential therapeutic choice for heart failure.脂締素脂締素受體1肥胖心肌肥大能量代謝抗氧化能力adiponectinadipoR1obesitymyocardial hypertrophyenergy metabolismantioxidant capacity