2014-01-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/680563摘要：肥胖與許多代謝性疾病具有關聯性，其中包含糖尿病與心血管疾病等。子計劃3的目的為建立以西方飼糧誘發李宋豬產生代謝症侯群，並探討其於心律不整預後的重要性。本試驗以9月齡李宋豬為試驗模式，逢機分為2組，分別餵飼一般飼糧（C）或西方飼糧（W）為期5個月。結果顯示，W組之體重、全身脂肪分布率、血糖、三酸甘油酯與總膽固醇濃度皆顯著高於C組（P < 0.05）。W組於試驗末期也產生葡萄糖不耐之徵狀。試驗證實長期餵飼李宋豬西方飼糧，確實造成代謝症候群反應。在電生理試驗可觀察到W組的豬隻比C組有嚴重心室/心房顫動，後續相關分析仍在進行中。另外，在小鼠試驗中我們發現西方飼糧餵飼時間長短將引發心臟ER stress與autophagy的不同反應。ER stress比autophagy還要早被誘發以保護心臟功能以抵抗西方飼糧的壓力，但到16周後，autophagy與ER stress功能異常，無法保護心臟而造成細胞凋亡。長期餵飼西方飼糧引起小鼠心臟功能異常，提高adiponectin receptor 1表現則降低autophagy反應，改善心肌細胞的能量供應而減少細胞死亡。 綜觀上述，代謝症候群豬隻較健康豬容易引發心律不整，autophagy與adiponectin receptor 1調控代謝症候群心臟功能的運作，但是autophagy, adiponectin receptor 1與心律不整之間的關聯，則有待第三年的研究。<br> Abstract: Obesity is associated with many metabolic diseases, including diabetes and cardiovascular diseases. The objective of subproject 3 is to establish a Lee-Sung miniature pig model of Western diet-induced metabolic syndrome (MetS), and study the prognostic significance of MetS on arrhythmia. In our study, 9-month-old miniature pigs were randomly assigned to 2 groups for 5-month experimental periods: control diet (C) and Western diet (W). The results showed that W group had higher body weight and body fat ratio, elevated level of blood glucose, triglyceride and total cholesterol (P < 0.05) than C group. W pigs were glucose intolerant in the end of experiment, while C pigs were not. These results demonstrate that long-term feeding Western diet to Lee-Sung miniature pigs induced the metabolic syndromes. In addition, W pigs induced severer ventricular/atrial fibrillation than C pigs did, the related mechanisms are studied. In the mouse study, we found that Western diet-feeding period caused various responses of ER stress and autophagy. ER stress is an earlier event for caridoprotection than autophagy during the long-term Western diet stress. However, ER stress and autophagy lost the protection abilities and caused apoptosis after 16 wks- Western diet stimulation. Long-term Western diet feeding caused cardiac dysfunctions in the mouse model. However, upregulating the expression of adiponectin receptor 1 decreased the autophagic response, increased the energy supply, and therefore decreased cell death. To conclude, MetS pigs are more easily induced arrhythmia than the healthy pigs. Autophagy and adiponectin receptor 1 regulate the MetS heart function. However, the relationship among autophagy, adiponectin receptor 1 and arrhythmia need more studied in the third year.肥胖心室/心房顫動autophagy脂締素受體1obesityarrhythmiaautophagyadiponectin receptor 1