2009-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/652660摘要：過氧化小體增生活化受體γ與δ及其配體在脂肪細胞分化之功能 過氧化小體增生活化受體γ（PPARγ）可促進脂肪細胞分化，亦為參與調節脂質代謝之重要轉錄因子，而PPARδ亦為調節脂質代謝之轉錄因子。過去的研究中，對於此兩種過氧化小體增生活化受體之交互作用尚未釐清。本研究室已證明應用體外培養小鼠之肌纖維母細胞，分別轉染豬之正常型PPARγ與經突變型PPARγ，透過配體的活化可誘發肌纖維母細胞分化為脂肪細胞，其中又以突變型PPARγ轉分化之能力最強。此外，PPARδ促進脂質分解的研究只在許多鼠類中被證明，對於豬隻相關基因功能之研究則付之闕如。所以本計畫擬研究&#64022;之PPARγ增加肌內脂肪的堆積與PPARδ促進脂肪組織進行脂質分解的可行性。 本計畫的研究重點包括： 1. 添加六種脂肪酸於表現PPARγ之肌纖維母細胞，研究豬PPARγ之體內配體。 2. 研究可活化豬PPARγ之脂肪酸形成內源性配體之合成路徑。 3. 建立穩定表現PPARδ的C2C12 肌原纖維母細胞與3T3-L1 脂肪前身細胞供研究豬PPARδ於調控脂質代謝的角色。 4. 研究PPARδ與PPARγ間的交互作用及二者是否能合&#63882;調節肌原纖維母細胞分化成脂肪細胞及相關脂質代謝功能。 5. 分別產製肌肉組織特異表現PPARγ與脂肪組織特異表現PPARδ之轉基因小鼠，並育成帶有兩種轉基因之雙基因轉殖小鼠，以研究此二基因的功能。 6. 餵飼轉基因小鼠高量可活化PPARγ與PPARδ的脂肪酸之飼糧，以研究其對肌肉內脂肪堆積之影響。 <br> Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that promotes adipocyte differentiation and involved in regulating lipid metabolism. PPARδ is involved in lipid metabolism, specifically on lipolysis. In recent years, the function of rodent PPARs is well-study, whereas studies of the interaction of PPARγ and PPARδ are limited. In our previous studies, we demonstrated that porcine wild-type PPARγ and mutated PPARγ can both enhance the conversion of myoblasts into adipocytes and the ability to transdifferentiate was greater in cells containing the mutated PPARγ than in cells containing the wild-type PPARγ. It has been suggested that PPARδ has the ability to promote lipolysis in several species. Therefore, the current proposal is conducted to the function of porcine PPAR and PPAR and their endogenous ligands in adipocyte differentiation. Experiments are designed to study the ability of porcine PPARγ in increasing lipid accumulation in myoblasts and PPARδ in promoting lipolysis in adipose tissue in vivo. We propose this project to achieve the following research goals: 1. To identify precursors for endogenous ligands for porcine PPARγ using cells expressing PPARγ. 2. To study the synthetic pathway of endogenous ligands that derived from polyunsaturated fatty acids for PPARγ activation. 3. To establish ectopic expression of porcine PPARδ in C2C12 myoblasts and 3T3-L1 preadipocytes in order to study its role in lipid metabolism. 4. To study the interaction between PPARδ and PPARγ, and determine whether these two transcription factors work together to enhance the differentiation of adipocytes from myocytes 5. To generate transgenic mice that express mutated PPARγ in the muscle and PPARδ in the adipose tissue and double transgenic mice of these two genes. 6. To study the effect of myocytes transdifferentiate into adipocytes and lipolysis in adipose tissue in vivo by feeding transgenic mice with high fat diets to activate PPARs. Completion of this study will enhance our understanding on the gene and nutrient interaction involved in lipid metabolism and adipocyte differentiation. The ultimate goal of this proposal is to provide basic knowledge to regulate lipid accumulation in pigs and improve meat quality.Peroxisome proliferator-activated receptors (PPARs)lipid metabolismpigPeroxisome proliferator-activated receptors (PPARs)lipid metabolismpig