2001-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/694089摘要：本研究的目的在應用體外培養豬的脂肪前身細胞 (stromal/vascular cells), 來研究脂肪細胞的分化情形，並探討長鏈多不飽和脂肪酸如何影響諸多參與調控脂肪代謝之基因的表達機制。最近研究指出，長鏈多不飽和脂肪酸會減少大鼠的肝臟中轉錄因子 ADD1 (adipocyte determination differentiation dependant factor 1) 的表達。轉錄因子 ADD1 已知會增強涉及脂肪新生合成基因（脂肪酸合成&#37238;-FAS和 glycerol-3- phosphate acyltransferase）的表現，在豬的脂肪組織中，FAS負責脂肪酸新生合成，所以與脂肪組織中脂肪堆積有密切的關係。因此，長鏈多不飽和脂肪酸當能因減少ADD1的表達而有效減少脂肪酸和脂肪合成活性，從而達成降低脂肪堆積之目的。 在豬的脂肪組織中 ADD1和 FAS mRNA之含量遠高於肝者，且已有試驗證據顯示，飼糧中之多不飽和脂肪酸可以堆積於脂肪組織，因此攝入之多不飽和脂肪酸 可能可以影響脂肪細胞之ADD1，進而影響FAS之表達。 本研究室已建立一套豬的脂肪前身細<br> Abstract: A porcine preadipocyte cell (Stromal/vascular cell-S/V cell) culture system will be utilized to determine the mechanism by which polyunsaturated fatty acids (PUFA) reduce the expression of genes involved in lipid metabolism and adipocyte differentiation. Recent studies showed that in rat liver, PUFA decrease expression of the transcription factor, adipocyte determination differentiation dependant factor 1 (ADD1). The ADD1 increases the expression of genes for lipid synthesis (fatty acid synthase-FAS and glycerol-3-phosphate acyltransferase). In pigs, FAS involves in fatty acid de novo synthesis in adipose tissue. Therefore, it has an important role for fat deposition in adipose tissue. The overall effects of PUFA could reduce the expression of ADD1 through which FA and fat synthesis will be reduced. This will then decrease the fat deposition in pigs. In pigs, ADD1 and FAS mRNA abundance is greater in adipose tissue than in liver. It has been shown that dietary PUFA could be deposited in adipose tissue, suggesting dietary PUFA could assert their effects on ADD1 and FAS in pig adipose tissue. We have set up a pig preadipocyte cell culture system, which can be utilized to study the molecular mechanism in adipocyte differentiation. In pig S/V cells, several PUFA (conjugated linoleic acid, arachidonic acid-AA, and docosahexaenoic acid-DHA) decrease expression of ADD1. It has been shown that PUFA inhibit FAS mRNA in rat hepatocytes due to a production of FA peroxides from PUFA. However, the mechanism to regulate the expression of ADD1 in porcine adipocytes is yet to be elucidated. Utilizing porcine S/V cell culture model, proposed studies will determine: 1. whether the mechanism by which DHA decreases ADD1 is through a production of FA peroxides; 2. the effect of different PUFA (AA and DHA) on ADD1, FAS, superoxide dismutase, and glutathione reductase; 3. whether vitamine E attenuates the effect of DHA on reducing the expression of ADD1 and FAS; 4. whether AA and DHA affect the expression of ADD1 and FAS through their metabolites. Taken together, the proposed studies will identify molecular mechanisms by which PUFA assert their function. The results should be able to provide new information to develop new strategies toward reducing overall body fat deposition in pigs.豬脂肪細胞長鏈多不飽和脂肪酸Pigadipocytepolyunsaturated fatty acid