Abstract
摘要:
應用體外培養豬的脂肪前身細胞來研究脂肪細胞分化情形發現(NSC90- 2313-B-002-304),二十二碳六烯酸(DHA)能抑制ADD/SREBP的表現。轉錄因子ADD可促進脂肪酸合成酶、甘油三磷酸醯化酶與HMG CoA reductase等參與脂肪與膽固醇合成基因的表現。活體試驗如經證實具相同之效果,將可提供減少豬隻脂肪與膽固醇堆積之可行途徑。利用富含高DHA (44 %)的海藻油產品可強化組織DHA堆積並避免產品具魚腥味。 本計畫研究重點包括:
1. 選殖豬隻ADD2、 HMG CoA reductase與LDL receptor的基因片段。轉錄因子 ADD2可調節肝中膽固醇代謝基因之表達(HMG CoA reductase、LDL receptor)。
2. 測量飼糧DHA對ADD1、ADD2、HMG CoA reductase與LDL receptor在豬隻肝臟與脂肪組織間的表現情形。我們將同時評估ADD1與ADD2在mRNA與其成熟蛋白質的表現量。
3. 測量飼糧DHA對PPARα 與acyl CoA oxidase (ACO)在豬隻
Abstract: The effect of dietary docosahexaenoic acid on the expression of genes involved in lipid metabolism in pigs
Keywords:Pig, docosahexaenoic acid, ADD/SREBP, lipid metabolism, cholesterol.
Docosahexaenoic acid (DHA) inhibits the expression of adipocyte differentiation determination factor/sterol regulatory enhancer binding protein (ADD/SREBP) in porcine stromal vascular cells during adipocyte differentiation in vitro (NSC90-2313-B-002-304). The ADD/SREBP is a group of transcription factors that increase the expression of several lipogenic and cholesterogenic genes, such as fatty acid synthase, glycerol-3-phosphate acyltransferase, and HMG CoA reductase. They have an important role for regulating fat deposition in adipose tissue. The overall effects of DHA could reduce the expression of ADD and other genes through which lipogenesis and cholesterolgenesis will be reduced. The same effect if demonstrated in vivo, will provide a new approach to reduce lipogenesis and cholesterogenesis in pigs. Therefore, the current proposal is conducted to evaluate the effect of dietary DHA on the expression of genes involved in lipid metabolism in pigs.
Utilizing algal oil product that contains very high DHA (44 %) to enrich DHA has the potential to enrich tissue DHA and avoid the fish order concern when use fish oil in the diet. We propose this project to achieve the following research goals:
1. To clone fragments of porcine ADD2, HMG CoA reductase, and LDL receptor genes. The ADD2 is a transcription factor in liver that is responsible for regulating the expression of HMG CoA reductase and LDL receptor, two primary genes involved in cholesterol metabolism.
2. To measure the effect of dietary DHA on the expression of ADD1, ADD2, HMG CoA reductase, and LDL receptor in porcine liver or adipose tissue. We will measure the expression of ADD1 and ADD2 both at mRNA and mature protein concentrations.
3. To measure the effect of dietary DHA on the expression of peroxisome proliferators activated receptor alpha (PPAR) and acyl CoA oxidase (ACO) in porcine liver and skeletal muscle. The PPAR is a transcription factor that regulates fatty acid oxidation enzymes (eg., ACO) in the liver and skeletal muscle.
4. To explore and clone possible genes by which dietary DHA regulates lipid metabolism in porcine liver.
5. To explore and clone possible genes by which DHA regulates lipid metabolism in porcine adipose tissue.
This study in vivo will enhance our understanding on the genes involved in DHA function and lead to understand the basic mechanisms by which DHA inserts its functions. The ultimate goal of this proposal is to provide basic knowledge to help define appropriate amounts of dietary DHA for pigs and to explore a better understanding of the involvement of genes in lipid and cholesterol metabolism and reducing body fat. The knowledge will provide new strategies to improve nutrient utilization and create better animal meat products.
Keyword(s)
豬
二十二碳六烯酸
ADD/SREBP
脂質代謝
膽固醇。
Pig
DHA
ADD/SREBP
lipid metabolism
cholesterol