OMEGA-3 FATTY ACIDS & HEPATIC LIPID METABOLISM

OMEGA-3 脂肪酸

• 批准号: 3355963
• 负责人: DAVID A OTTO
• 金额: $ 16.12万
• 依托单位: BAPTIST HEALTH SYSTEM, INC.
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3355963
• 关键词: acyl coA; acyltransferase; atherosclerosis; blood lipoprotein metabolism; chemical structure function; cholesterol; dietary carbohydrates; dietary lipid; fatty acid metabolism; indomethacin; insulin; laboratory rat; lipid metabolism; liver cells; liver metabolism; marine animal oil; nutrition related tag; omega 3 fatty acid; palmitates; peroxisome; radiotracer; steroid biosynthesis; triglycerides; tritium; unsaturated fatty acids; vegetable oils; very low density lipoprotein

Interest in omega-3 fatty acids, high in fish oil, stems in part from studies indicating that populations with high fish consumption have lower mortality from CHD. These populations demonstrate reduced VLDL-triglycerides and LDL-cholesterol. It is believed that the lipid-lowering effects are due to a decrease in hepatic VLDL synthesis, but the mechanism for this action is not known. This research will test a working hypothesis that omega-3 fatty acids decrease VLDL synthesis through a direct inhibition of fatty acid synthesis with subsequent elevation of fatty acid oxidation and a resulting diversion of acyl-CoA away from triglyceride synthesis. A corollary to this hypothesis is that omega-3 fatty acids also cause an adaptive decrease in the sensitivity of carnitine palmitoyltransferase I to inhibition by malony1-CoA, and an increase in the capacity for peroxisomal fatty acid oxidation. This hypothesis can potentially explain the reduction in VLDL-triglycerides and cholesterol and, at least in part, the reduction in LDL-cholesterol. In addition, experiments are designed to investigate the potential modulation of these effects by other dietary components. The proposed experiments have three specific objectives. 1) Initial experiments will compare the utilization and short-term metabolic effects of palmitic acid, linoleic acid, eicosapentaenoic acid (C20:5 omega- 3), and docosahexaenoic acid (C22:6 omega-3) in isolated hepatocytes plus or minus insulin (and in some cases plus or minus indomethacin, a prostaglandin synthesis inhibitor). Parameters to be measured are: 14C incorporation into fatty acid oxidation products and triglycerides from exogenous (1-14C) fatty acids; 3H incorporation into fatty acids, cholesterol and triglycerides (from de novo synthesized fatty acid) from 3H2O; and malonyl-CoA. The contribution of peroxisomal oxidation and the structural characteristics of the omega-3 fatty acid responsible for these effects will be determined. 2) Short-term effects of EPA on the utilization of other fatty acids will be determined. 3) Finally, the long-term adaptive effects of fish oil consumption on hepatic lipid metabolism will be investigated. The significance of this research is that the results may provide potentially useful information concerning the dietary management of CHD.

人们对富含鱼油的omega-3脂肪酸的兴趣部分源于 研究表明，鱼类数量较多的种群 消费有较低的冠心病死亡率。这些人口 表现出极低密度脂蛋白-甘油三酯和低密度脂蛋白-胆固醇的降低。它 据认为，降脂作用是由于减少了 肝脏极低密度脂蛋白的合成，但这种作用的机制不是 为人所知。这项研究将检验一个有效的假设，即omega-3 脂肪酸通过直接抑制极低密度脂蛋白的合成而减少VLDL的合成 脂肪酸合成与随后的脂肪酸升高 氧化和由此导致的酰基辅酶A从 甘油三酯合成。这一假设的推论是 Omega-3脂肪酸也会导致体内 肉毒碱棕榈酰转移酶I对卡尼汀抑制的敏感性 丙二醛1-辅酶A和过氧化物体能力的增加 脂肪酸氧化。这一假设可以潜在地解释 极低密度脂蛋白-甘油三酯和胆固醇的降低，至少在 部分，低密度脂蛋白-胆固醇的降低。此外，实验， 旨在研究这些基因的潜在调制 其他饮食成分的影响。拟议中的实验 有三个具体目标。1)初步实验将 比较两种药物的利用率和短期代谢效果 棕榈酸、亚油酸、二十碳五烯酸(C20：5 omega- 3)和二十二碳六烯酸(C22：6 omega-3) 肝细胞加或减胰岛素(在某些情况下加或减 吲哚美辛，一种前列腺素合成抑制剂)。参数设置为 需要测量的是：~(14)C掺入脂肪酸氧化 外源(1-14C)脂肪酸的产物和甘油三酯； 含有脂肪酸、胆固醇和甘油三酯(来自 从头合成脂肪酸)和丙二酰辅酶A。 过氧化体氧化的贡献与结构 引起这些变化的omega-3脂肪酸的特征 效果将会确定。2)环境保护局的短期影响 其他脂肪酸的利用将被确定。3)最后， 食用鱼油对肝脏脂质的长期适应性影响 将对新陈代谢进行研究。这项研究的意义 结果可能会提供潜在有用的信息 关于冠心病的饮食管理。