OMEGA-3 FATTY ACIDS & HEPATIC LIPID METABOLISM

OMEGA-3 脂肪酸

• 批准号: 3355962
• 负责人: DAVID A OTTO
• 金额: $ 15.88万
• 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/3355962
• 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.

对富含鱼油的omega-3脂肪酸的兴趣， 研究表明， 消费有较低的冠心病死亡率。 这些人口 显示VLDL-甘油三酯和LDL-胆固醇降低。 它 认为降脂作用是由于 肝脏VLDL合成，但这种作用的机制不是 知道的 这项研究将测试一个工作假设，即欧米茄-3 脂肪酸通过直接抑制 脂肪酸合成，随后脂肪酸升高 氧化和由此产生的酰基辅酶A从 甘油三酯合成 这个假设的一个推论是， ω-3脂肪酸也会导致适应性降低， 肉毒碱棕榈酰转移酶I对抑制的敏感性 丙二酰1-CoA，以及过氧化物酶体的能力增加 脂肪酸氧化。 这一假设可能解释了 降低VLDL-甘油三酯和胆固醇，至少 部分，降低LDL-胆固醇。 此外，实验 旨在研究这些潜在的调制 其他饮食成分的影响。 拟议的实验 有三个具体目标。 1)初步实验将 比较以下物质的利用率和短期代谢效应： 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 ω-3）在分离的 肝细胞加或减胰岛素（在某些情况下加或减胰岛素） 吲哚美辛，一种前列腺素合成抑制剂）。 参数以 测量的是：14 C掺入脂肪酸氧化 来自外源性（1- 14 C）脂肪酸的产物和甘油三酯; 3 H 掺入脂肪酸、胆固醇和甘油三酯（来自 从头合成的脂肪酸）;和丙二酰-CoA。 过氧化物酶体氧化和结构的贡献 欧米茄-3脂肪酸的特点负责这些 效果将被确定。 2)EPA的短期影响 将确定其它脂肪酸的利用率。3)最后 鱼油摄入对肝脏脂质的长期适应性影响 将研究代谢。 本研究的意义 研究结果可能提供潜在的有用信息 关于CHD的饮食管理。