METABOLISM OF APOA-IV IN HUMANS

APOA-IV 在人体中的代谢

• 批准号: 3858031
• 负责人: D J RADER
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3858031
• 关键词: apolipoproteins; blood lipoprotein metabolism; heterozygote; high density lipoproteins; homozygote; human middle age (35-64); human subject; hypertriglyceridemia; lipid metabolism; protein sequence; radiotracer; stable isotope diagnosis; triglycerides; young adult human (21-34)

Apolipoprotein (apo) A-IV is associated with both triglyceride-rich lipoproteins (TRL) and high density lipoproteins (HDL). Though its precise role is poorly understood, it has been proposed to be involved in both triglyceride metabolism as well as reverse cholesterol transport. ApoA-IV is a polymorphic protein, and the molecular basis for all four major isoforms has been identified. The apoA-IV-2 isoprotein has been associated with lower triglyceride and higher HDL levels than the most common apoA-IV-l isoprotein. Both forms have been studied kinetically in several subjects, including six heterozygotes for apoA-IV-1/2 and one homozygote for apoA-IV-2/2. The apoA-IV-2 form has a significantly slower catabolic rate than the apoA-IV-l form, and in the homozygote was markedly slower. ApoA-l metabolism in the apoA-IV-2/2 homozygote was normal. This provides new insight into the mechanism of the higher HDL levels associated with apoA-IV-2. ApoA-IV plasma levels have been found to be positively associated with plasma triglyceride levels, whereas levels of apoA-l are inversely correlated. The metabolic explanation of this association was determined by studying the metabolism of apoA-IV and apoA-l in subjects with hypertriglyceridemia compared with normal subjects. Both exogenously-labeled radiotracers and endogenous labeling with stable isotopes were utilized. In the hypertriglyceridemic patients, the catabolic rate of apoA-IV was markedly delayed compared with normal, despite an increase in the rate of apoA-l catabolism. Hence, hypertriglyceridemia has opposite effects on apoA-IV and apoA-l catabolism, despite the close association of these apolipoproteins in plasma. The higher apoA-IV levels seen with higher levels of triglycerides are due to a delay in the rate of apoA-IV catabolism, rather than an increased synthetic rate of this apolipoprotein. These studies included subjects of age 20 to 55 years. Forty percent of the subjects in these studies were women. The studies included one African-American, one Hispanic, and two Asian subjects.

载脂蛋白(Apo)A-IV与富含甘油三酯 脂蛋白(TRL)和高密度脂蛋白(HDL)。尽管它的 人们对它的确切作用知之甚少，它被提议参与到 甘油三酯代谢和胆固醇的反向运输。 载脂蛋白A-IV是一种多态蛋白，也是这四种蛋白的分子基础 已经确定了主要的同工酶。ApoA-IV-2同工蛋白已被 与更低的甘油三酯和更高的高密度脂蛋白水平有关 共同的载脂蛋白A-IV-L同工蛋白。这两种形式都已在 几个受试者，包括6个apoA-IV-1/2杂合子和1个 ApoA-IV-2/2纯合子。apoA-IV-2形式显著 分解速度慢于载脂蛋白A-IV-L形式，纯合子中为 明显慢了很多。载脂蛋白A-IV-2/2纯合子中载脂蛋白A-L的代谢 很正常。这为更高密度脂蛋白的作用机制提供了新的见解 与载脂蛋白A-IV-2相关的水平。 已发现载脂蛋白A-IV血浆水平与 与血浆甘油三酯水平呈正相关，而载脂蛋白A-L水平则相反 相互关联。确定了这种联系的代谢解释。 通过对高脂血症患者载脂蛋白A-IV和载脂蛋白A-L代谢的研究 高甘油三酯血症与正常人比较。两者都有 外源标记的放射性示踪剂和稳定的内源性标记 利用了同位素。在高甘油三酯血症患者中， 载脂蛋白A-IV的分解速度明显慢于正常， 尽管载脂蛋白A-L分解代谢率增加。因此， 高甘油三酯血症对载脂蛋白A-IV和载脂蛋白A-L的相反作用 分解代谢，尽管这些载脂蛋白在 血浆。较高的载脂蛋白A-IV水平与较高的 甘油三酯是由于载脂蛋白A-IV分解代谢速度的延迟， 而不是增加这种载脂蛋白的合成速度。 这些研究对象的年龄在20岁到55岁之间。四十 在这些研究中，百分之百的受试者是女性。这些研究 包括一名非裔美国人，一名西班牙裔和两名亚洲人。