APOB KINETICS IN HETEROZYGOUS LPL DEFICIENCY

杂合 LPL 缺陷中的 APOB 动力学

• 批准号: 2223712
• 负责人: DENNIS L SPRECHER
• 金额: $ 28.74万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-10 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2223712
• 关键词: apolipoproteins; blood lipoprotein metabolism; chylomicrons; coronary disorder; diet; dietary lipid; electrofocusing; enzyme activity; enzyme deficiency; enzyme linked immunosorbent assay; gel electrophoresis; heterozygote; human subject; lipoprotein lipase; low density lipoprotein; nutrition related tag; radiotracer; ultracentrifugation; very low density lipoprotein

It has been proposed that subjects with a partial deficiency of lipoprotein lipase (LpL) are more likely to develop premature coronary artery disease because they are predisposed to the expression of combined lipoprotein phenotypes. To elucidate the metabolic consequences of reduced LpL function, the production and catabolic rates of apoB-100 (LDL, IDL and VLDL), and apoB48 (chylomicrons/remnants) will be determined by the endogenous labeling, deuterated leucine technique in 15 LPL deficient heterozygotes. Bolus 13C-leucine will be administered simultaneously to clarify clearance rates. These results will be compared to historical controls (n=22). A pilot study using the same method will be performed on 3 Type I, LpL deficient subjects. They will be studied in the continuously fed state after dietary stabilization is achieved on an average American diet over a 4 week period. Lipoprotein composition including lipids and apolipoproteins (SDS-PAGE and ELISA assays) will be determined. Lipoprotein particle size will be determined by gradient gel electrophoresis. By performing these analyses, we hope to address the following issues: 1. Is the processing of VLDL to IDL to LDL compromised in LpL deficient subjects? 2. Is the production of apoB100 increased in LpL deficient heterozygotes compared to normal controls? 3. Does apoB48 catabolism diminish in LpL deficient subjects?

有人提出，部分缺乏 脂蛋白脂酶（LpL）更容易发生早发冠状动脉粥样硬化， 动脉疾病，因为他们倾向于表达组合 脂蛋白表型为了阐明减少的代谢后果， LpL功能、apoB-100（LDL、IDL和 VLDL）和apoB 48（乳糜微粒/残留物）将由 内源性标记，氘代亮氨酸技术在15 LPL缺陷 杂合子将同时给予13 C-亮氨酸推注， 澄清清除率。这些结果将与历史数据进行比较。 对照组（n=22）。将使用相同的方法进行初步研究， 3例I型LpL缺陷受试者。他们将在不断的研究 平均每个美国人在饮食稳定后达到进食状态， 饮食超过4周。脂蛋白组合物包括脂质和 将测定载脂蛋白（SDS-PAGE和ELISA测定）。 脂蛋白颗粒大小将通过梯度凝胶法测定 电泳通过进行这些分析，我们希望解决 下列问题： 1.在LpL缺乏的情况下，VLDL到IDL再到LDL的加工是否受损 科目？ 2. LpL缺陷杂合子中apoB 100的产生是否增加 与正常对照组相比，？ 3. apoB 48在LpL缺乏的受试者中是否减少？