LIPOPROTEIN COMPOSITION AND METABOLISM IN PIMA INDIANS

皮马印第安人的脂蛋白组成和代谢

• 批准号: 4690044
• 负责人: B V HOWARD
• 金额: --
• 依托单位: NAT INST OF ARTHRITIS, DIABETES, DIGESTIVE & KIDNEY DISEASES
• 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/4690044
• 关键词: Native Americans; apolipoproteins; blood lipoprotein metabolism; cardiovascular disorder epidemiology; high density lipoproteins; hormone regulation /control mechanism; human subject; insulin; low density lipoprotein; male; obesity; population genetics; radiotracer; very low density lipoprotein

Pima Indians have a high prevalence of obesity, diabetes mellitus and hyperinsulinemia, but they have low plasma cholesterol levels, reduced low density lipoprotein (LDL) and high density lipoprotein (HDL), and decreased incidence of cardiovascular disease (CVD). Lipoprotein composition and metabolism in Pima Indians are being investigated in order to further understand control of lipoprotein metabolism and how lipoproteins are related to obesity and CVD. The studies of lipoprotein composition indicate there may be racial differences in lipoprotein distributions which may be important in the prevalence of CVD. Simultaneous studies have been performed of very low density lipoprotein (VLDL) apoB and LDL apoB metabolism using a double isotope procedure. In addition, a multicompartmental model has been developed for the analysis of kinetic data for the simultaneous measure of VLDL, IDL and LDL apoB metabolism. Studies in a group of male Pimas indicated that obesity results in a greatly increased flux of VLDL apoB. LDL apoB levels were not elevated in the obese subjects, because of both increased metabolism of VLDL through the alternate pathway and increased catabolism of LDL. Comparison of apoB metabolism in Pimas and weight-matched Caucasians indicated that the low LDL in Pimas is related to both higher FCR for LDL and higher proportion of VLDL metabolized without conversion of LDL. Further, VLDL "shunt" and LDL FCR appeared to be correlated. The results of lipoprotein metabolic studies in Pimas to date suggest a large flux of substrates and regulators (i.g. insulin) which cause over production of lipoproteins, but that compensatory mechanisms are operative which result in maintenance of low plasma concentrations.

皮马印第安人的肥胖、糖尿病和糖尿病患病率很高， 高胰岛素血症，但他们有低血浆胆固醇水平，降低低 高密度脂蛋白（HDL），并降低 心血管疾病（CVD）的发病率。 脂蛋白组成和 正在研究皮马印第安人的新陈代谢， 了解脂蛋白代谢的控制和脂蛋白是如何 与肥胖和心血管疾病有关 脂蛋白组成的研究 表明脂蛋白分布可能存在种族差异， 可能对CVD的流行很重要。 同时进行的研究非常低密度脂蛋白 （VLDL）apoB和LDL apoB代谢。 在 此外，还开发了多房室模型，用于分析 同时测量VLDL、IDL和LDL apoB的动力学数据 新陈代谢. 对一组雄性皮马的研究表明，肥胖 导致VLDL apoB的流量大大增加。 低密度脂蛋白载脂蛋白B水平不是 在肥胖受试者中升高，因为代谢增加， VLDL通过交替途径和增加LDL的催化剂。 Pimas与体重匹配的白种人apoB代谢的比较 表明，低LDL在皮马斯是相关的高FCR为LDL VLDL代谢比例较高，LDL未转化。 此外，VLDL“分流”和LDL FCR似乎是相关的。 结果 迄今为止，皮马斯的脂蛋白代谢研究表明， 底物和调节剂（例如，胰岛素），导致过度生产 脂蛋白，但代偿机制是有效的， 维持低血浆浓度。