Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland.
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
Int J Epidemiol. 2022 Jun 13;51(3):996-1011. doi: 10.1093/ije/dyab156.
Quantitative lipoprotein analytics using nuclear magnetic resonance (NMR) spectroscopy is currently commonplace in large-scale studies. One methodology has become widespread and is currently being utilized also in large biobanks. It allows the comprehensive characterization of 14 lipoprotein subclasses, clinical lipids, apolipoprotein A-I and B. The details of these data are conceptualized here in relation to lipoprotein metabolism with particular attention on the fundamental characteristics of subclass particle numbers, lipid concentrations and compositional measures.
The NMR methodology was applied to fasting serum samples from Northern Finland Birth Cohorts 1966 and 1986 with 5651 and 5605 participants, respectively. All results were highly consistent between the cohorts. Circulating lipid concentrations in a particular lipoprotein subclass arise predominantly as the result of the circulating number of those subclass particles. The spherical lipoprotein particle shape, with a radially oriented surface monolayer, imposes size-dependent biophysical constraints for the lipid composition of individual subclass particles and inherently restricts the accommodation of metabolic changes via compositional modifications. The new finding that the relationship between lipoprotein subclass particle concentrations and the particle size is log-linear reveals that circulating lipoprotein particles are also under rather strict metabolic constraints for both their absolute and relative concentrations.
The fundamental structural and metabolic relationships between lipoprotein subclasses elucidated in this study empower detailed interpretation of lipoprotein metabolism. Understanding the intricate details of these extensive data is important for the precise interpretation of novel therapeutic opportunities and for fully utilizing the potential of forthcoming analyses of genetic and metabolic data in large biobanks.
利用核磁共振（NMR）光谱定量脂蛋白分析目前在大规模研究中很常见。有一种方法已经得到广泛应用，目前也在大型生物库中使用。它可以全面描述 14 种脂蛋白亚类、临床脂质、载脂蛋白 A-I 和 B。这里根据脂蛋白代谢的概念来描述这些数据的细节，特别关注亚类颗粒数、脂质浓度和组成测量的基本特征。
该 NMR 方法应用于分别来自芬兰北部出生队列 1966 年和 1986 年的 5651 名和 5605 名参与者的空腹血清样本。两个队列之间的所有结果都高度一致。特定脂蛋白亚类中的循环脂质浓度主要是由于这些亚类颗粒的循环数量而产生的。球形脂蛋白颗粒形状，具有径向取向的表面单层，对单个亚类颗粒的脂质组成施加尺寸依赖性的生物物理限制，并固有地限制通过组成修饰来适应代谢变化。脂蛋白亚类颗粒浓度与颗粒大小之间的关系呈对数线性的新发现表明，循环脂蛋白颗粒的绝对浓度和相对浓度也受到相当严格的代谢限制。
本研究阐明的脂蛋白亚类之间的基本结构和代谢关系赋予了脂蛋白代谢的详细解释能力。理解这些广泛数据的复杂细节对于准确解释新的治疗机会以及充分利用大型生物库中遗传和代谢数据分析的潜力非常重要。
