Hildebrand Staffan, Löwa Norbert, Paysen Hendrik, Fratila Raluca M, Reverte-Salisa Laia, Trakoolwilaiwan Thithawat, Niu Zheming, Kasparis Georgios, Preuss Stephanie Franziska, Kosch Olaf, M de la Fuente Jesus, Thanh Nguyen Thi Kim, Wiekhorst Frank, Pfeifer Alexander
Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
8.23 Metrology for Magnetic Nanoparticles, Physikalisch-Technische Bundesanstalt, Abbestraße 2-12, 10587 Berlin, Germany.
ACS Nano. 2021 Jan 26;15(1):434-446. doi: 10.1021/acsnano.0c03229. Epub 2020 Dec 11.
Lipids are a major source of energy for most tissues, and lipid uptake and storage is therefore crucial for energy homeostasis. So far, quantification of lipid uptake has primarily relied on radioactive isotope labeling, exposing human subjects or experimental animals to ionizing radiation. Here, we describe the quantification of uptake of chylomicrons, the primary carriers of dietary lipids, in metabolically active tissues using magnetic particle imaging (MPI) and magnetic particle spectroscopy (MPS). We show that loading artificial chylomicrons (ACM) with iron oxide nanoparticles (IONPs) enables rapid and highly sensitive detection of lipid uptake using MPS. Importantly, by utilizing highly magnetic Zn-doped iron oxide nanoparticles (ZnMNPs), we generated ACM with MPI tracer properties superseding the current gold-standard, Resovist, enabling quantification of lipid uptake from whole-animal scans. We focused on brown adipose tissue (BAT), which dissipates heat and can consume a large part of nutrient lipids, as a model for tightly regulated and inducible lipid uptake. High BAT activity in humans correlates with leanness and improved cardiometabolic health. However, the lack of nonradioactive imaging techniques is an important hurdle for the development of BAT-centered therapies for metabolic diseases such as obesity and type 2 diabetes. Comparison of MPI measurements with iron quantification by inductively coupled plasma mass spectrometry revealed that MPI rivals the performance of this highly sensitive technique. Our results represent radioactivity-free quantification of lipid uptake in metabolically active tissues such as BAT.
脂质是大多数组织的主要能量来源，因此脂质摄取和储存对于能量稳态至关重要。到目前为止，脂质摄取的定量主要依赖于放射性同位素标记，这会使人类受试者或实验动物暴露于电离辐射。在这里，我们描述了使用磁粒子成像（MPI）和磁粒子光谱（MPS）对代谢活跃组织中乳糜微粒（膳食脂质的主要载体）摄取进行定量的方法。我们表明，用氧化铁纳米颗粒（IONPs）装载人工乳糜微粒（ACM）能够使用MPS快速且高度灵敏地检测脂质摄取。重要的是，通过利用高磁性的锌掺杂氧化铁纳米颗粒（ZnMNPs），我们生成了具有MPI示踪特性的ACM，其性能超过了当前的金标准Resovist，能够从全动物扫描中定量脂质摄取。我们将重点放在棕色脂肪组织（BAT）上，它能够散热并消耗大部分营养脂质，作为严格调控和诱导脂质摄取的模型。人类BAT的高活性与瘦体重和改善的心脏代谢健康相关。然而，缺乏非放射性成像技术是开发以BAT为中心的代谢疾病（如肥胖症和2型糖尿病）治疗方法的一个重要障碍。通过电感耦合等离子体质谱法对MPI测量结果与铁定量进行比较，结果表明MPI的性能可与这种高灵敏度技术相媲美。我们的结果代表了对BAT等代谢活跃组织中脂质摄取进行无放射性定量。
