West Coast Metabolomics Center, Genome Center, University of California Davis, Davis, CA 95616, USA.
Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
Prog Lipid Res. 2024 Jan;93:101265. doi: 10.1016/j.plipres.2023.101265. Epub 2023 Nov 17.
Lipoprotein metabolism is critical to inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired lipoprotein metabolism is implicated in both cardiometabolic and neurological disorders. Despite the substantial investigation into the composition, structure and function of lipoproteins, the lipoprotein oxylipin profiles, their influence on lipoprotein functions, and their potential biological implications are unclear. Lipoproteins carry most of the circulating oxylipins. Importantly, lipoprotein-mediated oxylipin transport allows for endocrine signaling by these lipid mediators, long considered to have only autocrine and paracrine functions. Alterations in plasma lipoprotein oxylipin composition can directly impact inflammatory responses of lipoprotein metabolizing cells. Similar investigations of CNS lipoprotein oxylipins are non-existent to date. However, as APOE4 is associated with Alzheimer's disease-related microglia dysfunction and oxylipin dysregulation, ApoE4-dependent lipoprotein oxylipin modulation in neurological pathologies is suggested. Such investigations are crucial to bridge knowledge gaps linking oxylipin- and lipoprotein-related disorders in both periphery and CNS. Here, after providing a summary of existent literatures on lipoprotein oxylipin analysis methods, we emphasize the importance of lipoproteins in oxylipin transport and argue that understanding the compartmentalization and distribution of lipoprotein oxylipins may fundamentally alter our consideration of the roles of lipoprotein in cardiometabolic and neurological disorders.
脂蛋白代谢对炎症至关重要。虽然外周组织和中枢神经系统 (CNS) 有独立但相互连接的脂蛋白系统，但脂蛋白代谢受损与心脏代谢和神经紊乱都有关联。尽管人们对脂蛋白的组成、结构和功能进行了大量研究，但脂蛋白氧化脂质谱、它们对脂蛋白功能的影响及其潜在的生物学意义尚不清楚。脂蛋白携带大部分循环氧化脂质。重要的是，脂蛋白介导的氧化脂质转运允许这些脂质介质进行内分泌信号传递，这些脂质介质长期以来被认为只具有自分泌和旁分泌功能。血浆脂蛋白氧化脂质组成的改变会直接影响脂蛋白代谢细胞的炎症反应。迄今为止，对中枢神经系统脂蛋白氧化脂质的类似研究还不存在。然而，由于 APOE4 与阿尔茨海默病相关的小胶质细胞功能障碍和氧化脂质失调有关，因此提出了 ApoE4 依赖性脂蛋白氧化脂质在神经病理学中的调节作用。这些研究对于弥合与外周组织和中枢神经系统中与氧化脂质和脂蛋白相关的疾病相关的知识差距至关重要。在这里，在提供了关于脂蛋白氧化脂质分析方法的现有文献综述之后，我们强调了脂蛋白在氧化脂质转运中的重要性，并认为理解脂蛋白氧化脂质的区室化和分布可能从根本上改变我们对脂蛋白在心脏代谢和神经紊乱中的作用的考虑。
