Oxylipin transport by lipoprotein particles and its functional implications for cardiometabolic and neurological disorders

Authors: LIANG, NUANYI - University Of California, Davis; HARSCH, BRIAN - Pennsylvania State University; ZHOU, SITONG - University Of California, Davis; BORKOWSKA, ALISON - Pennsylvania State University; SHEARER, GREGORY - University Of California, Davis; KADDURAH-DAOUK, RIMA - Duke University; Newman, John; BORKOWSKI, KAMIL - University Of California, Davis

Submitted to: Progress in Lipid Research
Publication Type: Literature Review
Publication Acceptance Date: 11/13/2023
Publication Date: 11/17/2023
Citation: Liang, N., Harsch, B.A., Zhou, S., Borkowska, A.G., Shearer, G.C., Kaddurah-Daouk, R., Newman, J.W., Borkowski, K. 2023. Oxylipin transport by lipoprotein particles and its functional implications for cardiometabolic and neurological disorders. Progress in Lipid Research. 93. Article 101265. https://doi.org/10.1016/j.plipres.2023.101265.
DOI: https://doi.org/10.1016/j.plipres.2023.101265

Interpretive Summary: Lipoprotein particles in the blood stream are responsible for the movement of lipids around the body, where they influence oxidative stress and inflammation. The central nervous system (CNS) and the rest of the body have independent, but interacting lipoprotein systems. Impairment in lipoprotein metabolism is implicated in both cardiometabolic and neurodegenerative disorders. Oxylipins are modulators of inflammation and cell function known for their actions within cells. Oxylipins are also transported in lipoproteins. Understanding the influence of lipoportein oxylipins on cells of the body are just beginning, but have functional consequences in cardiometabolic disorders. Investigations of oxylipins in CNS lipoproteins are non-existent to date. However genetic variation in apolipoprotein E (ApoE), dysregulates lipoportein oxylipin levels and is the strongest known genetic association with Alzheimer’s disease. Therefore, such investigations will provide new perspectives on oxylipin- and lipoprotein-related disorders in the CNS. In this article, we reviews the existent literature to demonstrate the functional importance of lipoprotein particles in oxylipin transport, and argue that understanding the compartmentalization and dynamics of this process has the potential to fundamentally alter our consideration of lipoprotein particle structure and function in relation to cardiometabolic and neurodegenerative disorders.

Technical Abstract: Lipoprotein particles have well described impacts on oxidative stress and inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired lipoprotein metabolism is implicated in both cardiometabolic and neurodegenerative disorders. Despite substantial investigation into lipoprotein composition, structure and function, characterization of lipoprotein oxylipin profiles, their influence on lipoprotein functions, and their potential biological implications are just beginning. Lipoproteins contain the majority of oxylipins in the circulation, where they occur in both esterified and non-esterified forms incorporated either from cellular pools or by direct lipoprotein modification. Importantly, lipoprotein-mediated oxylipin transport allows for endocrine signaling by these lipid mediators, long considered to have only autocrine and paracrine functions. Changes in lipoprotein oxylipins have functional consequences, with the impact on inflammation by lipoprotein metabolizing cells demonstrated in the context of cardiometabolic disorders. Similar investigations of oxylipins in CNS lipoproteins are non-existent to date. However, as apolipoprotein E4 allele (APOE4) is associated with Alzheimer’s disease-related microglia dysfunction and oxylipin dysregulation, the exploration of ApoE4-lipoprotein oxylipins in AD development and progression is warranted. Such investigation is crucial to bridge the knowledge gap on the wide-spectrum oxylipin- and lipoprotein-related disorders in the peripheral and CNS. In this article, we review the existent literature to demonstrate the functional importance of lipoprotein particles in oxylipin transport, and argue that understanding the compartmentalization and dynamics of this process has the potential to fundamentally alter our consideration of lipoprotein particle structure and function in relation to cardiometabolic and neurodegenerative disorders.