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Comprehensive Lipid Profiling Recapitulates Enhanced Lipolysis and Fatty Acid Metabolism in Intimal Foamy Macrophages From Murine Atherosclerotic Aorta

  • Jae Won Seo (Department of Chemistry, Yonsei University) ;
  • Kyu Seong Park (Department of Life Science, Research Institute for Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, College of Natural Sciences, Hanyang University) ;
  • Gwang Bin Lee (Department of Chemistry, Yonsei University) ;
  • Sang-eun Park (Department of Life Science, Research Institute for Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, College of Natural Sciences, Hanyang University) ;
  • Jae-Hoon Choi (Department of Life Science, Research Institute for Natural Sciences, Hanyang Institute of Bioscience and Biotechnology, College of Natural Sciences, Hanyang University) ;
  • Myeong Hee Moon (Department of Chemistry, Yonsei University)
  • Received : 2023.02.20
  • Accepted : 2023.05.21
  • Published : 2023.08.31
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Abstract

Lipid accumulation in macrophages is a prominent phenomenon observed in atherosclerosis. Previously, intimal foamy macrophages (FM) showed decreased inflammatory gene expression compared to intimal non-foamy macrophages (NFM). Since reprogramming of lipid metabolism in macrophages affects immunological functions, lipid profiling of intimal macrophages appears to be important for understanding the phenotypic changes of macrophages in atherosclerotic lesions. While lipidomic analysis has been performed in atherosclerotic aortic tissues and cultured macrophages, direct lipid profiling has not been performed in primary aortic macrophages from atherosclerotic aortas. We utilized nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry to provide comprehensive lipid profiles of intimal non-foamy and foamy macrophages and adventitial macrophages from Ldlr-/- mouse aortas. We also analyzed the gene expression of each macrophage type related to lipid metabolism. FM showed increased levels of fatty acids, cholesterol esters, phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol, and sphingomyelin. However, phosphatidylethanolamine, phosphatidic acid, and ceramide levels were decreased in FM compared to those in NFM. Interestingly, FM showed decreased triacylglycerol (TG) levels. Expressions of lipolysis-related genes including Pnpla2 and Lpl were markedly increased but expressions of Lpin2 and Dgat1 related to TG synthesis were decreased in FM. Analysis of transcriptome and lipidome data revealed differences in the regulation of each lipid metabolic pathway in aortic macrophages. These comprehensive lipidomic data could clarify the phenotypes of macrophages in the atherosclerotic aorta.

Keywords

Acknowledgement

This work was supported by the National Research Foundation (NRF) of Korea (NRF-2021R1A2C2003171, 2021R1A2C3004586, RS-2023-00207840, and 2016M3A9D5A01952413).

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