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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Glucosamine increases macrophage lipid accumulation by regulating the mammalian target of rapamycin signaling pathway

  • Sang-Min Kim (Department of Biomedical Science, Program in Biomedical Science and Engineering, Inha University) ;
  • Dong Yeol Kim (Department of Biomedical Science, Program in Biomedical Science and Engineering, Inha University) ;
  • Jiwon Park (Department of Biomedical Science, Program in Biomedical Science and Engineering, Inha University) ;
  • Young-Ah Moon (Department of Molecular Medicine, College of Medicine, Inha University) ;
  • Inn-Oc Han (Department of Biomedical Science, Program in Biomedical Science and Engineering, Inha University)
  • Received : 2023.08.31
  • Accepted : 2023.11.03
  • Published : 2024.02.29
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Abstract

Elevated blood glucose is associated with an increased risk of atherosclerosis. Data from the current study showed that glucosamine (GlcN), a normal glucose metabolite of the hexosamine biosynthetic pathway (HBP), promoted lipid accumulation in RAW264.7 macrophage cells. Oleic acid- and lipopolysaccharide (LPS)-induced lipid accumulation was further enhanced by GlcN in RAW264.7 cells, although there was no a significant change in the rate of fatty acid uptake. GlcN increased acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), scavenger receptor class A, liver X receptor, and sterol regulatory element-binding protein-1c (SREBP-1c) mRNA expression, and; conversely, suppressed ATP-binding cassette transporter A1 (ABCA-1) and ABCG-1 expression. Additionally, GlcN promoted O-GlcNAcylation of nuclear SREBP-1 but did not affect its DNA binding activity. GlcN stimulated phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase. Rapamycin, a mTOR-specific inhibitor, suppressed GlcN-induced lipid accumulation in RAW264.7 cells. The GlcN-mediated increase in ACC and FAS mRNA was suppressed, while the decrease in ABCA-1 and ABCG-1 by GlcN was not significantly altered by rapamycin. Together, our results highlight the importance of the mTOR signaling pathway in GlcN-induced macrophage lipid accumulation and further support a potential link between mTOR and HBP signaling in lipogenesis.

Keywords

Acknowledgement

This work was supported by National Research Foundation (NRF) of Korea Grants (NRF-2021R1A2C1012480) and research grant of Inha University.

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