Number of the records: 1  

Macrophage-derived insulin antagonist ImpL2 induces lipoprotein mobilization upon bacterial infection

  1. 1.
    0580499 - BC 2024 RIV US eng J - Journal Article
    Krejčová, G. - Morgantini, C. - Zemanova, H. - Lauschke, V.M. - Kovářová, Julie - Kubásek, J. - Nedbalová, P. - Kamps-Hughes, N. - Moos, Martin - Aouadi, M. - Doležal, T. - Bajgar, A.
    Macrophage-derived insulin antagonist ImpL2 induces lipoprotein mobilization upon bacterial infection.
    EMBO Journal. Roč. 42, OCT (2023), č. článku e114086. ISSN 0261-4189. E-ISSN 1460-2075
    Institutional support: RVO:60077344
    Keywords : kupffer cells * fat-body * drosophila * metabolism * storage * particles * delivery * system * sirna * Drosophila * ImpL2 * insulin resistance * lipoproteins * macrophage polarization
    OECD category: Biochemistry and molecular biology
    Impact factor: 11.4, year: 2022
    Method of publishing: Open access
    https://www.embopress.org/doi/epdf/10.15252/embj.2023114086

    The immune response is an energy-demanding process that must be coordinated with systemic metabolic changes redirecting nutrients from stores to the immune system. Although this interplay is fundamental for the function of the immune system, the underlying mechanisms remain elusive. Our data show that the pro-inflammatory polarization of Drosophila macrophages is coupled to the production of the insulin antagonist ImpL2 through the activity of the transcription factor HIF1 alpha. ImpL2 production, reflecting nutritional demands of activated macrophages, subsequently impairs insulin signaling in the fat body, thereby triggering FOXO-driven mobilization of lipoproteins. This metabolic adaptation is fundamental for the function of the immune system and an individual's resistance to infection. We demonstrated that analogically to Drosophila, mammalian immune-activated macrophages produce ImpL2 homolog IGFBP7 in a HIF1 alpha-dependent manner and that enhanced IGFBP7 production by these cells induces mobilization of lipoproteins from hepatocytes. Hence, the production of ImpL2/IGFBP7 by macrophages represents an evolutionarily conserved mechanism by which macrophages alleviate insulin signaling in the central metabolic organ to secure nutrients necessary for their function upon bacterial infection.
    Permanent Link: https://hdl.handle.net/11104/0349276

     
     
Number of the records: 1  

  This site uses cookies to make them easier to browse. Learn more about how we use cookies.