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

• DOI: 10.15252/embj.2023114086
• Publication Date: 2023-10-12T01:41:54Z
• Authors: Gabriela Krejčová; Cecilia Morgantini; Helena Zemanová; Volker M Lauschke; Julie Kovářová; Jiří Kubásek; Pavla Nedbalová; Nick Kamps‐Hughes; Martin Moos; Myriam Aouadi; Tomáš Doležal; Adam Bajgar
• Keywords: Mammals; Insulin-Like Growth Factor Binding Proteins; Insulin Antagonists; Macrophages; Animals; Insulin; Drosophila Proteins; Drosophila; Articles; Bacterial Infections; Insulin Resistance; 3. Good health

The immune response is an energy-demanding process that must be coordinated with systemic metabolic changes redirecting nutrients from stores to the system. Although this interplay fundamental for function of system, underlying mechanisms remain elusive. Our data show pro-inflammatory polarization Drosophila macrophages coupled production insulin antagonist ImpL2 through activity transcription factor HIF1α. production, reflecting nutritional demands activated macrophages, subsequently impairs signaling in fat body, thereby triggering FOXO-driven mobilization lipoproteins. This adaptation system and individual's resistance infection. We demonstrated analogically Drosophila, mammalian immune-activated produce homolog IGFBP7 a HIF1α-dependent manner enhanced by these cells induces lipoproteins hepatocytes. Hence, ImpL2/IGFBP7 represents evolutionarily conserved mechanism which alleviate central organ secure necessary their upon bacterial