Supplementary Material for: Perilipin1 deficiency prompts lipolysis in lipid droplets and aggravates the pathogenesis of persistent immune activation in Drosophila

Lipid droplets (LDs) are highly dynamic intracellular organelles, which are involved in lots of biological processes. However, the dynamic morphogenesis and functions of intracellular LDs during persistent innate immune responses remain obscure. In this study, we induce long-term systemic immune activation in Drosophila through genetic manipulation. Then, the dynamic pattern of LDs is traced in the Drosophila fat body. We find that deficiency of Plin1, a key regulator of LDs’ reconfiguration, blocks LDs minimization at the initial stage of immune hyperactivation but enhances LDs breakdown at the later stage of sustained immune activation via recruiting the lipase Brummer (Bmm, homologous to human ATGL). The high wasting in LDs shortens the lifespan of flies with high-energy-cost immune hyperactivation. Therefore, these results suggest a critical function of LDs during long-term immune activation and provide a potential treatment for the resolution of persistent inflammation.

脂滴（Lipid droplets, LDs）是一类高度动态的细胞内细胞器，参与众多生物学过程。然而，在持续性天然免疫应答过程中，细胞内脂滴的动态形态发生与功能仍不甚明确。本研究通过基因操作手段，在果蝇体内诱导长期系统性免疫激活，随后对果蝇脂肪体中的脂滴动态模式进行追踪观测。研究发现，作为脂滴重构核心调控因子的Plin1缺失，会在免疫过度激活初期阻断脂滴的最小化过程；而在持续性免疫激活后期，Plin1缺失可通过招募脂肪酶Brummer（Bmm，与人源ATGL同源），促进脂滴降解。脂滴的过度消耗会缩短处于高能量消耗型免疫过度激活状态的果蝇的寿命。综上，本研究结果揭示了脂滴在长期免疫激活过程中的关键功能，同时为持续性炎症的消退提供了潜在治疗策略。