Journal of Innate Immunity (Sep 2023)

Perilipin 1 Deficiency Prompts Lipolysis in Lipid Droplets and Aggravates the Pathogenesis of Persistent Immune Activation in Drosophila

  • Lei Wang,
  • Jiaxin Lin,
  • Kaiyan Yang,
  • Weina Wang,
  • Yan Lv,
  • Xiangkang Zeng,
  • Yaya Zhao,
  • Junjing Yu,
  • Lei Pan

DOI
https://doi.org/10.1159/000534099
Journal volume & issue
Vol. 15, no. 1
pp. 697 – 708

Abstract

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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.

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