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Adaptive modification of lipid droplets mediated by Plin1 functions in infection-induced pathogenesis in Drosophila

By Lei Wang, Jiaxin Lin, Junjing Yu, Zhiqin Fan, Hong Tang, Lei Pan

Posted 01 May 2020
bioRxiv DOI: 10.1101/2020.04.30.070292

Lipid droplets (LDs) are dynamic intracellular organelles critical for lipid metabolism. Alterations in the dynamics and functions of LDs during innate immune response to infections and the underlying mechanisms however, remain largely unknown. Herein, we describe the morphological dynamics of LDs in fat body of Drosophila, which vary between transient and sustained bacterial infections. Detailed analysis shows that perilipin1 (plin1), a core gene regulating lipid metabolism of LDs is suppressed by IMD/Relish, an innate immune signaling pathway via Martik (MRT) /Putzig (PZG) complex. During transient immune activation, downregulated plin1 promotes the formation of large LDs, which alleviates immune reaction-induced reactive oxygen species (ROS) stress. Thus, the growth of LDs is likely an active adaptation to maintain redox homeostasis in response to IMD activation. Whereas, under sustained inflammatory conditions, plin1 deficiency accelerates excessive decomposition of large LDs through recruitment of Brummer/ATGL lipase resulting in energy wasting, severe lipotoxicity and then deteriorated pathogenesis. Taken together, our study provides evidence that plin1 has a dual function on LDs'morphology in regulating infection-induced pathogenesis, and Plin1 might be a potential therapeutic target for coordinating inflammation resolution and lipid metabolism. ### Competing Interest Statement The authors have declared no competing interest.

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