PT  - JOURNAL ARTICLE
AU  - Brittany A. Martínez
AU  - Michelle L. Bland
TI  - Innate immune signaling in <em>Drosophila</em> shifts anabolic lipid metabolism from triglyceride storage to phospholipid synthesis in an ER stress dependent manner
AID  - 10.1101/2020.03.01.972208
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.01.972208
4099  - http://biorxiv.org/content/early/2020/03/03/2020.03.01.972208.short
4100  - http://biorxiv.org/content/early/2020/03/03/2020.03.01.972208.full
AB  - During infection, cellular resources are allocated toward synthesis and secretion of effector proteins that neutralize and kill invading pathogens. In Drosophila, antimicrobial peptides (AMPs) are produced in the fat body, an organ that also serves as a major nutrient storage depot. Here we asked how the innate immune response activated by fat body Toll signaling alters lipid metabolism as a model for understanding how the cellular and energetic demands of the immune response are met. We find that genetic activation of fat body Toll signaling leads to a tissue-autonomous reduction in triglyceride storage that is paralleled by decreased transcript levels of Lipin and midway, enzymes that carry out the final steps of triglyceride synthesis. In contrast, Kennedy pathway enzymes that synthesize phospholipids and their products, phosphatidylcholine and phosphatidylethanolamine, are induced in fat bodies with active Toll signaling. Induction of these enzymes depends on the unfolded protein response mediator Xbp1, and examination of endoplasmic reticulum (ER) morphology by transmission electron microscopy revealed significantly expanded ER in fat body cells with active Toll signaling. Together these results indicate that Toll signaling induces a metabolic switch from triglyceride storage to phospholipid synthesis and ER expansion; this occurs in response to AMP production and may sustain AMP synthesis and secretion during infection. Better understanding of how this anabolic switch in lipid metabolism is induced, as well as the long-term consequences of reduced triglyceride storage at the expense of phospholipid synthesis, should yield insight into metabolic diseases that stem from chronic inflammation.