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bioRxiv · 10.1101/2021.12.16.472854

Fat Body Phospholipid State Dictates Hunger Driven Feeding Behavior

Kelly, K. P.·Alassaf, M.·Sullivan, C. E.·Brent, A. E.·Goldberg, Z. H.·Poling, M. E.·Dubrulle, J.·Rajan, A.
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Abstract

Diet-induced obesity (DIO) leads to dysfunctional feeding behavior. However, the precise molecular nodes underlying diet-induced dysregulation of satiety sensing and feeding motivation are poorly understood. The fruit fly is a simple genetic model system yet displays significant evolutionary conservation to mammalian nutrient sensing and energy balance. Using a longitudinal high sugar regime in Drosophila, we sought to address how lipid alteration in fat cells alters feeding behavior. We find that prolonged exposure to HSD degrades the hunger-driven feeding (HDF) response. Lipidomics analysis reveals that longitudinal exposure to HSD significantly alters whole body phospholipid profiles. By performing a systematic screen for phospholipid enzymes, we identify Pect as a critical regulator of hunger-driven feeding. Pect is a rate-limiting enzyme in the phosphatidylethanolamine (PE) biosynthesis pathway and the fly ortholog of human PCYT2. We show that disrupting Pect only in the fat body causes insulin-resistant phenotypes and a loss of hunger-driven feeding. Excitingly, we find that overexpression of Pect restores HSD-induced loss of hunger-driven feeding response. Strikingly human studies have noted a correlation between PCYT2/Pect levels and clinical obesity. Now, our unbiased studies in Drosophila provide specific genetic evidence for Pect in maintaining nutrient sensing during DIO. Our study provides novel insights into the role of phospholipids in interorgan communication of nutrient status. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=193 SRC="FIGDIR/small/472854v4_ufigA1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@1ecf3eorg.highwire.dtl.DTLVardef@b800f2org.highwire.dtl.DTLVardef@461a7eorg.highwire.dtl.DTLVardef@75651c_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Kelly, K. P., Alassaf, M., Sullivan, C. E., Brent, A. E., Goldberg, Z. H., Poling, M. E., Dubrulle, J., Rajan, A.. 2021-12-17. Fat Body Phospholipid State Dictates Hunger Driven Feeding Behavior. https://doi.org/10.1101/2021.12.16.472854

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