Fat body phospholipid state dictates hunger-driven feeding behavior

• DOI: 10.7554/elife.80282
• Publication Date: 2022-10-06T12:05:17Z
• Authors: Kevin P Kelly; Mroj Alassaf; Camille E Sullivan; Ava E Brent; Zachary H Goldberg; Michelle E Poling; Julien Dubrulle; Akhila Rajan
• Keywords: Genetic screen

Diet-induced obesity leads to dysfunctional feeding behavior. However, the precise molecular nodes underlying diet-induced motivation dysregulation are poorly understood. The fruit fly is a simple genetic model system yet displays significant evolutionary conservation mammalian nutrient sensing and energy balance. Using longitudinal high-sugar regime in Drosophila , we sought address how changes adipocyte lipid composition regulate We observed that subjecting adult prolonged diet degrades hunger-driven response. Lipidomics analysis reveals exposure diets significantly alters whole-body phospholipid profiles. By performing systematic screen for enzymes adipocytes, identify Pect as critical regulator of feeding. rate-limiting enzyme phosphatidylethanolamine (PE) biosynthesis pathway ortholog human PCYT2. show disrupting activity only fat cells causes insulin resistance, dysregulated lipoprotein delivery brain, loss Previously studies have noted correlation between PCYT2/Pect levels clinical obesity. Now, our unbiased provide causative evidence function metabolic homeostasis. Altogether, uncovered PE homeostasis regulates hunger