Glut1 Functions in Insulin-Producing Neurons to Regulate Lipid and Carbohydrate Storage in Drosophila

Obesity remains one of the largest health problems in the world, arising from the excess storage of triglycerides (TAGs). However, the full complement of genes that are important for regulating TAG storage is not known. The <i>Glut1</i> gene encodes a <i>Drosophila</i> glucose transporter that has been identified as a potential obesity gene through genetic screening. Yet, the tissue-specific metabolic functions of Glut1 are not fully understood. Here, we characterized the role of Glut1 in the fly brain by decreasing neuronal <i>Glut1</i> levels with RNAi and measuring glycogen and TAGs. <i>Glut1RNAi</i> flies had decreased TAG and glycogen levels, suggesting a nonautonomous role of Glut1 in the fly brain to regulate nutrient storage. A group of hormones that regulate metabolism and are expressed in the fly brain are <i>Drosophila</i> insulin-like peptides (Ilps) 2, 3, and 5. Interestingly, we observed blunted <i>Ilp3</i> and <i>Ilp5</i> expression in neuronal <i>Glut1RNAi</i> flies, suggesting Glut1 functions in insulin-producing neurons (IPCs) to regulate whole-organism TAG and glycogen storage. Consistent with this hypothesis, we also saw fewer TAGs and glycogens and decreased expression of <i>Ilp3</i> and <i>Ilp5</i> in flies with IPC-specific <i>Glut1RNAi</i>. Together, these data suggest Glut1 functions as a nutrient sensor in IPCs, controlling TAG and glycogen storage and regulating systemic energy homeostasis.