The ESCRT-III Protein Regulates Lipid Storage in the Fat Body.

Defects in how excess nutrients are stored as triglycerides can result in several diseases including obesity, heart disease, and diabetes. Understanding the genes responsible for normal lipid homeostasis will help understand the pathogenesis of these diseases. RNAi screens performed in cells identified genes involved in vesicle formation and protein sorting as important for the formation of lipid droplets; however, all of the vesicular trafficking proteins that regulate lipid storage are unknown. Here, we characterize the function of the Charged multivesicular protein 1 () gene in regulating fat storage. is a member of the ESCRT-III complex that targets membrane localized signaling receptors to intralumenal vesicles in the multivesicular body of the endosome and then ultimately to the lysosome for degradation. When levels are decreased specifically in the fly fat body, triglyceride accumulates while fat-body-specific overexpression decreases triglycerides. controls triglyceride storage by regulating the number and size of fat body cells produced and not by altering food consumption or lipid metabolic enzyme gene expression. Together, these data uncover a novel function for in controlling lipid storage in and supports the role of the endomembrane system in regulating metabolic homeostasis.