Genetic Analysis of Feeding Behavior and Fat Storage in C. elegans
Abstract Obesity is a disorder affecting many Understanding disorders in metabolism requires the identification of molecular and neural circuits underlying energy balance. Here we investigate the coordination between feeding behavior and fat storage in response to changing environmental conditions in C. elegans. The TGF-β ligand DAF-7 is expressed in two sensory neurons and is responsive to environmental conditions such as food availability and population density. Decreases in TGF-β signaling lead to increased fat storage, decreased feeding rate, and in young animals' entry into a hibernating dauer state. Here we show that DAF-7 signals to two interneurons to regulate fat storage, feeding, and dauer formation. However, within these interneurons different molecular signals independently regulate feeding, fat storage, and dauer formation. TGF-β signaling inhibits fat storage through G-protein signaling, despite increasing feeding through the neurotransmitters tyramine and octopamine. We also identify ~20 additional C. elegans genes that regulate feeding behavior and fat storage. Taken together, this work elucidates the complex neural and molecular circuits coordinating metabolism and behavior in nutrient limiting conditions.