Neuroendocrine regulation of fat metabolism by autophagy gene atg‐18 in C. elegans dauer larvae

In environments with limited food and high population density, Caenorhabditis elegans larvae may enter the dauer stage, in which metabolism is shifted to fat accumulation to allow larvae to survive for months without food. Mutations in the insulin‐like receptor gene daf‐2 force C. elegans to constitutively form dauer larva at higher temperature. It has been reported that autophagy is required for fat accumulation in daf‐2 dauer larva. However, the mechanism underlying this process remains unknown. Here, we report that autophagy gene atg‐18 acts in a cell nonautonomous manner in neurons and intestinal cells to mediate the influence of daf‐2 signaling on fat metabolism. Moreover, ATG‐18 in chemosensory neurons plays a vital role in this metabolic process. Finally, we report that neuronal ATG‐18 functions through neurotransmitters to control fat storage in daf‐2 dauers, which suggests an essential role of autophagy in the neuroendocrine regulation of fat metabolism by insulin‐like signaling.