Glycogen Metabolism Drives Sensory Activation of Pomc Neurons

In this study, we aimed at uncovering the molecular mechanisms underlying POMC neuron sensory activation and the mediated behavioral and metabolic processes. Unexpectedly, we found that glycogen metabolism is rapidly engaged in POMC neurons upon sensory food perception. Genetic deletion of glycogen synthase, the sole enzyme able to make glycogen in vivo, in POMC neurons impedes food-related sensory activation while causing impairments in food awareness, short-term food intake and insulin release. These perturbations associate with whole-body metabolic defects, including overweight and insulin resistance, that are exacerbated by high-dense diets or ageing. Collectively, our study identifies glycogen metabolism as an unanticipated mechanistic driver of POMC neuron sensory activation and provides paradigm-shift evidences of the importance of neuronal glycogen for physiology. POMCRiboTag mice were exposed to either an inaccessible nonedible object (NEO; wooden dowel pins in a wire mesh) or to sensory detection of food (SENS; standard chow in a wire mesh so that it could be seen and smelled but not consumed) for 10 minutes. The transcripts recruited to ribosomes specifically in POMC neurons were profiled through RNASeq.