Researchers describe a molecular mechanism by which sensory cues trigger a preparatory metabolic response before eating. Smells or sights of food activate pro-opiomelanocortin (POMC) neurons in the hypothalamus. The new work shows that small pockets of glycogen inside these neurons provide the energy for anticipatory activity, and that food exposure activates glycogen synthase, the enzyme that builds glycogen.
To study sensory activation, the team presented mice with food behind a wire mesh so the animals could see and smell but not eat it. Mice engineered without glycogen synthase in POMC neurons had weaker behavioural and metabolic responses: they were less likely to approach food, they spent less time eating, and they failed to produce insulin before feeding. Injecting a virus to remove the enzyme in adult mice produced similar effects, indicating the deficit was not a developmental problem.
Mapping of neural connections showed POMC neurons link with brain regions that process smell but not vision. The findings challenge the idea that brain glycogen sits mainly in astrocytes and suggest neuronal glycogen has a wider role in feeding circuits. Over time, mutant mice developed obesity and signs of prediabetes, and the authors suggest these anticipatory defects could help drive obesity and diabetes and point to new therapeutic approaches.
- Study published in Nature Metabolism
- Research supports links between brain sensing and metabolism
- Findings may inform future treatments
Difficult words
- hypothalamus — brain region that controls hunger and body functions
- glycogen — stored carbohydrate used by cells for energy
- glycogen synthase — enzyme that builds stored carbohydrate called glycogen
- astrocyte — a type of non-neuronal brain support cellastrocytes
- anticipatory — happening before an expected event
- metabolic — relating to the body's chemical energy processes
- prediabetes — condition with higher than normal blood sugar levels
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Discussion questions
- How might defects in anticipatory sensory responses contribute to long-term obesity and prediabetes? Give reasons based on the article.
- What potential advantages and risks could come from developing treatments that target glycogen synthase in neurons?
- The study challenges the idea that brain glycogen sits mainly in astrocytes. How could this change future research or treatment approaches for metabolic disorders?
