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<p>Hypothalamic POMC neurons modulate systemic energy balance and glucose homeostasis by sensing nutritional state signals. In addition to this classic regulatory mode, these neurons are also activated by the sensory perception of food. Here, we report that food-related sensory cues engage glycogen metabolism in POMC neurons. Genetic depletion of glycogen through various approaches renders POMC neurons unresponsive to food-associated sensory stimuli. This defective perception of food is linked to alterations in consummatory behaviour, hepatic adaptations and cephalic insulin release associated with a prediabetic phenotype that progresses into overweight and overt diabetes with a high-calorie diet or ageing. Collectively, our results posit glycogen as a decisive fuel resource for meeting the rapid and demanding energy requirements linked with sensory activation. Furthermore, our data delineate the biological function of food perception and provide support for the physiological relevance of neuronal glycogen.</p>

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Glycogen drives the sensory activation of POMC neurons

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Alicia G. Gómez-Valadés,
  • David Meseguer,
  • Luís Varela,
  • Gabriele Lienhard,
  • Uxía Fernández,
  • Andrés Vidal-Itriago,
  • Miriam Toledo,
  • Elena Eyre,
  • Berta Laudo,
  • Francisco Díaz-Castro,
  • Macarena Pozo,
  • Mehdi Boutagouga Boudjadja,
  • Júlia Fos-Domènech,
  • Pau García-Ramón,
  • Mariana Ferreira,
  • Jordi Altirriba,
  • Daniel Beiroa,
  • Bandy Chen,
  • Amanda Rodríguez-Díaz,
  • Maria Milà-Guasch,
  • Iñigo Chivite,
  • Arnaud Obri,
  • Sara Ramírez,
  • Roberta Haddad-Tóvolli,
  • Iasim Tahiri,
  • Mathew S. Gentry,
  • Giuseppe D’Agostino,
  • Rubén Nogueiras,
  • Nicolas Renier,
  • Tamas L. Horvath,
  • Joan J. Guinovart,
  • Jordi Duran,
  • Marc Schneeberger,
  • Marc Claret

摘要

Hypothalamic POMC neurons modulate systemic energy balance and glucose homeostasis by sensing nutritional state signals. In addition to this classic regulatory mode, these neurons are also activated by the sensory perception of food. Here, we report that food-related sensory cues engage glycogen metabolism in POMC neurons. Genetic depletion of glycogen through various approaches renders POMC neurons unresponsive to food-associated sensory stimuli. This defective perception of food is linked to alterations in consummatory behaviour, hepatic adaptations and cephalic insulin release associated with a prediabetic phenotype that progresses into overweight and overt diabetes with a high-calorie diet or ageing. Collectively, our results posit glycogen as a decisive fuel resource for meeting the rapid and demanding energy requirements linked with sensory activation. Furthermore, our data delineate the biological function of food perception and provide support for the physiological relevance of neuronal glycogen.