Direct interoceptive input to the insular cortex shapes learned feeding behavior

2025 · doi:10.1101/2025.05.13.653896
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This study identified insular leptin receptor-positive neurons that directly sense internal states to shape learned feeding behavior and body weight regulation.

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⚙ AI-generated deep summary by claude@2026-07, 2026-07-15 · read from full text ⓘ

The study examined how the insular cortex receives direct interoceptive input to shape learned feeding behavior by identifying leptin receptor-positive neurons in the insula (INSLepR) with a distinct morphology. Using intra-insula leptin administration and optogenetic stimulation of INSLepR neurons, the authors found that manipulating these cells alters feeding behavior, and that INSLepR activity encodes feeding bouts in a manner dependent on internal state, with leptin also changing insula neural dynamics and reshaping the transcriptome in response to feeding. The authors present these results as supporting a model in which INSLepR neurons integrate adiposity-related signals to regulate food intake and body weight in a learned manner, with the main caveat being that the work is centered on leptin/adiposity interoception rather than other internal state signals. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

SUMMARY The insular cortex (insula) is an interoceptive hub, which senses internal states such as hunger, thirst, pain, and emotions. Previous studies suggest that the insula directly senses internal states, but the mechanisms remain elusive. We identified a population of leptin receptor-positive cells with a unique morphology in the insula (INS LepR ). Based on leptin’s known role in signaling adiposity, we hypothesized that INS LepR neurons detect internal states to regulate food intake and body weight. Accordingly, we found that intra-insula leptin administration or optogenetic stimulation of INS LepR neurons impacts feeding behavior. Moreover, INS LepR neuron activity encodes feeding bouts in an internal-state dependent manner, and leptin alters insula neural dynamics in response to feeding, while also reshaping the transcriptome. Taken together, our data supports a model for direct interoceptive input to the insula, in which INS LepR cells integrate adiposity level signals to regulate feeding and body weight in a learned manner.
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SUMMARY The insular cortex (insula) is an interoceptive hub, which senses internal states such as hunger, thirst, pain, and emotions. Previous studies suggest that the insula directly senses internal states, but the mechanisms remain elusive. We identified a population of leptin receptor-positive cells with a unique morphology in the insula (INSLepR). Based on leptin’s known role in signaling adiposity, we hypothesized that INSLepR neurons detect internal states to regulate food intake and body weight. Accordingly, we found that intra-insula leptin administration or optogenetic stimulation of INSLepR neurons impacts feeding behavior. Moreover, INSLepR neuron activity encodes feeding bouts in an internal-state dependent manner, and leptin alters insula neural dynamics in response to feeding, while also reshaping the transcriptome. Taken together, our data supports a model for direct interoceptive input to the insula, in which INSLepR cells integrate adiposity level signals to regulate feeding and body weight in a learned manner. Competing Interest Statement The authors have declared no competing interest. Footnotes ↵* Lead Contact;

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last seen: 2026-05-20T01:45:00.602351+00:00