Cover Story Current Issue

Glucose is a ubiquitous and essential source of energy for all living organisms. Although mammals have evolved ways to convert other nutritional molecules to ATP, the preference for dietary glucose appears to be preserved. In rodents, the immediate detection of ingested glucose potently reinforces intake, hierarchically organizing behaviors towards glucose-yielding substances, and away from other types of food including other sugars. Taste is the primary sense linked to nutrient selection. Until recently, it was thought that most mammalian species utilize a single broadly tuned receptor to detect all simple sugars. Indeed, this “sweet” receptor, which comprises a heterodimer of the T1R2 and T1R3 proteins, binds multiple natural sugars (e.g., glucose, fructose, sucrose, maltose), as well as various other chemicals that yield little to no energy (e.g., low calorie sweeteners, sugar alcohols) and some d-amino acids. The neural signal originating from the sweet receptor is hardwired into brain circuits that drive eating and drinking behaviors, but it is an unreliable indicator of nutrient quality and quantity.

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Current Issue

Vagal Sensory Neurons Encode Internal Protein Status to Guide Eating

M. Yang, A. de Araujo, J. Shakir, I. Braga, ... G. de Lartigue

Animals adaptively adjust nutrient intake based on internal physiological need. Although protein deficiency elicits robust behavioral and endocrine responses, the sensory mechanisms that detect dietary protein and guide selective feeding remain incompletely understood. Here, we identify a population of vagal sensory neurons that respond selectively to intragastric protein and are required for adaptive regulation of protein intake. Using activity-dependent genetic labeling and in vivo calcium imaging, we show that these neurons are activated by dietary protein, exhibit enhanced responses in protein-restricted states, and are distinct from previously characterized calorie-sensing populations. Selective ablation of protein-responsive vagal neurons abolishes the normal shift in protein preference during protein deprivation, blunts motivation to work for protein rewards, and prevents behavioral updating following protein repletion. These neurons also mediate protein-specific satiety, limiting further protein intake without affecting carbohydrate consumption. Notably, protein preference is suppressed under mild caloric restriction, indicating that caloric and amino acid needs are hierarchically organized and likely monitored by separate interoceptive systems. Our findings reveal a novel vagal circuit that integrates internal protein status with nutrient-specific cues to guide adaptive protein appetite and maintain amino acid homeostasis.

 

Articles in Press

Vagal Sensory Neurons Encode Internal Protein Status to Guide Eating

M. Yang, A. de Araujo, J. Shakir, I. Braga, ... G. de Lartigue

Animals adaptively adjust nutrient intake based on internal physiological need. Although protein deficiency elicits robust behavioral and endocrine responses, the sensory mechanisms that detect dietary protein and guide selective feeding remain incompletely understood. Here, we identify a population of vagal sensory neurons that respond selectively to intragastric protein and are required for adaptive regulation of protein intake. Using activity-dependent genetic labeling and in vivo calcium imaging, we show that these neurons are activated by dietary protein, exhibit enhanced responses in protein-restricted states, and are distinct from previously characterized calorie-sensing populations. Selective ablation of protein-responsive vagal neurons abolishes the normal shift in protein preference during protein deprivation, blunts motivation to work for protein rewards, and prevents behavioral updating following protein repletion. These neurons also mediate protein-specific satiety, limiting further protein intake without affecting carbohydrate consumption. Notably, protein preference is suppressed under mild caloric restriction, indicating that caloric and amino acid needs are hierarchically organized and likely monitored by separate interoceptive systems. Our findings reveal a novel vagal circuit that integrates internal protein status with nutrient-specific cues to guide adaptive protein appetite and maintain amino acid homeostasis.

 

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You are what you eat

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