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Nutrient sensing in the nucleus of the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons.

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Tsang, Anthony H 
Nuzzaci, Danae 
Darwish, Tamana 
Samudrala, Havish 
Blouet, Clémence 


UNLABELLED: The nucleus of the solitary tract (NTS) is emerging as a major site of action for the appetite-suppressive effects of leading pharmacotherapies currently investigated to treat obesity. However, our understanding of how NTS neurons regulate appetite remains incomplete. OBJECTIVES: In this study, we used NTS nutrient sensing as an entry point to characterize stimulus-defined neuronal ensembles engaged by the NTS to produce physiological satiety. METHODS: We combined histological analysis, neuroanatomical assessment using inducible viral tracing tools, and functional tests to characterize hindbrain-forebrain circuits engaged by NTS leucine sensing to suppress hunger. RESULTS: We found that NTS detection of leucine engages NTS prolactin-releasing peptide (PrRP) neurons to inhibit AgRP neurons via a population of leptin receptor-expressing neurons in the dorsomedial hypothalamus. This circuit is necessary for the anorectic response to NTS leucine, the appetite-suppressive effect of high-protein diets, and the long-term control of energy balance. CONCLUSIONS: These results extend the integrative capability of AgRP neurons to include brainstem nutrient sensing inputs.



AgRP neurons, Appetite, Hypothalamus, Metabolic diseases, Nucleus of the solitary tract, Obesity, Agouti-Related Protein, Animals, Appetite, Appetite Regulation, Brain, Energy Metabolism, Feeding Behavior, Hypothalamus, Leptin, Leucine, Male, Mice, Mice, Inbred C57BL, Neurons, Obesity, Solitary Nucleus

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Mol Metab

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Elsevier BV
Wellcome Trust (100574/Z/12/Z)
Medical Research Council (MR/N003276/1)
Wellcome Trust (204845/Z/16/Z)
Medical Research Council (MC_UU_12012/5)
MRC (MC_UU_00014/6)
MRC (MC_UU_00014/5)
MRC (MR/M501736/1)
Medical Research Council (MC_PC_12012)