(P04-033-25) A Gut Sense for Amino Acids

Objectives: Dietary protein is essential for life. When protein content of food is low, individuals consume more food to achieve adequate protein intake. However, how dietary protein is sensed remains ill defined. As protein is first absorbed in the small intestine, this study aimed to evaluate the role of the gut sensory system in driving protein-seeking behavior.

Methods: To determine the effect of protein depletion on protein-seeking behavior, wild-type and genetically taste-blind mice were exposed to protein-complete or protein-deplete diets followed by a two-bottle assay, evaluating the preference for an amino acid solution. Using qPCR, we identified a unique population of cells in the small intestine that are specifically altered by protein deprivation called neuropod cells. To investigate further, we used calcium imaging to test the activity of these cells in response to essential amino acids in protein-complete and -deplete states.

Results: Protein-deficient mice demonstrated a strong preference for amino acid solution over either vehicle or glucose solutions, demonstrating the desire to consume protein independent of caloric content. This effect persisted in taste-blind mice, indicating that protein-seeking behavior is driven by the gut. Amino acid deprivation upregulated the transcripts for several putative amino acid transporters in neuropod cells. In neuropod cells, the calcium activity to several amino acids, including lysine and leucine, was increased only when the cells were deprived of protein.

Conclusions: In states of protein deficiency, neuropod cells guide seeking for protein by specific changes in transporter expression. This study identified a gut sensory mechanism involved in protein appetite, offering insights for novel treatments to combat protein malnutrition and nutritional imbalances.

Funding Sources: NIH F30DK127650, DP2MH122402, R01DK131112