# The neurotransmitter for calorie

> **NIH NIH F32** · DUKE UNIVERSITY · 2022 · $74,434

## Abstract

PROJECT SUMMARY/ABSTRACT
The main motivation to feed is to obtain energy from nutrients. Thus, the maintenance of body weight depends
upon circuits which recognize the value of nutrients to guide food intake. The sensory cell of the gut, the
enteroendocrine cell, communicates to the brain via hormones to regulate food intake over tens of minutes to
hours. In 2018, we discovered that a subset of enteroendocrine cells make synaptic contact with the vagus
nerve. We named these synpatically connected cells neuropod cells. Neuropod cells communicate the
presence of carbohydrate in the duodenum to the vagus nerve within 60 milliseconds using glutamate
neurotransmission. However, the information encoded by glutamate is unknown. This application tests the
hypothesis that glutamate neurotransmission from gut to the vagus nerve encodes the energy value of
nutrients. This hypothesis will be tested in two specific aims. Specific Aim 1 will use organoid (“mini gut”) and
enteroendocrine cell culture from mice to examine glutamate release in response to nutrient stimulation. We
hypothesize that glutamate released from enteroendocrine cells encodes nutrient value, based upon the unit
energy provided by the nutrient (i.e, kilocalorie) rather than the macronutrient content. Therefore, we predict
that glutamate will be released in a kilocalorie-dependent, rather than a macronutrient-dependent manner.
Specific Aim 2 will use in vivo multiphoton calcium imaging of the vagal nodose ganglia in transgenic mice
which express the calcium indicator GCaMP6s in vagal nodose neurons. Single cell resolution of vagal neuron
activity will be recorded in response to nutrient delivery to the duodenum. If neuropod cell glutamate release
conveys information specific about energy value, rather than macronutrient content, then separate
macronutrients of equal caloric value should stimulate overlapping vagal neuron populations. By defining the
functional relevance for rapid gut-to-vagus glutamatergic signaling, these studies will provide new fundamental
biology of gut-brain communication. This work will contribute new possible avenues of pharmacotherapies for
the treatment of nutrient-intake related disease, namely obesity.

## Key facts

- **NIH application ID:** 10448263
- **Project number:** 5F32DK127757-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Laura Eloise Rupprecht
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $74,434
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448263

## Citation

> US National Institutes of Health, RePORTER application 10448263, The neurotransmitter for calorie (5F32DK127757-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10448263. Licensed CC0.

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