# INVESTIGATING THE GUT-BRAIN SIGNALING DYNAMICS REGULATING FOOD INTAKE

> **NIH NIH R00** · MONELL CHEMICAL SENSES CENTER · 2021 · $249,000

## Abstract

PROJECT SUMMARY
The recent increase in obesity is a major public health concern. Since energy balance regulation is coordinated
by communication between the gastrointestinal (GI) tract and the brain, understanding these gut-brain
interactions will enable the development of novel obesity treatments. The hypothalamus and the hindbrain are
critical brain regions that integrate information from the gut to control food intake. Here, I will leverage recent
technological advances to explore the regulation of both these brain regions in awake, behaving animals.
Within the hypothalamus, agouti-related protein (AgRP)-expressing neurons are essential for food intake
control. Activity in AgRP neurons is high during hunger and is rapidly inhibited by food. My recent work
demonstrates that AgRP neurons are primarily regulated by calorie intake, rather than sensory detection of
food, since direct gastric infusion of macronutrients into the stomach rapidly suppresses AgRP neuron activity
in vivo. Further, this effect is recapitulated by administration of GI satiation signals normally released following
food consumption. However, the mechanisms through which the gut transmits signals to AgRP neurons remain
unknown. The mentored phase (Aims I and II) of this grant will build upon my previous work by elucidating the
mechanisms through which nutrient detection in the gut leads to AgRP neuron activity reductions. Specifically,
these aims will determine whether GI signals are transmitted vagally or through direct action on the brain, and
will uncover the AgRP axon projections that transmit nutritive signals throughout the brain. Importantly, the
mentored experiments will afford me training in peripheral manipulation of the GI tract, as well as in vivo
calcium imaging of individual neurons using microendoscopy and 2-photon microscopy, expanding my
technical expertise and enabling the proposed R00 experiments. The hindbrain nucleus tractus solitarius (NTS)
is the first central site of integration of GI-derived signals from vagal afferents, and is a key signaling node that
transmits signals from the gut to higher-order brain structures such as the hypothalamus. For the independent
phase (Aims III and IV) of my grant, I have designed experiments that build upon both my graduate and
postdoctoral training to determine how different hindbrain NTS neuron populations receive signals from the GI
tract, at unprecedented levels of temporal and cellular detail. These complementary research aims combined
with the proposed career development activities will provide me with the training necessary to successfully
transition to independence, under the guidance of my mentorship team who have extensive collective
experience with neuroscience techniques and mentorship. Overall, this award will facilitate my career as an
independent investigator characterizing the role of gut-brain signaling on the in vivo activity dynamics of
feeding-relevant neurons.

## Key facts

- **NIH application ID:** 10092151
- **Project number:** 5R00DK119574-04
- **Recipient organization:** MONELL CHEMICAL SENSES CENTER
- **Principal Investigator:** Amber L Alhadeff
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2020-02-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10092151

## Citation

> US National Institutes of Health, RePORTER application 10092151, INVESTIGATING THE GUT-BRAIN SIGNALING DYNAMICS REGULATING FOOD INTAKE (5R00DK119574-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10092151. Licensed CC0.

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