# Neuroendocrine Integration of Satiety and Food Reward

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 2020 · $474,767

## Abstract

Overconsumption of highly palatable calorically dense food is a major contributor to obesity and related
metabolic disorders. This proposal investigates one of the neuropeptide systems thought to underlie neural
integration of the rewarding value of food with input from gut-derived satiety signals, Glucagon-like peptide 1
(GLP-1). Preproglucagon (PPG, the precursor to GLP-1) neurons project to many brain areas where activation
of GLP-1 receptors (GLP-1R) promotes satiety and reduces motivation for food. Most research has focused on
one or another individual PPG neuron projection and GLP-1R population at a time, and although this has
informed us about brain GLP-1 action, this approach does not provide broad insight into the functional
organization of the central GLP-1 network. Here we will take advantage of transgenic mouse models to
investigate GLP-1R neuron projections that mediate behavioral effects. We hypothesize that: 1) activation of
some, and inhibition of other GLP-1R neuron projections reduce feeding; 2) that GLP-1R neurons in different
brain nuclei receive synaptic input from unique brain regions; and 3) that GLP-1R neurons communicate with
one another across brain regions. Based on our data implicating GLP-1R neurons of the Lateral Septum (LS)
and Bed Nucleus of the Stria Terminalis (BNST) in feeding control, we focus on two exemplar cell populations:
the LS GLP-1R neuron projection to Lateral Hypothalamus (LH); and the BNST GLP-1R neuron projection to
the LH. Aim 1 focuses on the GLP-1R LS-to-LH pathway, which we hypothesize promotes satiety and
suppresses food reward when activated. Aim 2 examines the GLP-1R BNST-to-LH projection, which we
hypothesize works in the opposite direction, such that inhibition of these neurons promotes satiety and
suppresses food reward. Experiments will test these hypotheses using a combination of cell type-specific
chemogenetic and pharmacologic approaches to manipulate the activity of each of these GLP-1R neuron
projections to LH. We will conduct detailed behavioral analyses to distinguish effects on satiation, satiety,
motivation, and stress or malaise that can alter feeding, and we will use slice electrophysiology to characterize
the underlying neuronal signaling pathways. Aim 3 will determine sources of synaptic input to GLP-1R neurons
in each location, testing the hypothesis that they receive distinct sources of input from PPG and other neurons,
including GLP-1R+ neurons in other nuclei. Studies in this aim will apply a combination of traditional retrograde
tracing and cutting edge cell type- and anatomic pathway-specific mono- and transsynaptic viral tracing
methods. Together, our results will elucidate new mechanisms for GLP-1's hypophagic effects, identify new
cell type-specific neuronal pathways that play a role in brain control of feeding, and provide a more complete
picture of how PPG neurons and GLP-1-receptive cells throughout the brain coordinate to influence behavior.
We propose that centr...

## Key facts

- **NIH application ID:** 9872158
- **Project number:** 5R01DK095757-07
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Diana L Williams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $474,767
- **Award type:** 5
- **Project period:** 2013-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872158

## Citation

> US National Institutes of Health, RePORTER application 9872158, Neuroendocrine Integration of Satiety and Food Reward (5R01DK095757-07). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9872158. Licensed CC0.

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