# High fat diet induced remodeling of preproglucagon neuronal control of feeding behavior

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2021 · $30,776

## Abstract

PROJECT SUMMARY
Access to calorie dense, palatable foods has promoted an obesity epidemic. While much research has focused
on investigating how molecular mechanisms may be dysregulated in the already obese state, little is known
about the early events that occur upon exposure to obesogenic diets and how this may ultimately contribute to
the progression towards obesity. Studies conducted by our group and others evaluating the consequences of
access to high-fat diet (HFD) in rodents has shown time dependent alterations in feeding patterns. Specifically,
following exposure to a HFD rodents experience a transient period of hyperphagia (24-48 hours) followed by a
return to normophagia (by 72 hours) and then a subsequent gradual return to excessive caloric consumption
over a period of weeks. Elucidating the mechanisms that regulate the different feeding patterns evident during
the early stages of exposure to a HFD and prior to obesity can identify important molecular targets that may be
leveraged for either preventative or interventional therapeutics against obesity. This application aims to
assess the extent to which HFD exposure modifies interactions between vagal afferent neurons (VANs)
and hindbrain preproglucagon (PPG) neurons in the control of feeding behavior. VANs play a critical role
in relaying satiety and other food-intake related signaling from the periphery to the central nervous system
(CNS). PPG-neurons in the nucleus tractus solitarius (NTS) are the main source of Glucagon-like peptide-1
(GLP-1) in the CNS, and GLP-1 is a satiety factor that reduces caloric intake via actions on a GLP1-receptor
(GLP1R) in the CNS. The fact that VANs directly innervate NTS PPG neurons suggests that this is a key
interaction regulating feeding behavior. However, the influence of HFD on VAN-PPG neuron interactions and
subsequent effects on the control of food intake have not been established. Experiment 1 aims to evaluate the
time dependent effects of high-fat diet administration on VAN-PPG interactions in the hindbrain and tests the
hypothesis that decreases in VAN-PPG neuronal apposition are associated with hyperphagic responses to
HFD. Experiment 2 proposes to specifically characterize the influence of PPG neurons on feeding patterns
following HFD administration through selective ablation/inhibition of NTS PPG neurons. We hypothesize that
the loss/inhibition of NTS PPG neurons will exacerbate the hyperphagia associated with HFD administration
and increase the time to return to normophagia. The experiments proposed within this research application will
allow for me to gain valuable research training and experience using state of the art experimental techniques
and will strengthen my ability to function as an independent research scientist.

## Key facts

- **NIH application ID:** 10232824
- **Project number:** 1F31DK127728-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Payam Fathi
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $30,776
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232824

## Citation

> US National Institutes of Health, RePORTER application 10232824, High fat diet induced remodeling of preproglucagon neuronal control of feeding behavior (1F31DK127728-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10232824. Licensed CC0.

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