# Neural hierarchy in the modulation of ingestive behavior

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $528,980

## Abstract

Project Summary:
The proposed research of this R01 application focuses on the neuropeptide glucagon-like peptide-1 (GLP-1)
and its physiological role in controlling for food intake and body weight through distributed action in the central
nervous system (CNS). This application supports the view that the central GLP-1 system is a master regulator
of many physiological and behavioral processes involved in glycemic and food intake control. Given the
growing worldwide prevalence of type II diabetes mellitus (T2DM) and obesity, it is not surprising that multiple
GLP-1-based pharmaceutics are FDA approved. As anti-obesity agents however, current GLP-1-based drugs
have limited efficacy. On average they produce ~5% weight loss through mechanisms resulting in inhibitory
actions on food intake. This proposal advocates for the perspective that to achieve greater anti-obesity efficacy
it will be necessary for basic research to decipher: (a) the specific CNS nuclei and mechanism(s) mediating
GLP-1's effects on energy balance, (b) the interactions between GLP-1 receptor (GLP-1R) signaling and
within-meal gastrointestinal satiation signals that also contribute to food intake control, as well as (c) what
impact obesity itself has on the endogenous CNS GLP-1 system in regards to energy balance regulation. To
this end, this application proposes a novel set of experiments to test the hypothesis that the distributed
neuroanatomical projections of GLP-1-producing neurons in the nucleus tractus solitarius (NTS)
simultaneously activate GLP-1 receptors at multiple energy balance relevant nuclei resulting in the
amplification of the neural processing of other satiation signals processed at these sites. Further, given that
obesity can down-regulate neuroendocrine systems involved in energy balance regulation, we will evaluate
whether the obese state negatively impacts the role of the central GLP-1 system to amplify satiety signaling.
The following specific aims are examined: [1] To examine the hypothesis that the central GLP-1 system
functions as a behavioral end-break for ongoing meal taking through simultaneous activation of anatomically
distributed GLP-1R-expressing energy balance relevant nuclei; and [2] To examine the hypothesis that obesity
down-regulates the endogenous central GLP-1 system thereby promoting the feeding behaviors that sustain
the obese state.

## Key facts

- **NIH application ID:** 10116366
- **Project number:** 5R01DK021397-42
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** HARVEY J GRILL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $528,980
- **Award type:** 5
- **Project period:** 1983-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116366

## Citation

> US National Institutes of Health, RePORTER application 10116366, Neural hierarchy in the modulation of ingestive behavior (5R01DK021397-42). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10116366. Licensed CC0.

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