# Astrocytes mediate GLP-1 effects on energy balance

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $547,286

## Abstract

Project Summary:
The proposed research focuses on the role of astrocytes in the Nucleus Tractus Solitarius (NTS) of the caudal
brainstem in mediating the food intake and body weight suppressive effects of glucagon-like peptide-1 (GLP-1).
Accumulating evidence indicates that the food intake suppressive effects of GLP-1 receptor (GLP-1R) agonists
(exendin-4 and liraglutide, FDA-approved for the treatment of diabetes and obesity) are mediated, in part,
through direct GLP-1R signaling in the CNS. However, the specific GLP-1R-expressing nuclei and cellular
mechanisms within the CNS that mediate the metabolic effects of GLP-1R ligands remain largely unknown.
While the collective literature clearly supports a role for neuronal processing in mediating GLP-1's effects on
food intake, the contribution of GLP-1R signaling on astrocytes to energy balance control has not been
examined. Given that astrocytes are critical for the modulation of glutamate in the extracellular space via the
GLAST and GLT-1 transporters, it is intriguing to consider the idea that GLP-1R ligands act directly on
astrocytes in energy balance relevant nuclei that receive glutamatergic inputs. The NTS is the first central
nucleus to receive and process within-meal vagally-mediated glutamatergic satiation signals arising from the
gastrointestinal tract. Therefore, building on our exciting preliminary studies, research proposed in this
application will directly test the hypothesis that GLP-1R signaling in astrocytes within the NTS is physiologically
and pharmacologically relevant for the regulation of food intake. Using state-of-the-art, cutting-edge technology
and methodological approaches we will examine the following Specific Aims: [1] Determine in vivo the
physiological relevance of GLP-1R signaling on NTS astrocytes in energy balance control. [2] Examine GLP-1R
signaling on NTS astrocytes as a modulator of vagal-to-NTS glutamatergic neurotransmission using live cell Ca++
imaging and in vivo electrophysiology. [3] Examine the intracellular signaling and cytokine responses following
GLP-1R activation of NTS astrocytes. The research proposed will provide a novel framework for a new wave of
research aimed at elucidating the role that GLP-1-astrocyte signaling plays in regulating energy balance.

## Key facts

- **NIH application ID:** 10437810
- **Project number:** 5R01DK115762-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MATTHEW R HAYES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $547,286
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437810

## Citation

> US National Institutes of Health, RePORTER application 10437810, Astrocytes mediate GLP-1 effects on energy balance (5R01DK115762-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10437810. Licensed CC0.

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