# Serotonergic modulation of the central Glucagon-like peptide-1 system regulates energy balance and stress

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2020 · $32,690

## Abstract

Project Summary
Metabolic disease and stress-related disorders have long been known to exhibit significant comorbidity. Given
the clinical relevance of both obesity and stress-related disorders, understanding the mechanisms and
identifying specific neural substrates that mediate the interaction between energy balance and stress is
essential to develop more effective treatments for these diseases. The overlap in neural circuitry governing
energy balance and stress-related physiological and behavioral responses plays a significant role in mediating
the high degree of comorbidity between obesity and stress. Efforts to understand the relationship between
energy balance and stress have primarily centered on the activation of common downstream neuroendocrine
circuitry (e.g. hypothalamic pituitary adrenal [HPA] axis) however, much less is known about the common
upstream neurobiological substrates. Serotonin (5-HT) and the central glucagon-like peptide-1 (GLP-1)
system, both of which are involved in the control of stress and energy balance, have been shown to interact at
the cellular/molecular level. The mechanism, as well as the physiological/behavioral effects of this interaction
remain to be determined and will be the focus of this proposal. Preliminary data show that the food intake
suppressive effects of hindbrain 5-HT is dependent on central GLP-1 signaling and that this effect is, at least in
part, mediated through the activation of the 5-HT2C and 5-HT3 receptors. These data indicate that the
interaction between 5-HT and central GLP-1 is relevant for the physiological effects on food intake regulation.
This application will therefore test the hypothesis that 5-HT acts as an endogenous modulator of the central
GLP-1 system and that satiation signaling and stress-induced hypophagia are both controlled by 5-HT
mediated activation of the GLP-1 system. The proposed aims will (Aim 1) assess the presence of 5-HTRs
on PPG neurons and explore the behavioral mechanism(s) through which 5-HT activation of the central GLP-1
system suppresses food intake, (Aim 2) determine the physiological relevance of the central GLP-1 system in
mediating the intake suppression induced by feeding, stress, and 5-HT, and (Aim 3) explore potential central
sources of 5-HT input onto NTS PPG neurons, as well as downstream nuclei to which these 5-HT-activated
PPG neurons project. Together, the proposed aims will help broaden our understanding of the interaction
between 5-HT and GLP-1 and highlight its importance in the regulation of energy balance.

## Key facts

- **NIH application ID:** 9977177
- **Project number:** 5F31DK118816-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Rosa Leon
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,690
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977177

## Citation

> US National Institutes of Health, RePORTER application 9977177, Serotonergic modulation of the central Glucagon-like peptide-1 system regulates energy balance and stress (5F31DK118816-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9977177. Licensed CC0.

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