# Therapeutic potential of vagal neurostimulation to reduce food intake

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $508,751

## Abstract

Obesity affects almost 40% percent of US adults and is associated with high levels of comorbidities, including
cancer, cardiovascular disease, and diabetes. Although effective treatments with minimal side effects are
lacking, vagus nerve stimulation (VNS) can reduce body weight and suppress feeding behavior. There is little
insight, however, into its mechanism and it is unclear whether VNS effects on feeding and body weight result
from non-specific side effects, such as nausea. The current application directly addresses these issues by
assessing gastrointestinal (GI) myoelectric changes as a potential mechanism for effects of VNS on feeding
behavior, while comparing these responses to emetic activation. We plan to accomplish this by using a ferret
model, which is a gold-standard for studying emesis, vagus nerve, and GI physiology. We will test the
hypothesis that electrical stimulation of the vagus nerve can reduce food intake without triggering
indicators of nausea, such as disrupted GI myoelectric responses, retching, and vomiting. We will
complete three Aims. Aim 1: Define the individualized GI myoelectric patterns during feeding behavior using
machine learning classification. Animals will be implanted with planar electrodes attached to the GI serosal
surface from proximal gastric fundus to distal duodenum. We will use machine learning to classify GI
myoelectric patterns of meal consumption compared to emetic-related states, including those elicited by
intragastric emetine and high amplitude and frequency VNS known to trigger emesis. Aim 2: Test the efficacy
of abdominal VNS on reducing meal size without triggering disruptions of GI myoelectric responses, retching,
and emesis. Animals will be assessed for effects of abdominal VNS using a variety of stimulus parameters on
feeding behavior and multi-site GI myoelectric recordings. Aim 3: Determine the efficacy of cervical VNS in
controlling meal size without producing off-target effects (disruptions of GI myoelectric responses, retching,
emesis, changes in heart rate, or blood pressure). We will test the impact of cervical VNS parameters on
feeding behavior, GI myoelectric responses, retching, emesis, hear rate variability, and blood pressure. Our
approach is innovative because we will use machine learning classification to detect individualized GI
myoelectric response patterns in an awake free-moving animal for comparing therapeutic and off-target effects
of VNS on feeding, GI activity, emesis, and cardiovascular function. This planned research is significant
because VNS therapy can potentially provide a frontline treatment option for patients with high levels of obesity
refractory to behavioral or pharmacological therapy, which unlike other surgical interventions for weight loss,
such as gastric bypass, is potentially tunable and reversible by changing stimulation parameters, switching the
device off, or complete removal.

## Key facts

- **NIH application ID:** 9963258
- **Project number:** 5R01DK121703-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Charles Christopher Horn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $508,751
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963258

## Citation

> US National Institutes of Health, RePORTER application 9963258, Therapeutic potential of vagal neurostimulation to reduce food intake (5R01DK121703-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9963258. Licensed CC0.

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