# Project 3: Neural mediators in the metabolic effects of Vertical Sleeve Gastrectomy

> **NIH NIH P01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $457,090

## Abstract

Neural mediators of the metabolic effects of vertical sleeve gastrectomy
Abstract
Decisions about what and how much to eat are regulated by a complex communication network between the
CNS and gut and involve a variety of hormonal, metabolite, and neuronal feedback systems. Bariatric surgery,
arguably the most effective treatment for obesity and its complications, alters every aspect of these feedback
systems and results in substantial weight loss and metabolic improvements. We have demonstrated that
nutrient-induced neuronal activation (FOS) is greater within a specific subset of neurons (calcitonin receptor;
CALCR) within the nucleus of the solitary tract (NTS), a CNS region that is critical for integrating peripheral
signals and initiating changes in feeding behavior, after a particular bariatric surgery, vertical sleeve
gastrectomy (VSG). VSG, a procedure where 80% of the stomach along the greater curvature is removed,
generates several potential chemo- and mechano-sensing signals that these neurons respond to including the
levels of nutrients themselves, greater gastric pressure, or the several-fold increase in many postprandial gut-
secreted peptides. The overall aim of this proposal is to determine the identity and function of these activated
NTS neurons and the mechanism(s) by which these neuronal populations are activated.
In projects 1&2 of this program project, we have generated preliminary data demonstrating that distinct
populations of neurons within the NTS (LEPRb, CALCR, and CCK) and PBN (GLP-1R and CGRP) are critical
for regulation of feeding and responses to toxins as measured by conditioned taste aversion. Given that our
data also demonstrates that CALCR within the NTS are specifically activated by VSG, our over-arching
hypothesis is that obesity impairs, and bariatric surgery “fixes” these circuits to reduce feeding and
induce weight loss. To test this hypothesis, we will use genetic and chemogenetic strategies in combination
with electrophysiology (using the neural physiology core, NPC, Goforth) to determine the relevant circuits
within the NTS (Aim 1) responsible for changes in feeding behavior with obesity and after bariatric surgery, and
in Aim 2, we will define the mechanisms that underlie the surgery-induced NTS activation.

## Key facts

- **NIH application ID:** 10454940
- **Project number:** 5P01DK117821-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** DARLEEN A. SANDOVAL
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $457,090
- **Award type:** 5
- **Project period:** 2019-09-20 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454940

## Citation

> US National Institutes of Health, RePORTER application 10454940, Project 3: Neural mediators in the metabolic effects of Vertical Sleeve Gastrectomy (5P01DK117821-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10454940. Licensed CC0.

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